Veias Varicosas

National Clinical Guideline Centre
Varicose Veins Appendices
Varicose Veins
Appendices A-O
Appendices
Methods, evidence and recommendations
12th February 2013
Draft for consultation
Commissioned by the National Institute for

Health and Clinical Excellence
DRAFT FOR CONSULTATION
Contents
Disclaimer
Healthcare professionals are expected to take NICE clinical guidelines fully into account when
exercising their clinical judgement. However, the guidance does not override the responsibility of
healthcare professionals to make decisions appropriate to the circumstances of each patient, in
consultation with the patient and/or their guardian or carer.
Copyright
Varicose Veins Full Guideline Appendices - draft (January 2013)
Funding
National Institute for Health and Clinical Excellence

Contents
Appendices .................................................................................................................................. 6
Appendix A: Scope........................................................................................................................... 6
Appendix B: Declarations of interest ............................................................................................ 14
Appendix C: Review protocols ...................................................................................................... 28
Appendix D: Clinical article selection ............................................................................................ 50
Appendix E: Economic article selection ........................................................................................ 61
Appendix F: Literature search strategies ...................................................................................... 73
Appendix G: Evidence tables clinical studies ................................................................................. 96
Appendix H: Evidence tables economic studies .......................................................................... 280
Appendix I: Forest plots ............................................................................................................. 288
Appendix J: Excluded clinical studies ......................................................................................... 329
Appendix K: Excluded economic studies ..................................................................................... 338
Appendix L: Cost-effectiveness analysis of interventional treatments and conservative care .. 340
Appendix M: Network meta-analysis ................................................................................. 370
Appendix N: Research recommendations ................................................................................... 373
Appendix O: References .............................................................................................................. 380

4

5
Scope
1 Appendices
2 Appendix A: Scope
3
4

6
Scope
1
2

7
Scope
1
2

8
Scope
1
2

9
Scope
1
2

10
Scope
1
2

11
Scope
1
2

12
Scope

13
Declarations of interest
1 Appendix B: Declarations of interest

2 B.1 Professor Alun Davies
GDG meeting Declaration of Interests Action taken
On Application AD declared he knew of no personal pecuniary No action necessary
interests, personal family interests, non-
personal pecuniary interests or personal non-
pecuniary interests in the past 12 months or
upcoming months.
First GDG None Declared None
meeting
[21/09/11]
Second GDG Personal pecuniary (non-specific): Attended No direct sponsorship by any
Meeting and lectured at Turkish Vascular society, manufacturer company involved in
[02/11/11] European Society of Vascular surgery, varicose veins related products. Funding
European Venous Forum, ARAB vein meeting not beyond that reasonably expected.
(Saudi Arabia). The meeting organisers paid NOF, KK and KH agreed no action was
expenses but no monies were given for necessary
lecturing. The organisers would have had
multiple healthcare related sponsors.
Third GDG Personal pecuniary (non-specific): Expenses No direct sponsorship by any
Meeting paid for attending and lecturing at Veith manufacturer company involved in
[14/12/11] symposium (USA). The meeting organisers varicose veins related products. Funding
paid expenses but no monies were given for not beyond that reasonably expected.
lecturing. The organisers would have had NOF, KK and KH agreed no action was
multiple industrial sponsors. necessary
Fourth GDG Personal Pecuniary (non-specific): Attended No direct sponsorship by any
Meeting academic meeting of CACVS (Controversies manufacturer company involved in
[25/01/12] and Updates in Vascular Surgery) in France varicose veins related products. Funding
and received expenses for registration, travel not beyond that reasonably expected.
and accommodation from meeting organisers, NOF, KK and KH agreed no action was
who would have had industrial sponsorship. necessary.
Non-personal pecuniary (non-specific): The grant was awarded by an academic

Research department was awarded a grant body, not involved in the manufacture
from Venous Forum UK. of varicose veins related equipment.
NOF, KK and KH agreed no action was
necessary.
Fifth GDG Personal Pecuniary (non-specific): Attended No direct sponsorship by any
Meeting American Venous Forum (USA) with manufacturer company involved in
[07/03/12] registration paid for by meeting organisers varicose veins related products. Funding
who would have had industrial sponsorship. not beyond that reasonably expected.
necessary
Non-personal pecuniary (non-specific): Met Glue is not a technology under
with Sapheon to investigate commencing a consideration in this guideline and
trial in the UK on vein ablation with a novel Sapheon do not make any other
glue technology. A grant has been awarded products used in the management of
from Sapheon to Imperial College for which AD varicose veins.
is the principle investigator. NOF, KK and KH agreed no action was
necessary.

14
Non personal pecuniary (non-specific): A The technique under investigation is not

grant was awarded to the research a technology under consideration in this
department from Clarivein (novel vibrating guideline and Clarivein do not make any
technology for varicose vein treatment), for other products used in the management
which AD is the principle investigator. of varicose veins.
necessary.
Sixth GDG Non personal pecuniary (non-specific):- A The prevention of VTE is not relevant to
Meeting grant of was awarded to the research this guideline and the Geko do not make
[18/04/12] department from Geko to fund a trial looking any other products used in the
at an electrical stimulation tool for the management of varicose veins.
prevention of VTE. NOF, KK and KH agreed no action was
necessary.
Personal pecuniary (non-specific): Organised No direct sponsorship by any

and attended major meeting (Charing Cross manufacturer company involved in
Symposium) with multiple industrial sponsors varicose veins related products. Funding
and attended meal. not beyond that reasonably expected.
necessary.
Personal pecuniary (non-specific): Received a No direct sponsorship by any

bursary to cover travel and accommodation manufacturer company involved in
expenses from Australasian College of varicose veins related products. Funding
Phlebology (ACP) to attend and lecture at their not beyond that reasonably expected.
annual meeting (Australia). The meeting NOF, KK and KH agreed no action was
organisers who would have had industrial necessary
sponsorship.
Personal pecuniary (non-specific): Attended Pharmacological treatments are under

and meeting with Servier (Paris) to discuss consideration in this guideline and
Daflon a pharmaceutical treatment of varicose Servier do not make any other products
veins. Servier paid travel expenses. used in the management of varicose
veins.
necessary.
Personal non-pecuniary (non-specific): No direct sponsorship by any

Received expenses for travel, registration and manufacturer company involved in
accommodation to the European Vascular varicose veins related products. Funding
Course (Belgium) from the meeting organisers. not beyond that reasonably expected.
The meeting organisers who would have had NOF, KK and KH agreed no action was
industrial sponsorship. necessary
Seventh GDG Did not attend this meeting No action necessary
Meeting
[11/07/12]
Eighth GDG Personal pecuniary (non-specific): Attended VASCUTEK do not make any venous
Meeting vascular meeting in India funded by the Indian products. Funding not beyond that
[03/10/12] vascular society and VASCUTEK. reasonably expected. KK and KH agreed
no action was necessary
Ninth GDG No change to declarations of interest. None

15

Meeting
[07/11/12]
Tenth GDG Personal pecuniary (non-specific): Attended VASCUTEK do not make any venous
Meeting the Veith Vascular Symposium as a guest products. Funding not beyond that
[19/12/12] speaker and gave 7 talks. Fights were funded reasonably expected. KK and KH agreed
by VASCUTEK UK and the meeting was no action was necessary
sponsored by multiple companies
Eleventh GDG
Meeting
[10/04/13]
1 B.2 Dr. Mustapha Azzam

On Application MA declared he knew of no personal No action necessary
pecuniary interests, personal family interests,
non-personal pecuniary interests or personal
non-pecuniary interests in the past 12 months
or upcoming months.
First GDG None None
meeting
[21/09/11]
Second GDG None None
Meeting
[02/11/11]
Third GDG None None
Meeting
[14/12/11]
Fourth GDG None None

Meeting
[25/01/12]
Fifth GDG Personal pecuniary (non-specific): Attended a The prevention of VTE is not relevant to
Meeting meeting with GEKO to discuss their electrical this guideline and the GEKO do not
[07/03/12] stimulation device for the prevention of DVT. make any other products used in the
management of varicose veins.
AD, NOF, KK and KH agreed no action
was necessary.
Sixth GDG Personal pecuniary (non-specific):- Attended a Sapheon do not make anything under
Meeting dinner with representatives of Sapheon. consideration in the guideline.
[18/04/12] AD, KK and KH agreed no action was
necessary.
Personal pecuniary (non-specific):Attended an First Sky Medical do not make anything

advisory board meeting with First Sky Medical under consideration in the guideline.
AD, KK and KH agreed no action was
necessary
Seventh GDG Personal pecuniary (non-specific): Assisted The prevention of VTE is not relevant to
Meeting GEKO in setting up a Doppler protocol for a this guideline and GEKO do not make

16

[11/07/12] trial of their electrical stimulation device for any other products used in the
the prevention of DVT in orthopaedic patients. management of varicose veins.
AD, KK and KH agreed no action was
necessary.
Eighth GDG No change to declarations of interest. None
Meeting
[03/10/12]

Meeting
[07/11/12]
Tenth GDG No change to declarations of interest. None

Meeting
[19/12/12]
Eleventh GDG
Meeting
[10/04/13]
2 B.3 Professor Andrew Bradbury

On Application AB declared he knew of no personal pecuniary No action necessary
upcoming months.
First GDG Did not attend this meeting None
meeting
[21/09/11]
Meeting
[02/11/11]
Third GDG Personal pecuniary (Specific): Attended as No direct sponsorship by any
Meeting part of the faculty the European Venous manufacturer company involved in
[14/12/11] Forum (EVF) Hands-On Workshop (HOW) in varicose veins related products. All
Vienna in November 2011. Travel and sponsorship not considered to be
accommodation costs were covered by the beyond what would reasonably be
EVF and those funds were obtained from a required for accommodation, meals and
range of different companies who travel to attend. AD, NOF and KK
manufacture materials and equipment used agreed no action was necessary.
for the treatment of venous disease.
Fourth GDG No change to declarations of interest. None
Meeting
[25/01/12]
Fifth GDG No change to declarations of interest. None

Meeting
[07/03/12]

17
Sixth GDG Non-personal pecuniary (Specific): No personal knowledge of the

Meeting Department did some research which was intervention or matter either through
[18/04/12] funded by British Biotechnology Group (BTG) his or her own work, or through direct
Ltd, who are trying to make a commercial supervision of other people’s work.
foam, looking at the evaluation of a novel AD, KK and KH agreed no action was
health-related quality-of-life (HRQL) required.
instrument administered via a Palmtop
Application Device (PAD). The funds were used
to pay the salary of a research nurse. No
personal payment received
Seventh GDG Personal Non-pecuniary –Had a discussion Discussed within the GDG. It was
Meeting with the Chief Executive of STD concluded that as the GDG were aware
[11/07/12] pharmaceuticals (who make a chemical called of this declaration and could take it into
STS which can be used to make foam for the consideration during the GDG meetings
treatment of varicose veins) during dinner at they did not feel that AB should be
the European Venous Forum annual meeting excluded. AB will remain in the
in Florence in June 2012. During that dinner discussion and development of
the application of a European licence for STS recommendations.
foam was discussed.
Eighth GDG Did not attend this meeting None
Meeting
[03/10/12]

Meeting
[07/11/12]
Tenth GDG Did not attend this meeting None

Meeting
[19/12/12]
Eleventh GDG
Meeting
[10/04/13]
2 B.4 Dr. Jocelyn Brookes

On Application JB declared he knew of no personal pecuniary No action necessary
upcoming months.
First GDG None None
meeting
[21/09/11]
Meeting
[02/11/11]

18

Third GDG None None
Meeting
[14/12/11]
Fourth GDG Did not attend this meeting None

Meeting
[25/01/12]
Fifth GDG None None

Meeting
[07/03/12]
Sixth GDG Did not attend this meeting None

Meeting
[18/04/12]
Seventh GDG None None

Meeting
[11/07/12]
Eighth GDG None None

Meeting
[03/10/12]
Ninth GDG Did not attend this meeting None

Meeting
[07/11/12]
Tenth GDG None None

Meeting
[19/12/12]
Eleventh GDG
Meeting
[10/04/13]
2 B.5 Mrs. Joyce Calam

On Application JC declared she knew of no personal pecuniary No action necessary
upcoming months.
First GDG None None
meeting
[21/09/11]
Meeting

19

[02/11/11]
Third GDG None None
Meeting
[14/12/11]

Meeting
[25/01/12]
Fifth GDG None None

Meeting
[07/03/12]
Sixth GDG None None

Meeting
[18/04/12]

Meeting
[11/07/12]

Meeting
[03/10/12]
Ninth GDG None None
Meeting
[07/11/12]
Tenth GDG None None
Meeting
[19/12/12]
Eleventh GDG
Meeting
[10/04/13]
2 B.6 Mr. David Evans

On Application DE declared he knew of no personal pecuniary No action necessary
upcoming months.
First GDG None None
meeting
[21/09/11]
Meeting
[02/11/11]

20

Third GDG Personal pecuniary (non-specific): I hold the As Astrazeneca nor GlaxoSmithKleine is
Meeting shares with Astrazeneca and involved in the manufacture of any
[14/12/11] GlaxoSmithKleine. products relevant to the varicose vein
guideline AD, NO’F and KK agreed that
no action is necessary.
Meeting
[25/01/12]

Meeting
[07/03/12]
Sixth GDG No change to declarations of interest. None

Meeting
[18/04/12]
Seventh GDG No change to declarations of interest. None

Meeting
[11/07/12]

Meeting
[03/10/12]

Meeting
[07/11/12]

Meeting
[19/12/12]
Eleventh GDG
Meeting
[10/04/13]
2 B.7 Mr Nick Hickey

On Application Personal pecuniary interest - I am employed No action necessary
by the NHS as a vascular surgeon, the role
includes the management of varicose veins. I
am also in private practice, including the
treatment of varicose veins.
First GDG No change to declarations of interest. None
meeting
[21/09/11]
Second GDG No change to declarations of interest. None

21

Meeting
[02/11/11]
Third GDG No change to declarations of interest. None
Meeting
[14/12/11]

Meeting
[25/01/12]

Meeting
[07/03/12]
Sixth GDG No change to declarations of interest. None

Meeting
[18/04/12]

Meeting
[11/07/12]

Meeting
[03/10/12]

Meeting
[07/11/12]

Meeting
[19/12/12]
Eleventh GDG
Meeting
[10/04/13]
2 B.8 Mr Keith Poskitt

On Application KP declared he knew of no personal pecuniary No action necessary
upcoming months.
First GDG None None
meeting
[21/09/11]

22

Meeting
[02/11/11]
Third GDG Personal pecuniary (non-specific): Attendance No direct sponsorship by any
Meeting at Veith Symposium meeting manufacturer company involved in
[14/12/11] varicose veins related products. Funding
not beyond that reasonably expected.
AD, NOF and KK agreed no action was
necessary.
Meeting
[25/01/12]
Fifth GDG Personal non pecuniary: Attended a breakfast AD, NOF and KK agreed that no action
Meeting meeting on chronic venous insufficiency at was necessary.
[07/03/12] House of Commons on 7th March 2012
Sixth GDG None None

Meeting
[18/04/12]
Seventh GDG Non personal pecuniary (specific): Received KK and KH agreed that no action was
Meeting funding from STD pharmaceuticals to support necessary.
[11/07/12] a trip by his registrar to present research in
Florence at European Venous Forum
Meeting
[03/10/12]

Meeting
[07/11/12]

Meeting
[19/12/12]
Eleventh GDG
Meeting
[10/04/13]
2 B.9 Ms. Hazel Trender

On Application HT declared she knew of no personal No action necessary
or upcoming months.

23

First GDG None None
meeting
[21/09/11]
Meeting
[02/11/11]
Third GDG None None
Meeting
[14/12/11]
Fourth GDG Personal pecuniary (specific): Personal non- Medi-UK manufactures compression
Meeting pecuniary - Sponsorship to attend Vascular stocking which may be used for varicose
[25/01/12] Society Annual meeting from Medi UK veins patients. However, funding not
beyond that reasonably expected.
necessary.

Meeting
[07/03/12]
Sixth GDG Personal pecuniary (specific): Personal non- Activa manufactures compressions
Meeting pecuniary - Funding for registration and stockings which may be used for
[18/04/12] accommodation for venous forum from Activa varicose veins patients. However,
(stocking manufacturers) funding not beyond that reasonably
expected.
necessary.

Meeting
[11/07/12]

Meeting
[03/10/12]

Meeting
[07/11/12]
Tenth GDG Personal pecuniary (specific): Sponsorship Medi-UK manufactures compression

Meeting from Medi UK to attend the Vascular Society stocking which may be used for varicose
[19/12/12] Meeting. veins patients. However, funding not
beyond that reasonably expected.
AD and KK agreed no action was
necessary.
Eleventh GDG
Meeting
[10/04/13]

24
2 B.10 Dr. Mark Vaughn

On Application MV declared he knew of no personal No action necessary
or upcoming months.
First GDG None None
meeting
[21/09/11]
Meeting
[02/11/11]
Third GDG None None
Meeting
[14/12/11]

Meeting
[25/01/12]
Fifth GDG None None

Meeting
[07/03/12]
Sixth GDG None None

Meeting
[18/04/12]

Meeting
[11/07/12]

Meeting
[03/10/12]

Meeting
[07/11/12]
Tenth GDG Personal non pecuniary: Agreed to speak at None

Meeting the National Primary Care Conference in May
[19/12/12] 2013. There have been no discussions about
payment.
Eleventh GDG None
Meeting
[10/04/13]

25
2 B.11 Expert Advisors

3 B.11.1 Dr. Christine Evans
On Application None None
4 B.11.2 Ms. Jenny Greenfield

On application None None
First GDG None None
meeting
[21/09/11]
Meeting
[02/11/11]
Third GDG None None
Meeting
[14/12/11]

Meeting
[25/01/12]
Fifth GDG None None

Meeting
[07/03/12]
Sixth GDG Did not attend None

Meeting
[18/04/12]

Meeting
[11/07/12]
Eighth GDG Did not attend this meeting None

Meeting
[03/10/12]
Ninth GDG None None

Meeting
[07/11/12]

26
1 B.11.3 Ms. Janine Elson

On application None None
Meeting
[07/11/12]

27
Review protocols
1 Appendix C: Review protocols

2 C.1 Chapter 5 – patient perceptions and expectations
3 Table 1: Review protocol: Patient perceptions and expectations
Review What are the perceptions and expectations of people with varicose veins (e.g. natural
question history, treatment) and how can they be addressed?
Objectives • To identify the perceptions and expectations of people with varicose veins with regard
to:
o Risk factors for developing varicose veins
o Progression of varicose veins
o Expectations about treatment
• To identify what information should be given to people with varicose veins in order to
manage expectations and perceptions
• To identify how information should be given
Setting Primary and secondary care
Population Adults with leg varicose veins.
Intervention NA
Comparison NA
Outcomes Any perceptions and expectations that are identified by people with varicose veins about
their condition including those before and after treatment.
How people with varicose veins would like to receive information on their condition.
Evaluation Narrative summary of findings on patient perceptions and expectations related to the
assessment, treatment, treatment success/failure, retreatment, adverse events and
disease progression of varicose veins. Studies suggesting how such expectations can be
addressed were also evaluated.
Exclusion Studies that do not specify a varicose veins population.
Opinion papers
Search The databases to be searched are Medline, Embase, The Cochrane Library, CINAHL and
strategy Psych Lit.
Studies will be restricted to English language only.
We will look for studies collecting data on patient expectations and perceptions related to
the assessment, treatment, treatment success/failure, retreatment, adverse events and
disease progression of varicose veins including risk factors for development of varicose
veins.
We will also look for studies suggesting how such expectations can be addressed.
The review Qualitative studies and questionnaire surveys will be searched
strategy If there are no published opinions on how expectations can be addressed, that part of the
question will be answered solely by GDG consensus.
Key papers Shepherd AC et al. Phlebology 2010; 25: 54-65
Darvall KA et al. Euro J Vasc Endovasc Surg 2009; 38: 642-647
Palfreyman SJ et al. J Clin Nurs 2004; 13: 332-340

28
Review protocols
1 C.2 Chapter 6 – referral to a vascular service

2 C.2.1 Factors associated with disease progression
3 Table 2: Review protocol: factors associated with disease progression

Review a. In people with leg varicose veins at CEAP class C2 which signs, symptoms and/or
question patient characteristics are associated with disease progression to i) C3, ii) C4*, iii) C6?
b. In people with leg varicose veins at CEAP class C3 which signs, symptoms and/or
patient characteristics are associated with disease progression to i) C4*, ii) C6?
c. In people with leg varicose veins at CEAP class C4* which signs, symptoms and/or
patient characteristics are associated with disease progression to C6?
* Will separate out CEAP classes C4a and C4b where evidence exists
Population Adults with leg varicose veins at CEAP stage C2 OR C3 OR C4 [as in parts a), b) and c) of the
clinical question]
Prognostic Clinical signs that can be assessed prior to referral to a vascular service:
Factors • Location/extent of varicose veins
• Any other aspects of physical examination
Clinical symptoms that can be assessed prior to referral to a vascular service:

• Severity of pain
• Severity of other varicose veins symptoms
Patient characteristics that can be assessed prior to referral to a vascular service:

• Age
• BMI
• Comorbidities
• Pregnancy/no of previous pregnancies
• Severity of pain
• Severity of other varicose veins symptoms
• Past history of deep vein thrombosis (DVT)
• Recurrent varicose veins
Outcomes Progression to the CEAP class endpoints defined by parts a), b) or c) of the clinical question
• Stratify studies with people who have previously-treated varicose veins
• Exclude studies where follow-up was less than 1 year
Search The databases to be searched are Medline, Embase, The Cochrane Library, CINAHL
strategy Studies will be restricted to English Language only
The review Where studies based on individual patient data (pooled analysis) are available, these are
strategy reviewed and other type of evidence such as meta-analysis, systematic reviews,
prospective cohorts/case-control and cross-sectional studies are not included.
Hierarchy of evidence (only go down a level if there is a lack of evidence ):
• Pooled analysis of patient level data
• Meta-analysis/systematic reviews
• Cohort Studies
• Other observational studies
Key papers Bonn vein studies, Nelson, NZ data, Framingham study
4
5

29
Review protocols
1 C.2.2 Factors associated with treatment success
2 Table 3: Review protocol: factors associated with treatment success

Review
In people with leg varicose veins are there any factors (clinical signs and symptoms or
question
patient reported outcomes) that would predict increased benefits or harms from varicose
veins interventional treatments?
Population Adults with leg varicose veins
Prognostic Clinical signs and symptoms that can be assessed prior to referral to a vascular service:
Factors • Any aspects of physical examination (CEAP)
• Patient-assessed symptoms (including pain, discomfort, cosmetic concerns/cosmesis,
swelling (oedema), aching, heaviness.)
Patient characteristics that can be assessed prior to referral to a vascular service:

• Age
• BMI
• Comorbidities
• Parity
• Recurrent varicose veins
• Medical history (including family history)
Patient reported outcomes that can be assessed prior to referral to a vascular service:
• Health-related quality of life, using generic (e.g. Medical Outcomes Study Short Form 36,
EQ-5D)
• disease specific validated tools (e.g. Chronic Venous Insufficiency Questionnaire, Aberdeen
Varicose Vein Symptom Severity Score).
Outcomes Patient-reported outcome:-
EQ-5D) and disease specific validated tools (e.g. Chronic Venous Insufficiency
Questionnaire, Aberdeen Varicose Vein Symptom Severity Score).
swelling (oedema), aching, heaviness.
Physician-reported outcomes (venous clinical severity score or venous disability score, CEAP)
Presence of reflux:
• Within 3 months
• >3–12 months
• >1–5 years
Need for additional/further treatment (i.e. compression therapy and/or ablative

techniques) over the following time periods: (same time intervals as above
• Immediate: Within 3 months post intervention
• Intermediate: >3–12 months post intervention
• Long term: >1–5 years post intervention
Adverse events from intervention (including venous thrombo-embolism [VTE], i.e.

pulmonary embolism [PE] and deep vein thrombosis (DVT); major neurological event (i.e.
stroke); local neurological events, i.e. nerve injury/damage, paraesthesia, neuralgia,
numbness; post-procedure pain; phlebitis; skin pigmentation/discolouration.

30
Review protocols
Review
In people with leg varicose veins are there any factors (clinical signs and symptoms or
question
patient reported outcomes) that would predict increased benefits or harms from varicose
veins interventional treatments?
Prevention of complications from varicose veins (leg ulcer occurrence or recurrence,

haemorrhage (bleeding) and thrombophlebitis.
Return to work/normal activities
Studies not using a multivariable analysis
Search The databases to be searched are Medline, Embase, The Cochrane Library, CINAHL
strategy Studies will be restricted to English Language only
The review Where studies based on individual patient data (pooled analysis) are available, these are
strategy reviewed and other type of evidence such as meta-analysis, systematic reviews, prospective
cohorts/case-control and cross-sectional studies are not included.
Hierarchy of evidence (only go down a level if there is a lack of literature):
• Pooled analysis of patient level data
• Meta-analysis/systematic reviews
• Cohort Studies
• Other observational studies
Analysis Stratification will occur by treatment type.
2 C.3 Chapter 7 – assessment for treatment

3 C.3.1 Diagnostic accuracy of hand held Doppler
4 Table 4: Review protocol: Diagnostic accuracy of hand held Doppler

What is the diagnostic accuracy of hand held Doppler (HHD) compared to Duplex
Review question scanning when used in patients with varicose veins?
Index tests Hand held Doppler ultrasound testing for venous reflux
Reference standard Duplex ultrasound scanning for venous reflux
Outcomes Main outcomes:
• Sensitivity (%) and specificity (%), for particular threshold(s)
• Area under the ROC curve (AUC) – measure of predictive accuracy
Other outcomes:
• Positive/negative predictive value
• Positive/ negative diagnostic likelihood ratios
• Post-test probability (at a set pre-test probability)
Search strategy The databases to be searched are Medline, Embase, The Cochrane Library, CINAHL.
Studies will be restricted to English language only.
The review strategy Diagnostic studies
Analysis We will analyse the diagnostic accuracy of hand held Doppler ultrasound.
We will note at what point in the patient pathway the study is done.
5

31
Review protocols
1 C.3.2 Assessment with duplex prior to interventional treatment
2 Table 5: Review protocol: Duplex vs. no duplex prior to interventional treatment

Does the use of duplex ultrasound during assessment improve outcome after
Review interventional treatment compared to no duplex scanning in people with leg varicose
question veins?
Intervention Duplex ultrasound assessment prior to interventional treatment (surgery, endothermal
ablation or foam sclerotherapy)
Comparison No duplex ultrasound assessment prior to interventional treatment
Questionnaire, Aberdeen Varicose Vein Symptom Severity Score)
<N.B. to use overall scores only>
swelling, aching, heaviness).
Physician-reported outcomes (venous clinical severity score or venous disability score).

<N.B. to use overall scores only>
Presence of reflux:
• Within 3 months
• >3–12 months
• >1–5 years
<N.B. if no reflux data is available, to include incomplete impartial occlusion/incomplete
stripping rates within the same analysis>

techniques) over the following time periods:
Adverse events from intervention including:

• venous thromboembolism [VTE], i.e. pulmonary embolism [PE] and deep vein thrombosis
(DVT);
• major neurological event (i.e. stroke);
• local neurological events, i.e. nerve injury/damage, paraesthesia, neuralgia, numbness;
• post-procedure pain;
• phlebitis;
• skin pigmentation/discolouration.


Studies that compare different interventions as well as the use/no use of duplex
Search The databases to be searched are Medline, Embase, The Cochrane Library, CINAHL.

32
Review protocols
Does the use of duplex ultrasound during assessment improve outcome after
Review interventional treatment compared to no duplex scanning in people with leg varicose
question veins?
strategy Studies will be restricted to English language only.
The review Systematic reviews
strategy RCTs
Non-randomised clinical trials
Analysis We should stratify by the different interventional treatments used in the different studies, as
the difference between use of duplex and no duplex may differ depending on which
treatment is subsequently used (for example, the use of duplex may be important in
optimising surgical outcomes, but may be less important with thermal ablation).
Sub-grouping will occur if there is statistical heterogeneity in meta-analysis results.

Sub-group by disease stage (i.e. CEAP classification C2, C3, C4, C5, C6).
Sub-group by primary and recurrent varicose veins.
1
2

33
Review protocols
1 C.4 Chapter 8 – conservative management

2 C.4.1 Conservative treatment vs. no treatment
3 Table 6: Review protocol: compression vs. no treatment/lifestyle advice

What is the clinical and cost effectiveness of compression therapy compared with no
Review question treatment or lifestyle advice in people with leg varicose veins?
Population Adults with varicose veins in the legs
Intervention Compression therapy, specifically compression hosiery (compression stockings)
Both above knee and below knee compression hosiery will be included.
[There will be no comparison between types of compression therapy].
Comparison • no treatment, or
• non-compressive stockings, or
• placebo, or
• lifestyle advice (including advice on weight loss, exercise, smoking, occupational
standing/leg elevation, etc.)
Outcomes Patient-reported outcome
• Health-related quality of life, using generic (e.g. Medical Outcomes Study Short Form
36, EQ-5D) and disease specific validated tools (e.g. Chronic Venous Insufficiency
• Patient-assessed symptoms (including pain, discomfort, cosmetic concerns/body
image, swelling (oedema), aching, heaviness.)

• Immediate: ≤1 month post intervention
• Intermediate: >1month up to 12 months post intervention
• Long term: >12 months up to 5 years post intervention

• manifestations of reduced arterial flow,
• skin pressure damage
• ulceration,
• allergic reactions,
• blistering, discomfort,
• a sensation of excessive tightness.
• Also non-compliance, and withdrawal from study due to adverse effects

Exclusion Compression therapy applied after an interventional procedure (i.e. after
sclerotherapy).
Compression or bandaging applied for the management of venous ulcers (i.e. C6)
Pneumatic intermittent compression.
Studies that do not specify a varicose veins population

34
Review protocols
What is the clinical and cost effectiveness of compression therapy compared with no
Review question treatment or lifestyle advice in people with leg varicose veins?
Search strategy The databases to be searched are Medline, Embase, The Cochrane Library, CINAHL.
Studies will be restricted to English language only

Search terms Elastic stockings
(graduated) Compression therapy/hosiery/stockings
The review Systematic reviews
strategy RCTs (cross over trials will be included where the time of treatment was short enough
not to result in a natural change in patient condition and the washout period long
enough to negate any impact of the stockings).
If no RCTs, then conference abstracts, and then observational studies.
Analysis Stratification for studies focussed on pregnant women.
A meta-analysis will be conducted on RCTs with appropriate outcome data.
Sub-grouping will occur if there is statistical heterogeneity in meta-analysis results:

Sub-group for disease stage (i.e. CEAP classification, C2, C3, C4, C5).
Sub group for above and below knee hosiery
1

35
Review protocols
1 C.4.2 Compression vs. interventional treatment
2 Table 7: Review protocol: compression vs. interventional treatment

What is the clinical and cost effectiveness of compression therapy compared with
a) stripping surgery; or
b) endothermal ablation; or
Review c) foam sclerotherapy
question in people with leg varicose veins?
Population Adults with varicose veins in the legs
Intervention Compression therapy, specifically compression hosiery (compression stockings)
Both above knee and below knee compression hosiery will be included.
[There will be no comparison between types of compression therapy].
Comparison Foam sclerotherapy ± crossectomy
OR
Stripping surgery + ligation [± phlebectomy]
OR
Endothermal ablation [± foam sclerotherapy/phlebectomy]
Outcomes Patient-reported outcomes
• Patient-assessed symptoms (including pain, discomfort, cosmetic concerns/body image,

• Immediate: ≤1 month post intervention
• Intermediate: >1month up to 12 months post intervention
• Long term: >12 months up to 5 years post intervention

• manifestations of reduced arterial flow,
• major vascular injury,
• skin pressure damage,
• ulceration,
• allergic reactions,
• blistering,
• discomfort,
• sensation of excessive tightness.
• venous thromboembolism (pulmonary embolism [PE] and deep vein thrombosis (DVT);
• Central neurological event (permanent (i.e. stroke, TIA) and transient i.e. migraine,
transient visual disturbance);
• local neurological events (permanent and transient) i.e. nerve injury/damage,
paraesthesia, neuralgia, numbness;
• phlebitis;

36
Review protocols
What is the clinical and cost effectiveness of compression therapy compared with
a) stripping surgery; or
b) endothermal ablation; or
Review c) foam sclerotherapy
question in people with leg varicose veins?
• Also non-compliance, and withdrawal from study due to adverse effects)

Return to work and/or normal activities

Exclusion Studies that do not specify a varicose veins population
Compression therapy applied after an interventional procedure (i.e. after sclerotherapy).
Compression or bandaging applied for the management of venous ulcers (i.e. C6)
Pneumatic intermittent compression.
Cryostripping
strategy Studies will be restricted to English language only
The review RCTs first. If no RCTs, then conference abstracts, and then observational studies.
strategy Systematic reviews
Analysis A meta-analysis will be conducted on RCTs with appropriate outcome data.
Stratification for studies focussed on pregnant women.
Sub-grouping will occur if there is statistical heterogeneity in meta-analysis results:

Sub-group for disease stage (i.e. CEAP classification, C2, C3, C4, C5).
Sub group for above and below knee hosiery
1
2

37
Review protocols
1 C.5 Chapter 9 – interventional treatment

2 C.5.1 Stripping surgery vs. foam sclerotherapy
3 Table 8: Review protocol: Stripping surgery vs. foam sclerotherapy

Review What is the clinical and cost effectiveness of stripping surgery compared with foam
question sclerotherapy in people with truncal leg varicose veins?
Population Adults with truncal leg varicose veins.
Intervention Stripping surgery (including conventional stripping, invagination stripping=inverting
stripping=PIN [perforation invagination], ‘high-tie’=crossectomy, saphenofemoral junction
disconnection, saphenopopliteal) with ligation, sequential stripping surgery.
[± phlebectomy]
[NOTE: Stripping surgery comes hand-in-hand with ligation, i.e. it is normal practice for
ligation to occur before stripping]
Comparison Foam sclerotherapy
[± crossectomy (ligation)]
[NOTE: compression therapy is applied after the procedure as part of the treatment]
language, swelling (oedema), aching, heaviness.
Presence of reflux:
• Within 3 months
• >3–12 months
• >1–5 years


• venous thrombo-embolism [VTE], i.e. pulmonary embolism [PE] and deep vein
thrombosis (DVT);
• phlebitis;


38
Review protocols

The review RCTs first. If no RCTs are available, then consider conference abstracts, and if none are
strategy available then consider observational studies.
Systematic reviews
Stratification from the outset:

• foam sclerotherapy ± crossectomy (i.e. ligation).
• primary and recurrent varicose veins
Further sub-grouping will occur if there is statistical heterogeneity in meta-analysis results.

Key papers Murad MH, Coto-Yglesias F, Zumaeta-Garcia M, Elamin MB, Duggirala MK, Erwin PJ,
Montori VM, and Gloviczki P. A systematic review and meta-analysis of the treatments of
varicose veins. [Review]. Journal of Vascular Surgery 2011; 53: 49S - 65S
Rigby KA, Palfreyman SJ, Beverley C, Michaels JA. Surgery versus sclerotherapy for the
treatment of varicose veins. Cochrane Database Syst Rev. 2004;18;(4):CD004980.
1 C.5.2 Stripping surgery vs. endothermal ablation
2 Table 9: Review protocol: stripping surgery vs. endothermal ablation

Review What is the clinical and cost effectiveness of stripping surgery compared with
question endothermal ablation in people with truncal leg varicose veins?
Intervention Stripping surgery (including conventional stripping, invagination stripping=inverting
disconnection, saphenopopliteal) with ligation, sequential stripping surgery.
[± phlebectomy]
[NOTE: Stripping surgery comes hand-in-hand with ligation, i.e. it is normal practice for
ligation to occur before stripping]
Comparison Endothermal ablation, including:
• radiofrequency ablation
• (endovenous) laser ablation (EVLA)
• steam ablation
[± foam sclerotherapy/phlebectomy (for tributaries)]
language, swelling (oedema), aching, heaviness.
Presence of reflux:

39
Review protocols
Review What is the clinical and cost effectiveness of stripping surgery compared with
• Within 3 months
• >3–12 months
• >1–5 years


thrombosis (DVT);
• phlebitis;


Systematic reviews


Sub-group by types of endothermal ablation
Key papers van den Bos R, Arends L, Kockaert M, Neumann M, and Nijsten T. Endovenous therapies of
lower extremity varicosities: a meta-analysis. [Review] [42 refs]. Journal of Vascular Surgery
2009; 49: 230 - 239

40
Review protocols
1 C.5.3 Foam sclerotherapy vs. endothermal ablations
2 Table 10: Review protocol: foam sclerotherapy versus endothermal ablation

Review What is the clinical and cost effectiveness of foam sclerotherapy compared with
Intervention Foam sclerotherapy(including ultrasound-guided foam sclerotherapy (UGFS))
[± crossectomy (ligation)]
Comparison Endothermal ablation, including:
• (endovenous) laser ablation (EVLA)
• steam ablation
[foam sclerotherapy/phlebectomy (for tributaries)]
Presence of reflux:
• Within 3 months
• >3–12 months
• >1–5 years


• venous thrombo-embolism [VTE], i.e. pulmonary embolism [PE] and deep vein thrombosis
(DVT);
• phlebitis;


41
Review protocols
Review What is the clinical and cost effectiveness of foam sclerotherapy compared with
Search The databases to be searched are Medline, Embase, The Cochrane Library, CINAHL.e
The review RCTs first. If no RCTs are available, then consider conference abstracts of RCTs, and if none
strategy are available then consider observational studies.
Systematic reviews


Sub-group by types of endothermal ablation.
1 C.5.4 Tributary treatment: avulsion surgery vs. foam sclerotherapy
2 Table 11: Review protocol: avulsion surgery vs. foam sclerotherapy for tributary treatment
Review What is the clinical and cost effectiveness of avulsion surgery compared with foam
question sclerotherapy in people with tributary leg varicose veins?
Population Adults with tributary leg varicose veins.
Intervention Avulsion surgery (ambulatory phlebectomy, phlebectomy)
Comparison Foam sclerotherapy to tributary veins. (including ultrasound-guided foam sclerotherapy
(UGFS))
Presence of reflux:
• Within 3 months
• >3–12 months
• >1–5 years


42
Review protocols
Review What is the clinical and cost effectiveness of avulsion surgery compared with foam
question sclerotherapy in people with tributary leg varicose veins?

thrombosis (DVT);
• phlebitis;


Systematic reviews
Within the above sub-groups, further sub-grouping will occur if there is statistical
heterogeneity in meta-analysis results.
1 C.5.5 Truncal treatment and tributary treatment vs. truncal treatment alone
2 Table 12: Review protocol: Truncal treatment and tributary treatment vs. truncal treatment alone
What is the clinical and cost effectiveness of truncal treatment accompanied by tributary
Review treatment (avulsion or sclerotherapy) compared with truncal treatment alone in people
question with leg varicose veins?
1 2 3
Intervention Stripping surgery accompanied by tributary treatments (avulsion / foam sclerotherapy )
OR
4 2
Endothermal ablation accompanied by tributary treatments (avulsion / foam
3
sclerotherapy )
OR
3 2
Foam sclerotherapy accompanied by tributary treatments (avulsion / foam
3
sclerotherapy )
1: Stripping surgery (including conventional stripping, invagination stripping=inverting

stripping=PIN [perforation invagination], ‘high-tie’=crossectomy, sapheno-femoral
junction disconnection, sapheno-popliteal) with ligation, sequential stripping surgery.[±
phlebectomy]
2: Avulsion surgery (ambulatory phlebectomy, phlebectomy)

43
Review protocols
3: Foam sclerotherapy
4: Endothermal ablation, including:
radiofrequency ablation
(endovenous) laser ablation (EVLA, EVLT)
steam ablation
Comparison The comparator in each case will be the truncal intervention, but without tributary
treatment (avulsion / sclerotherapy) as an adjunct
Outcomes Patient-reported outcomes:-
• Patient-assessed symptoms (including pain, discomfort, cosmetic concerns/cosmesis*,
Presence of reflux:
• Within 3 months
• >3–12 months
• >1–5 years

Adverse events from intervention, including:

• venous thromboembolism (pulmonary embolism [PE] and deep vein thrombosis (DVT –
to be reported separately)
• global neurological event (i.e. stroke, TIA);
• local neurological events (i.e. nerve injury/damage, paresthesia, neuralgia, numbness).
• post-procedure pain
• phlebitis

Return to work / normal activities


44
Review protocols
Systematic reviews

2 C.6 Chapter 10 – compression after treatment

3 Table 13: Review protocol: compression after interventional treatment vs. interventional
4 treatment alone
What is the clinical and cost effectiveness of interventional treatment followed by
compression compared with interventional treatment alone in people with leg varicose
Review veins, and, if so, what type of compression, pressure of compression and/or duration of
question compression is optimal?
1 2
Intervention Stripping surgery followed by compression
OR
3 2
Avulsion surgery followed by compression
OR
4 2
Endothermal ablation followed by compression
OR
5 2
Foam sclerotherapy followed by compression
1: Stripping surgery (including conventional stripping, invagination stripping=inverting

disconnection, saphenopopliteal) with ligation, sequential stripping surgery.[± phlebectomy].
Note: Short-term (up to 7 days) ‘routine’ elastic bandaging is allowed in both groups.
2: Compression therapy, specifically compression hosiery (compression stockings). Both

above knee and below knee compression hosiery will be included.
3: Avulsion surgery (ambulatory phlebectomy, phlebectomy)

4: Endothermal ablation, including:

• (endovenous) laser ablation (EVLA, EVLT)
• steam ablation

45
Review protocols

5: Foam sclerotherapy[ ± crossectomy (ligation)]

Comparison
For the first part of the review question, the comparator in each case will be as the
intervention, but without compression as an adjunct.
For the second part of the review question, the comparator will be as the intervention but
adjunctive compression will vary in terms of:
• another type of compression (i.e. bandaging)
• a different compression pressure
• a different duration of treatment
• Patient-assessed symptoms (including pain, discomfort, cosmetic concerns/cosmesis*,
Presence of reflux:
• Within 3 months
• >3–12 months
• >1–5 years

Adverse events from intervention, including:

• venous thrombo-embolism (i.e. pulmonary embolism [PE] and deep vein thrombosis (DVT)
– to be reported separately)
• global neurological event (i.e. stroke);
• local neurological events (i.e. nerve injury/damage, paresthesia, neuralgia, numbness).
• post-procedure pain
• phlebitis


46
Review protocols

Return to work / normal activities

Systematic reviews
1
2

47
Review protocols
1 C.7 Economic review protocol

2 Table 14: Appended economic review protocol
Review
question All questions – health economic evidence
Objectives To identify economic studies relevant to the review questions set out above.
Criteria Populations, interventions and comparators as specified in the individual review protocols
above. Must be a relevant economic study design (cost-utility analysis, cost-benefit analysis,
cost-effectiveness analysis, cost-consequence analysis, comparative cost analysis).
Search An economic study search was undertaken using population specific terms and an economic
strategy study filter – see Appendix F
Review Each study is assessed using the NICE economic evaluation checklist – NICE (2009) Guidelines
strategy Manual.
Inclusion/exclusion criteria
If a study is rated as both ‘Directly applicable’ and ‘minor limitations’ (using the NICE economic
evaluation checklist) then it should be included in the guideline. An evidence table should be
completed and it should be included in the economic profile.
If a study is rated as either ‘Not applicable’ or ‘Very serious limitations’ then it should be
excluded from the guideline. It should not be included in the economic profile and there is no
need to include an evidence table.
If a study is rated as ‘Partially applicable’ and/or ‘potentially serious limitations’ then there is
discretion over whether it should be included. The health economist should make a decision
based on the relative applicability and quality of the available evidence for that question, in
discussion with the GDG if required. The ultimate aim being to include studies that are helpful
for decision making in the context of the guideline and current NHS setting. Where exclusions
occur on this basis, this should be noted in the relevant section of the guideline with
references.
Also exclude:
• unpublished reports unless submitted as part of a call for evidence
• abstract-only studies
• letters
• editorials
a
• reviews of economic evaluations
• foreign language articles
Where there is discretion

The health economist should be guided by the following hierarchies:
Setting:
1. UK NHS
2. OECD countries with predominantly public health insurance systems (e.g. France,
Germany, Sweden)
3. OECD countries with predominantly private health insurance systems (e.g. USA,
Switzerland)
4. Non-OECD settings (always ‘Not applicable’)
Economic study type:

48
Review protocols
Review
question All questions – health economic evidence
1. Cost-utility analysis
2. Other type of full economic evaluation (cost-benefit analysis, cost-effectiveness
analysis, cost-consequence analysis)
3. Comparative cost analysis
4. Non-comparative cost analyses including cost of illness studies (always ‘Not
applicable’)
Year of analysis:
• The more recent the study, the more applicable it is
Quality and relevance of effectiveness data used in the economic analysis:

• The more closely the effectiveness data used in the economic analysis matches with the
studies included for the clinical review the more useful the analysis will be to decision
making for the guideline.
1 (a) Recent reviews will be ordered although not reviewed. The bibliographies will be checked for relevant studies, which will
2 then be ordered.

49
Clinical article selection
1 Appendix D: Clinical article selection

2 D.1 Chapter 5 – patient perceptions and expectations
3 Figure 1: Clinical article selection: patient perceptions and expectations
Titles and
abstracts
identified, n = 69
Full copies Excluded, n = 55

retrieved and Not relevant
assessed for design,
eligibility, n = 14 intervention,
comparison and
specified
outcomes
Publications Excluded, n = 7
included in review, (see exclusion list)
n=7
5
6

50
1 D.2 Chapter 6 – referral to a vascular service

2 D.2.1 Risk factors associated with disease progression
Figure 2: Clinical article selection: factors associated with disease progression
3
4

51
1 D.2.2 Risk factors affecting treatment success
2 Figure 3: Clinical article selection: factors associated with treatment success/failure
Titles and
abstracts
identified, n = 681

retrieved and Non- relevant
comparison and
specified
outcomes
n=7
3
4
5

52
1 D.3 Chapter 7 – assessment for treatment

2 D.3.1 Diagnostic accuracy of hand held Doppler
3 Figure 4: Clinical article selection: diagnostic accuracy of hand held Doppler
Titles and
abstracts
identified, n = 160

comparison and
specified
outcomes
n = 12
4
5

53
1 D.3.2 Assessment with duplex prior to interventional treatment
Figure 5: Clinical article selection: assessment with duplex prior to interventional treatment

54
1 D.4 Chapter 8 – conservative management

2 D.4.1 Compression vs. no treatment
3 Figure 6: Clinical article selection: compression vs. no treatment
Titles and
abstracts
identified, n = 786

comparison and
specified
outcomes
n=8
4
5

55
1 D.4.2 Compression vs. interventional treatment
2 Figure 7: Clinical article selection for compression vs. interventional treatment
Titles and abstracts

identified, n = 943
Full copies Excluded, n=934

retrieved and
assessed for
eligibility, n = 11
included in review,
n=2
3
4 D.5 Chapter 9 – interventional treatment

5 D.5.1 Stripping surgery vs. foam sclerotherapy
6 Figure 8: Clinical article selection: Stripping surgery vs. foam sclerotherapy review

identified, n = 279

retrieved and
assessed for
eligibility, n = 27
included in review,
n=8
7

56
2 D.5.2 Stripping surgery vs. endothermal ablation
3 Figure 9: Clinical article selection: stripping surgery vs. endothermal ablation

identified, n =279

retrieved and
assessed for
eligibility, n = 36
included in review,
n = 16
4
5 D.5.3 Foam sclerotherapy vs. endothermal ablation
6 Figure 10: Clinical article selection for foam sclerotherapy vs. endothermal ablation review

identified, n = 143

retrieved and
assessed for
eligibility, n = 6
included in review,
n = 3 (2 RCTs and
one observational
study
7

57
1 D.5.4 Tributary treatment: avulsion vs. foam sclerotherapy
2 Figure 11: Clinical article selection: foam sclerotherapy vs. avulsion for tributary veins

identified, n = 186

retrieved and
assessed for
eligibility, n = 5
included in review,
n=0
3

58
1 D.5.5 Truncal treatment and tributary treatment vs. truncal treatment alone
Figure 12: Clinical article selection: truncal with tributary treatment vs. truncal treatment alone
Titles and
abstracts
identified, n = 508
(the avulsion and
sclerotherapy
searches (RCT plus
observational)

comparison and
specified
outcomes
n=1

59
1 D.6 Chapter 10 – compression after interventional treatment

Figure 13: Clinical article selection: Interventional treatment with compression vs. interventional
treatment alone

identified, n = 785

retrieved and
assessed for
eligibility, n = 21
n=2

60
Economic article selection
1 Appendix E: Economic article selection

2 E.1 Chapter 5 – patient perceptions and expectations
Figure 14: Economic article selection: patient perceptions and expectations

identified (whole
guideline), n = 332
Full copies retrieved Excluded*,

and assessed for n = 305
eligibility (whole
guideline), n = 27
Potentially Excluded*,
includable n = 27
publications (this
review only), n = 0
Publications Excluded, n = 0 * Non-relevant population, intervention,

included in review, comparison, design or setting; non-
n=0 (see exclusion list) English language
3
4

61
2 E.2 Chapter 6 – referral to a vascular service

Figure 15: Economic article selection: referral to a vascular service

identified (whole
guideline), n = 332

eligibility (whole
guideline), n = 27
includable n = 27
publications (this
review only), n = 0

3
4

62
1 E.3 Chapter 7 – assessment for treatment

2 E.3.1 Duplex vs. Hand Held Doppler
3 Figure 16: Economic article selection: duplex vs. hand held doppler review

identified (whole
guideline), n = 332

eligibility (whole
guideline), n = 27
includable n = 27
publications (this
review only), n = 0

5

63
1 E.3.2 Duplex assessment prior to interventional treatment
Figure 17: Economic article selection: duplex assessment prior to interventional treatment

identified (whole
guideline), n = 332

eligibility (whole
guideline), n = 27
includable n = 26
publications (this
review only), n = 1


64
1 E.4 Chapter 8 – conservative management

2 E.4.1 Compression vs. no treatment
Figure 18: Economic article selection: compression vs.no treatment

identified (whole
guideline), n = 332

eligibility (whole
guideline), n = 27
includable n = 27
publications (this
review only), n = 0


65
1 E.4.2 Compression vs. interventional treatment
Figure 19: Economic article selection: compression vs. interventional treatment

identified (whole
guideline), n = 332

eligibility (whole
guideline), n = 27
includable n = 23
publications (this
review only), n = 4


66
1 E.5 Chapter 9 – interventional treatment

2 E.5.1 Stripping surgery vs. foam sclerotherapy
Figure 20: Economic article selection: stripping surgery vs. foam sclerotherapy

identified (whole
guideline), n = 332

eligibility (whole
guideline), n = 27
includable n = 21
publications (this
review only), n = 6

3
4

67
1 E.5.2 Stripping surgery vs. endothermal ablation
Figure 21: Economic article selection: stripping surgery vs. endothermal ablation

identified (whole
guideline), n = 332

eligibility (whole
guideline), n = 27
includable n = 16
publications (this
review only), n = 11


68
1 E.5.3 Foam sclerotherapy vs. endothermal ablation
Figure 22: Economic article selection: foam sclerotherapy vs. endothermal ablation

identified (whole
guideline), n = 332

eligibility (whole
guideline), n = 27
includable n = 15
publications (this
review only), n = 2

2
3

69
1 E.5.4 Tributary treatment: avulsion vs. foam sclerotherapy
2 Figure 23: Economic article selection: avulsion vs. foam sclerotherapy

identified (whole
guideline), n = 332

eligibility (whole
guideline), n = 27
includable n = 27
publications (this
review only), n = 0

4
5
6

70
1 E.5.5 Truncal treatment and tributary treatment vs. truncal treatment alone
2 Figure 24: Economic article selection: truncal treatment and tributary treatment vs. truncal
3 treatment alone

identified (whole
guideline), n = 332

eligibility (whole
guideline), n = 27
includable n = 26
publications (this
review only), n = 1

5
6
7

71
1 E.6 Chapter 10 – compression after treatment

2 Figure 25: Economic article selection: compression after treatment

identified (whole
guideline), n = 332

eligibility (whole
guideline), n = 27
includable n = 27
publications (this
review only), n = 0

3
4

72
Literature search strategies
1 Appendix F: Literature search strategies

2 Contents
3
Introduction Search methodology
Section F.1 Study filter terms
F.1.1 Systematic reviews (SR)
F.1.2 Randomized controlled trials (RCT)
F.1.3 Observational studies
F.1.4 Economic studies
F.1.5 Quality of life studies
F.1.6 Diagnostic accuracy
Section F.2 Standard population search strategy
Populations used for all search questions unless stated in F.3
Section F.3 Searches for specific questions with intervention (and population where different from
F.2)
F.3.1 Patient information
F.3.2 Assessment for referral
F.3.3 Assessment for treatment
F.3.4 Conservative management
F.3.5 Interventional treatment
F.3.6 Compression post treatment
Section F.4 Economic searches
F.4.1 Economic reviews
F.4.2 Quality of life reviews
4 Introduction
5 Search strategies used for the Varicose Veins guideline were run in accordance with the Guidelines
6 Manual (NICE, 2009). All searches were run finally on 17 October 2012 unless otherwise stated. Any
7 studies added to the databases after this date were not included unless specifically stated in the text.
8 Clinical searches
9 Searches for clinical reviews were run in Medline (OVID), Embase (OVID), and the Cochrane Library
10 (Wiley). Typically, searches were constructed in the following way:
11
12 A PICO format was used for intervention searches. Population (P) terms were combined with
13 Intervention (I) and sometimes Comparison (C) terms (as indicated in the tables under each
14 individual question in Section F.3). An intervention can be a drug, a procedure or a diagnostic
15 test. Outcome (O) terms are rarely used in search strategies for interventions. Study type
16 filters (F.1) were added where appropriate.
17 In addition to the databases outlined above, searches F.3.1 and F.3.4 were run in Cinahl (EBSCO), and
18 F.3.1 in PsycINFO (OVID).
19

73
1 Economic searches
2 Searches for economic evidence were run in Medline (Ovid), Embase (Ovid), the NHS Economic
3 Evaluations Database (NHS EED), the Health Technology Assessment (HTA) database and the Health
4 Economic Evaluation Database (HEED). NHS EED and HTA were searched via the Cochrane (Wiley)
5 interface. For Medline and Embase an economic filter (see F.1.4) was applied to the standard
6 population. All other searches were conducted using only population terms.
7 F.1 Study design search terms

8 F.1.1 Systematic review (SR) search terms
9 Medline search terms
1. Meta-analysis/
2. Meta-analysis as topic/
3. (meta analy* or metanaly* or metaanaly*).ti,ab.
4. ((systematic* or evidence*) adj2 (review* or overview*)).ti,ab.
5. (reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.
6. (search strategy or search criteria or systematic search or study selection or data
extraction).ab.
7. (search* adj4 literature).ab.
8. (medline or pubmed or cochrane or embase or psychlit or psyclit or psychinfo or psycinfo or
cinahl or science citation index or bids or cancerlit).ab.
9. cochrane.jw.
10. or/1-9
10 Embase search terms

1. Systematic review/
2. Meta-analysis/
3. (meta analy* or metanaly* or metaanaly*).ti,ab.
4. ((systematic or evidence) adj2 (review* or overview*)).ti,ab.
5. (reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.
6. (search strategy or search criteria or systematic search or study selection or data
extraction).ab.
7. (search* adj4 literature).ab.
8. (medline or pubmed or cochrane or embase or psychlit or psyclit or psychinfo or psycinfo or
cinahl or science citation index or bids or cancerlit).ab.
9. ((pool* or combined) adj2 (data or trials or studies or results)).ab.
10. cochrane.jw.
11. or/1-10
11 F.1.2 Randomised controlled studies (RCTs) search terms

1. Randomized controlled trial.pt.
2. Controlled clinical trial.pt.
3. randomi#ed.ab.
4. placebo.ab.
5. randomly.ab.

74
6. Clinical trials as topic.sh.

7. trial*.ti.
8. or/1-7

1. random*.ti,ab.
2. factorial*.ti,ab.
3. (crossover* or cross over*).ti,ab.
4. ((doubl* or singl*) adj blind*).ti,ab.
5. (assign* or allocat* or volunteer* or placebo*).ti,ab.
6. Crossover procedure/
7. Single blind procedure/
8. Randomized controlled trial/
9. Rouble blind procedure/
10. or/1-9
2 F.1.3 Observational studies search terms

1. Epidemiologic studies/
2. exp Case control studies/
3. exp Cohort studies/
4. Cross-sectional studies/
5. case control.ti,ab.
6. (cohort adj (study or studies or analys*)).ti,ab.
7. ((follow-up or observational or uncontrolled or non randomi#ed or nonrandomi#ed or
epidemiologic*) adj (study or studies)).ti,ab.
8. ((longitudinal or retrospective or prospective or cross sectional) and (study or studies or
review or analys* or cohort*)).ti,ab.
9. or/1-8

1. Clinical study/
2. exp Case control study/
3. Family study/
4. Longitudinal study/
5. Retrospective study/
6. Prospective study/
7. Cross-sectional study/
8. Cohort analysis/
9. Follow-up/
10. cohort*.ti,ab.
11. 9 and 10
13. (cohort adj (study or studies or analys*)).ti,ab.

75

16. or/1-8,11-15
1 F.1.4 Health economic search terms

1. Economics/
2. Value of life/
3. exp "Costs and cost analysis"/
4. exp Economics, Hospital/
5. exp Economics, Medical/
6. exp Resource allocation/
7. Economics, Nursing/
8. Economics, Pharmaceutical/
9. exp "Fees and charges"/
10. exp Budgets/
11. budget*.ti,ab.
12. cost*.ti,ab.
13. (economic* or pharmaco?economic*).ti,ab.
14. (price* or pricing*).ti,ab.
15. (financ* or fee or fees or expenditure* or saving*).ti,ab.
16. (value adj2 (money or monetary)).ti,ab.
17. resourc* allocat*.ti,ab.
18. (fund or funds or funding* or funded).ti,ab.
19. (ration or rations or rationing* or rationed).ti,ab.
20. ec.fs.
21. or/1-20

1. Health economics/
2. exp Economic evaluation/
3. exp Health care cost/
4. exp Fee/
5. Budget/
6. Funding/
7. Resource allocation/
8. budget*.ti,ab.
9. cost*.ti,ab.
10. (economic* or pharmaco?economic*).ti,ab.
11. (price* or pricing*).ti,ab.
12. (financ* or fee or fees or expenditure* or saving*).ti,ab.
13. (value adj2 (money or monetary)).ti,ab.
14. resourc* allocat*.ti,ab.
15. (fund or funds or funding* or funded).ti,ab.
16. (ration or rations or rationing* or rationed).ti,ab.

76
1 F.1.5 Quality of life search terms

1. Quality-adjusted life years/
2. Sickness impact profile/
3. (quality adj2 (wellbeing or well being)).ti,ab.
4. sickness impact profile.ti,ab.
5. disability adjusted life.ti,ab.
6. (qal* or qtime* or qwb* or daly*).ti,ab.
7. (euroqol* or eq5d* or eq 5d*).ti,ab.
8. (qol* or hql* or hqol* or h qol* or hrqol* or hr qol*).ti,ab.
9. (health utility* or utility score* or disutilit*).ti,ab.
10. (hui or hui1 or hui2 or hui3).ti,ab.
11. health* year* equivalent*.ti,ab.
12. (hye or hyes).ti,ab.
13. rosser.ti,ab.
14. (willingness to pay or time tradeoff or time trade off or tto or standard gamble*).ti,ab.
15. (sf36 or sf 36 or short form 36 or shortform 36 or shortform36).ti,ab.
20. or/1-19

1. Quality adjusted life year/
2. "Quality of life index"/
3. Short form 12/ or Short form 20/ or Short form 36/ or Short form 8/
4. Sickness impact profile/
5. (quality adj2 (wellbeing or well being)).ti,ab.
6. sickness impact profile.ti,ab.
7. disability adjusted life.ti,ab.
8. (qal* or qtime* or qwb* or daly*).ti,ab.
9. (euroqol* or eq5d* or eq 5d*).ti,ab.
10. (qol* or hql* or hqol* or h qol* or hrqol* or hr qol*).ti,ab.
11. (health utility* or utility score* or disutilit*).ti,ab.
12. (hui or hui1 or hui2 or hui3).ti,ab.
13. health* year* equivalent*.ti,ab.
14. (hye or hyes).ti,ab.
15. rosser.ti,ab.
16. (willingness to pay or time tradeoff or time trade off or tto or standard gamble*).ti,ab.

77
22. or/1-21
1 F.1.6 Diagnostic accuracy

1. exp "Sensitivity and specificity"/
2. (sensitivity or specificity).ti,ab.
3. ((pre test or pretest or post test) adj probability).ti,ab.
4. (prognos* or predict*).ti,ab,hw.
5. (PPV or NPV).ti,ab.
6. Likelihood function/
7. (ROC curve* or AUC).ti,ab.
8. (diagnos* adj2 (performance* or accurac* or utilit* or value* or efficien* or
effectiveness)).ti,ab.
9. gold standard.ab.
10. (improve* adj3 (outcome* or result*)).ti,ab.
11. Treatment outcome/
12. or/1-11

1. exp "Sensitivity and specificity"/
2. Diagnostic accuracy/
3. Diagnostic test accuracy study/
5. (prognos* or predict*).ti,ab,hw.
6. (sensitivity or specificity).ti,ab.
7. ((pre test or pretest or post test) adj probability).ti,ab.
8. (PPV or NPV).ti,ab.
9. likelihood ratio*.ti,ab.
10. (ROC curve* or AUC).ti,ab.
11. (diagnos* adj2 (performance* or accurac* or utilit* or value* or efficien* or
effectiveness)).ti,ab.
12. (improve* adj3 (outcome* or result*)).ti,ab.
13. gold standard.ab.
14. or/1-13
4 F.2 Standard population search strategy

1. exp Varicose veins/
2. (varicos* adj5 vein*).ti,ab.
3. Saphenous vein/
4. (sapheno* adj3 (vein* or junction* or incompet* or reflux or insufficien*)).ti,ab.
5. exp Coronary artery bypass/
6. ((coronary or bypass) and graft).ti,ab.
7. (3 or 4) not (5 or 6)
8. 1 or 2 or 7

78
9. Venous insufficiency/
10. ((venous or vein* or varico* or truncal or valvular) adj3 (insufficien* or incompet* or disorder*
or reflux)).ti,ab.
11. ((venous or varico*) adj disease*).ti,ab.
12. ((perforator or superficial or tortuous) adj3 vein*).ti,ab.
13. (varix or varices or varicosi* or ceap).ti,ab.
14. ((varico* or venous or vein*) adj3 ulcer*).ti,ab.
15. or/9-14
16. exp Lower extremity/
17. (lower adj2 extremit*).ti,ab.
18. (leg* or limb* or calf or calves or thigh* or groin* or ankle* or foot or feet or pelvis or pelvic or
vulva* or vulvo* or ovari* or ovary or vagina* or uterus or uterin*).ti,ab.
19. or/16-18
20. 8 or (15 and 19)
21. limit 20 to english language
22. Letter/
23. Editorial/
24. News/
25. exp Historical article/
26. Anecdotes as topic/
27. Comment/
28. Case report/
29. (letter or comment*).ti.
30. or/22-29
31. 30 not (Randomized controlled trial/ or random*.ti,ab.)
32. Animals/ not Humans/
33. exp Animals, Laboratory/
34. exp Animal experimentation/
35. exp Models, Animal/
36. exp Rodentia/
37. (rat or rats or mouse or mice).ti.
38. or/31-37
39. 21 not 38

1. Varicosis/
2. Leg varicosis/
4. Saphenous vein/
5. (sapheno* adj3 (vein* or junction or incompet* or reflux or insufficien*)).ti,ab.
6. exp Coronary artery bypass graft/
7. ((coronary or bypass) and graft).ti,ab.
8. (4 or 5) not (6 or 7)
9. 1 or 2 or 3 or 8
10. exp Vein insufficiency/

79
or reflux)).ti,ab.
16. or/10-15
17. exp Leg/
18. (lower adj2 extremit*).ti,ab.
19. (leg* or limb* or calf or calves or thigh* or groin* or ankle* or foot or feet or pelvis or pelvic or
vulva* or vulvo* or ovari* or ovary or vagina* or uterus or uterin*).ti,ab.
20. or/17-19
21. 9 or (16 and 20)
22. limit 21 to english language
23. Letter.pt. or Letter/
24. Note.pt.
25. Editorial.pt.
26. Case report/ or Case study/
27. (letter or comment*).ti.
28. or/23-27
29. 28 not (randomized controlled trial/ or random*.ti,ab.)
30. Animal/ not Human/
31. Nonhuman/
32. exp Animal experiment/
33. exp Experimental animal/
34. Animal model/
35. exp Rodent/
36. (rat or rats or mouse or mice).ti.
37. or/29-36
38. 22 not 37
1 Cinahl search terms

S1 (MH "Varicose Veins")
S2 varicos* n5 vein*
S3 (MH "Saphenous Vein")
S4 sapheno* and (vein* or junction* or incompet* or reflux or insufficien*)
S5 (MH "Coronary Artery Bypass+")
S6 (S3 or S4) not S5
S7 S1 or S2 or S6
S8 (MH "Venous Insufficiency")
S9 (venous or vein* or varico* or truncal or valvular) and (insufficien* or incompet* or disorder*
or reflux)
S10 (perforator n3 vein*) or (superficial n3 vein*) or (tortuous n3 vein*)
S11 varix or varices or varicosi* or ceap
S12 (venous n1 disease*) or (varico* n1 disease*)
S13 (varico* n3 ulcer*) or (vein* n3 ulcer*) or (venous n3 ulcer*)
S14 S8 or S9 or S10 or S11 or S12 or S13

80
S15 (MH "Lower Extremity+")

S16 lower n2 extremit*
S17 leg* or limb* or calf or calves or thigh* or groin* or ankle* or foot or feet or pelvis or pelvic or
vulva* or vulvo* or ovari* or ovary or vagina* or uterus or uterin*
S18 S15 or S16 or S17
S19 S7 or (S14 and S18)
1 Cochrane search terms

#1 MeSH descriptor Varicose Veins explode all trees
#2 (varicos* NEAR/5 vein*):ti,ab
#3 MeSH descriptor Saphenous Vein, this term only
#4 (sapheno* NEAR/3 (vein* or junction* or incompet* or reflux or insufficien*)):ti,ab
#5 MeSH descriptor Coronary Artery Bypass explode all trees
#6 ((coronary or bypass) and graft):ti,ab
#7 (( #3 or #4 ) and not ( #5 OR #6 ))
#8 (#1 or #2 or #7)
#9 MeSH descriptor Venous Insufficiency, this term only
#10 ((venous or vein* or varico* or truncal or valvular) NEAR/3 (insufficien* or incompet* or
disorder* or reflux)):ti,ab
#11 ((perforator or superficial or tortuous) NEAR/3 vein*):ti,ab
#12 (varix or varices or varicosi* or ceap):ti,ab
#13 ((varico* or vein* or venous) NEAR/3 ulcer*):ti,ab
#14 ((venous or varico*) NEXT disease*):ti,ab
#15 (#9 or #10 or #11 or #12 or #13 or #14)
#16 MeSH descriptor Lower Extremity explode all trees
#17 (lower NEAR/2 extremit*):ti,ab
#18 (leg* or limb* or calf or calves or thigh* or groin* or ankle* or foot or feet or pelvis or pelvic or
vulva* or vulvo* or ovari* or ovary or vagina* or uterus or uterin*):ti,ab
#19 (#16 or #17 or #18)
#20 (#8 or ( #15 and #19 ))
2 F.3 Searches by specific questions

3 F.3.1 Patient information
4 Q. What are the perceptions and expectations of people with varicose veins (e.g. natural
5 history, treatment) and how can they be addressed?
6 Search constructed by combining the columns in the following table using the AND Boolean operator
Population Intervention Study filter used Date parameters
Varicose veins Patient information None All years - 17/10/2012

1. ((client* or patient* or user* or carer* or consumer* or customer* or health) adj3
(information* or educat* or knowledge or literacy or belief* or perception* or understanding
or expectation* or prefer* or satisfaction or acceptance or compliance or adherence or
concordance)).ti,ab,hw.
2. (information* adj3 (need* or requirement* or support* or seek* or access* or
disseminat*)).ti,ab,hw.

81
3. ((patient* or user* or carer* or consumer* or customer* or health) adj3 (literature or leaflet*

or booklet* or pamphlet* or questionnaire* or survey* or handout* or internet or website* or
consult* or interview*)).ti,ab.
4. Telemedicine/
5. Interview/
6. Telephone/
7. Publications/
8. Pamphlets/
9. Internet/
10. or/1-9

1. ((client* or patient* or user* or carer* or consumer* or customer* or health or medical) adj3
(information* or educat* or knowledge or literacy or belief* or perception* or understanding
or expectation* or attitude* or prefer* or satisfaction or acceptance or compliance or
adherence or concordance or advocacy)).ti,ab,hw.
2. (information* adj3 (need* or requirement* or support* or seek* or access* or
disseminat*)).ti,ab,hw.
3. ((patient* or user* or carer* or consumer* or customer* or health) adj3 (literature or leaflet*
or booklet* or pamphlet* or questionnaire* or survey* or handout* or internet or website* or
consult* or interview*)).ti,ab.
4. exp Telehealth/
5. exp Interview/
6. Telephone/
7. Publication/
8. Internet/
9. or/1-8

S1. (MH "Varicose Veins")
S2. varicos* n5 vein*
S3. (MH "Saphenous Vein")
S4. sapheno* and (vein* or junction* or incompet* or reflux or insufficien*)
S5. (MH "Coronary Artery Bypass+")
S6. (S3 or S4) not S5
S7. S1 or S2 or S6
S8. (MH "Venous Insufficiency")
S9. (venous or vein* or varico* or truncal or valvular) and (insufficien* or incompet* or disorder*
or reflux)
S10. (perforator n3 vein*) or (superficial n3 vein*) or (tortuous n3 vein*)
S11. varix or varices or varicosi* or ceap
S12. (venous n1 disease*) or (varico* n1 disease*)
S13. (varico* n3 ulcer*) or (vein* n3 ulcer*) or (venous n3 ulcer*)
S14. S8 or S9 or S10 or S11 or S12 or S13
S15. (MH "Lower Extremity+")
S16. lower n2 extremit*
S17. leg* or limb* or calf or calves or thigh* or groin* or ankle* or foot or feet or pelvis or pelvic or
vulva* or vulvo* or ovari* or ovary or vagina* or uterus or uterin*

82
S18. S15 or S16 or S17

S19. S7 or (S14 and S18)
S20. information* n2 need* or information* n2 requirement* or information* n2 support* or
information* n2 seek* or information* n2 access* or information* n2 disseminat*
S21. patient* n3 information* or patient* n3 knowledge or patient* n3 educat*
S22. carer* n3 information* or carer* n3 knowledge or carer* n3 educat* or health* n3
information* or health* n3 educat*
S23. patient* n3 literature or patient* n3 leaflet* or patient* n3 booklet* or patient* n3 pamphlet*
or patient* n3 questionnaire* or patient* n3 survey* or patient* n3 handout* or patient* n3
internet or patient* n3 website*
S24. TI (patient* or satisfaction*) and (questionnaire* or survey*)
S25. (MH "Access to Information+")
S26. S20 or S21 or S22 or S23 or S24 or S25
S27. S19 and S26
S28. PT anecdote or PT audiovisual or PT bibliography or PT biography or PT book or PT book
review or PT brief item or PT cartoon or PT commentary or PT computer program or PT
editorial or PT games or PT glossary or PT historical material or PT interview or PT letter or PT
listservs or PT masters thesis or PT obituary or PT pamphlet or PT pamphlet chapter or PT
pictorial or PT poetry or PT proceedings or PT “questions and answers” or PT response or PT
software or PT teaching materials or PT website
S29. S27 not S28
S30. English Language OR Exclude Medline records
S31. S29 and S30

#1. MeSH descriptor Patient Acceptance of Health Care, this term only
#2. MeSH descriptor Patient Compliance, this term only
#3. MeSH descriptor Patient Education as Topic, this term only
#4. MeSH descriptor Patient Preference, this term only
#5. MeSH descriptor Patient Satisfaction, this term only
#6. MeSH descriptor Consumer Health Information, this term only
#7. MeSH descriptor Consumer Satisfaction, this term only
#8. MeSH descriptor Health Literacy, this term only
#9. MeSH descriptor Health Knowledge, Attitudes, Practice, this term only
#10. MeSH descriptor Telemedicine, this term only
#11. MeSH descriptor Access to Information, this term only
#12. MeSH descriptor Information Dissemination, this term only
#13. MeSH descriptor Information Seeking Behavior, this term only
#14. MeSH descriptor Pamphlets, this term only
#15. MeSH descriptor Internet, this term only
#16. MeSH descriptor Interviews as Topic explode all trees
#17. MeSH descriptor Telephone, this term only
#18. MeSH descriptor Telemedicine, this term only
#19. ((client* or patient* or user* or carer* or consumer* or customer* or health) NEAR/3
(information* or educat* or knowledge or literacy or belief* or perception* or attitude* or
understanding or expectation* or prefer* or satisfaction or acceptance or compliance or
adherence or concordance)):ti,ab
#20. (information* NEAR/3 (need* or requirement* or support* or seek* or access* or

83
disseminat*)):ti,ab
#21. ((patient* or user* or carer* or consumer* or customer* or health) NEAR/3 (literature or
leaflet* or booklet* or pamphlet* or questionnaire* or survey* or handout* or internet or
website* or consult* or interview*)):ti,ab
#22. (#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or
#16 or #17 or #18 or #19 or #20 or #21)
1 PsycINFO search terms

or reflux)).ti,ab.
7. (leg* or limb* or calf or calves or thigh* or groin* or ankle* or foot or feet or lower
extremit*).ti,ab.
8. (2 or 3 or 4 or 5 or 6) and 7
9. 1 or 8
2 F.3.2 Assessment for referral
3 F.3.2.1 Disease progression
4 Q. a) In people with leg varicose veins at CEAP class C2 which signs, symptoms and/or
5 patient characteristics are associated with disease progression to i) C3, ii) C4* iii) C6?
6
7 b) In people with leg varicose veins at CEAP class C3 which signs, symptoms and/or
8 patient characteristics are associated with disease progression to i) C4* ii) C6?
9
10 c) In people with leg varicose veins at CEAP class C4* which signs, symptoms and/or
11 patient characteristics are associated with disease progression to C6?
Varicose veins Disease classification Observational studies* All years - 17/10/2012
AND disease [Medline and Embase only]
progression
13 *Observational search filter in F.1.3 expanded for this question

1. (CEAP or C2 or C3 or C4 or C5 or C6 or C-2 or C-3 or C-4 or C-5 or C-6).ti,ab.
2. (class* or stage* or staging).ti,ab.
3. (skin adj2 (discol* or change* or pigment*)).ti,ab.
4. (ulcer* or oedem* or edem* or lipoderm* or eczema or atroph*).ti,ab.
5. or/1-4
6. Disease progression/
7. Natural history/
8. Risk factors/
9. (risk* or course* or predict* or incidence or prognos* or progress* or natural history).ti,ab.

84
10. or/6-9
11. 5 and 10
12. Epidemiologic studies/
13. exp Case control studies/
14. exp Cohort studies/
15. Cross-sectional studies/
19. (cohort* or group* or subgroup* or participant*).ti,ab.
20. or/12-19
21. 11 and 20

1. Disease classification/
2. (CEAP or C2 or C3 or C4 or C5 or C6 or C-2 or C-3 or C-4 or C-5 or C-6).ti,ab.
3. (class* or stage* or staging).ti,ab.
4. (skin adj2 (discol* or change* or pigment*)).ti,ab.
5. (ulcer* or oedem* or edem* or lipoderm* or eczema or atroph*).ti,ab.
6. or/1-5
7. Risk factor/
8. Disease course/
9. Disease exacerbation/
10. Predictive value/
11. (risk* or course* or predict* or incidence or prognos* or progress* or natural history).ti,ab.
12. or/7-11
13. 6 and 12
14. Clinical study/
15. exp Case control study/
16. Family study/
17. Longitudinal study/
18. Retrospective study/
19. Prospective study/
20. Cross-sectional study/
21. Cohort analysis/
22. Follow-up/
26. (cohort* or group* or subgroup* or participant*).ti,ab.
27. or/14-26
28. 13 and 27

85
1 F.3.2.2 Prediction of treatment outcomes
2 Q. In people with leg varicose veins are there any factors (clinical signs and symptoms or
3 patient reported outcomes) that would predict increased benefits or harms from
4 interventional treatments for varicose veins?
Varicose veins Interventional RCTs, SRs and Observational All years - 17/10/2012
treatments AND risk studies* [Medline and
factors Embase only]
6 *Observational search filter in F.1.3 expanded for this question

1. Vascular surgical procedures/
2. Ablation techniques/
3. Laser therapy/
4. Sclerotherapy/
5. Sclerosing solutions/
6. Sodium tetradecyl sulfate/
7. (scleros* or sclerotherap* or sclero therap* or UGFS).ti,ab.
8. (polidocanol or POL or sodium tetradecyl or STS or sotradecol or fibrovein or sclerovein).ti,ab.
9. (foam or microfoam or liquid).ti,ab.
10. (strip* or cryostrip* or saphenect* or disconnect*).ti,ab.
11. (avuls* or phlebectom* or microphlebectom* or miniphlebectom* or trans illuminate* or
transilluminate* or trivex).ti,ab.
12. surg*.ti.
13. (ablat* or endoluminal or laser or radiofrequency or radio frequency or endovenous or RFA or
EVLT).ti,ab.
14. or/1-13
15. Risk factors/
16. Risk assessment/
17. exp Treatment outcome/
18. Prognosis/
19. Disease progression/
20. (risk* or benefit* or harm* or predisp* or pre dispos* or prognos* or course* or progress* or
predict* or characteristic* or factor*).ti,ab.
21. (age or gender or sex or BMI or heredity or weight or body mass or family history or obes* or
pregnan* or birth or childbirth or lifestyle or occupation or contracept* or mobility or smoking
or drinking or co-morb* or comorb* or reflux).ti,ab.
22. or/15-21
23. 14 and 22

1. Phlebectomy/
2. Sclerotherapy/
3. Sclerosing agent/
4. Tetradecyl sulfate sodium/
5. Polidocanol/

86
6. Vein stripping/
7. Laser surgery/
8. Radiofrequency ablation/
9. Endovenous laser ablation/
11. (scleros* or sclerotherap* or UGFS).ti,ab.
14. (strip* or cryostrip* or saphenect* or disconnect*).ti,ab.
15. (ablat* or endoluminal or laser or radiofrequency or radio frequency or endovenous or RFA or
EVLT).ti,ab.
16. surg*.ti.
17. or/1-16
18. risk.hw.
19. predict*.hw.
21. Treatment failure/
22. Treatment response/
23. Prognosis/
24. Disease course/
25. (risk* or benefit* or harm* or predisp* or pre dispos* or prognos* or course* or progress* or
predict* or characteristic* or factor*).ti,ab.
26. (age or gender or sex or BMI or heredity or weight or body mass or family history or obes* or
pregnan* or birth or childbirth or lifestyle or occupation or contracept* or mobility or smoking
or drinking or co-morb* or comorb* or reflux).ti,ab.
27. or/18-26
28. 17 and 27

#1. MeSH descriptor Vascular Surgical Procedures, this term only
#2. MeSH descriptor Ablation Techniques, this term only
#3. MeSH descriptor Laser Therapy, this term only
#4. MeSH descriptor Sclerotherapy, this term only
#5. MeSH descriptor Sclerosing Solutions, this term only
#6. MeSH descriptor Sodium Tetradecyl Sulfate, this term only
#7. (scleros* or sclerotherap* or "sclero therapy" or UGFS):ti,ab
#8. (polidocanol or POL or "sodium tetradecyl" or STS or sotradecol or fibrovein or
sclerovein):ti,ab
#9. (foam or microfoam or liquid):ti,ab
#10. (strip* or cryostrip* or saphenect* or disconnect*):ti,ab
#11. (avuls* or phlebectom* or microphlebectom* or miniphlebectom* or "trans illuminated" or
transilluminate* or trivex):ti,ab
#12. (ablat* or endoluminal or laser or radiofrequency or "radio frequency" or endovenous or RFA
or EVLT):ti,ab
#13. surg*:ti
#14. (#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13)

87
#15. MeSH descriptor Risk Factors, this term only

#16. MeSH descriptor Risk Assessment, this term only
#17. MeSH descriptor Treatment Outcome explode all trees
#18. MeSH descriptor Prognosis, this term only
#19. MeSH descriptor Disease Progression, this term only
#20. (risk* or benefit* or harm* or predisp* or "pre disposed" or "pre disposition" or prognos* or
course* or progress* or predict* or characteristic* or factor*):ti,ab
#21. (age or gender or sex or BMI or heredity or weight or "body mass" or "family history" or obes*
or pregnan* or birth or childbirth or lifestyle or occupation or contracept* or mobility or
smoking or drinking or co-morbidity or comorbidities or comorb* or reflux):ti,ab
#22. (#15 or #16 or #17 or #18 or #19 or #20 or #21)
#23. (#14 and #22)
1 F.3.3 Assessment for treatment

2 The following two questions were searched using a single strategy:
3 Q1. Does the use of duplex ultrasound during assessment improve outcome after
4 interventional treatment compared to no duplex scanning in people with leg varicose
5 veins?
6 Q2. What is the diagnostic accuracy of hand held Doppler (HHD) compared to gold standard of
7 duplex scanning when used in patients with varicose veins?
Varicose veins Duplex ultrasound Diagnostic accuracy [Medline All years – 17/10/2012
and Embase only]

1. exp Ultrasonography, Doppler/
2. Ultrasonography, Interventional/
3. (ultraso* or echograph* or sonogra* or Doppler or duplex or DU or DUS).ti,ab.
4. or/1-3

1. Echography/
2. Doppler echography/
3. Endoscopic echography/
4. Color ultrasound flowmetry/
5. Diagnostic imaging/
6. (ultraso* or echograph* or sonogra* or Doppler or duplex or DU or DUS).ti,ab.
7. or/1-6

#1. MeSH descriptor Ultrasonography, Doppler explode all trees
#2. MeSH descriptor Ultrasonography, Interventional, this term only
#3. (ultraso* or echograph* or sonogra* or Doppler or duplex or DU or DUS):ti,ab
#4. (#1 or #2 or #3)
#5. MeSH descriptor Sensitivity and specificity explode all trees

88
#6. MeSH descriptor Prognosis, this term only

#7. MeSH descriptor Treatment outcome, this term only
#8. MeSH descriptor Likelihood functions, this term only
#9. (sensitivity or specificity):ti,ab
#10. (("pre test" or pretest or "post test") NEXT probability):ti,ab
#11. (prognos* or predict*):ti,ab
#12. (PPV or NPV):ti,ab
#13. ("ROC curve*" or AUC):ti,ab
#14. (diagnos* NEAR/2 (performance* or accurac* or utilit* or value* or efficien* or
effectiveness)):ti,ab
#15. "gold standard":ab
#16. (improve* NEAR/3 (outcome* or result*)):ti,ab
#17. (#5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16)
#18. (#4 and #17)
1 F.3.4 Conservative management

2 The following four questions were searched using a single strategy:
3 Q1. What is the clinical and cost effectiveness of compression therapy compared with no
4 treatment or lifestyle advice in people with leg varicose veins?
5 Q2. What is the clinical and cost effectiveness and safety of compression therapy compared
6 with foam sclerotherapy in people with leg varicose veins?
8 with stripping surgery in people with leg varicose veins?
10 with endothermal ablation in people with leg varicose veins?
Varicose veins Compression therapy RCTs, SRs and Observational All years - 17/10/2012
studies [Medline and Embase only]

1. Pressure/
2. Bandages/
3. exp Compression bandages/
4. Intermittent pneumatic compression devices/
5. ((compressi* or pressure) and (hosiery or stocking* or bandag*)).ti,ab.
6. ((compressi* or pressure or hosiery or stocking* or bandag*) adj2 (therap* or treatment* or
device* or eccentric or pneumatic)).ti,ab.
7. ((elastic or system* or support) adj2 (hosiery or stocking* or bandag*)).ti,ab.
8. (external* adj2 compression).ti,ab.
9. conservative treatment*.ti,ab.
10. or/1-9

1. Compression/

89
2. exp Compression therapy/

3. Compression bandage/
4. *Bandage/
5. Compression garment/
6. Intermittent pneumatic compression device/
12. or/1-11

S1 (MH "Compression therapy")
S2 (MH "Compression garments")
S3 (compressi* or pressure) and (hosiery or stocking* or bandag*)
S4 (compressi* n2 therap*) or (compressi* n2 treatment) or (compressi* n2 device*) or
(compressi* n2 eccentric) or (compressi* n2 pneumatic) or (pressure n2 therap*) or (pressure
n2 treatment)
S5 (elastic n2 hosiery) or (elastic n2 stocking*) or (elastic n2 bandag*) or (system n2 hosiery) or
(system n2 stocking*) or (system n2 bandag*) or (support n2 hosiery) or (support n2
stocking*) or (support n2 bandag*)
S6 external* n2 compression
S7 conservative treatment*
S8 S1 or S2 or S3 or S4 or S5 or S6 or S7

#1 MeSH descriptor Pressure, this term only
#2 MeSH descriptor Bandages, this term only
#3 MeSH descriptor Compression Bandages explode all trees
#4 MeSH descriptor Intermittent Pneumatic Compression Devices, this term only
#5 ((compressi* or pressure) and (hosiery or stocking* or bandag*)):ti,ab
#6 ((compressi* or pressure or hosiery or stocking* or bandag*) NEAR/2 (therap* or treatment*
or device* or eccentric or pneumatic)):ti,ab
#7 ((elastic or system* or support) NEAR/2 (hosiery or stocking* or bandag*)):ti,ab
#8 (external* NEAR/2 compression):ti,ab
#9 (conservative NEXT treatment*):ti,ab
#10 (#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9)
3 F.3.5 Interventional treatment
4 F.3.5.1 Stripping surgery
6 Q1. What is the clinical and cost effectiveness and safety of stripping surgery compared with
7 foam sclerotherapy in people with truncal leg varicose veins?

90
1 Q2. What is the clinical and cost effectiveness and safety of stripping surgery compared with
2 endothermal ablation in people with truncal leg varicose veins?
Varicose veins Stripping surgery RCTs and SRs [Medline and All years - 17/10/2012
Embase only]

1. Vascular surgical procedures/
2. (strip* or cryostrip* or saphenect*).ti,ab.
3. surg*.ti.
4. or/1-3

1. Vein stripping/
2. (strip* or cryostrip* or saphenect*).ti,ab.
3. surg*.ti.
4. or/1-3

#1 MeSH descriptor Vascular Surgical Procedures, this term only
#2 (strip* or cryostrip* or saphenect*):ti,ab
#3 (#1 or #2)
7 F.3.5.2 Sclerotherapy
8 Q. What is the clinical and cost effectiveness of foam sclerotherapy compared with
9 endothermal ablation in people with truncal leg varicose veins?
Varicose veins Sclerotherapy RCTs, SRs and Observational All years – 17/10/2012

1. Sclerotherapy/
2. Sclerosing solutions/
3. Sodium tetradecyl sulfate/
7. or/1-6

1. Sclerotherapy/
2. Sclerosing agent/
3. Tetradecyl sulfate sodium/
4. Polidocanol/

91

8. or/1-7

#1 MeSH descriptor Sclerotherapy, this term only
#2 MeSH descriptor Sclerosing solutions, this term only
#3 MeSH descriptor Sodium tetradecyl sulfate, this term only
#4 (scleros* or sclerotherap* or UGFS):ti,ab
#5 (polidocanol or POL or sodium tetradecyl or STS or sotradecol or fibrovein or sclerovein):ti,ab
#6 (foam or microfoam or liquid):ti,ab
#7 (#1 or #2 or #3 or #4 or #5 or #6)
2 F.3.5.3 Avulsion surgery
4 Q1. What is the clinical and cost effectiveness of avulsion surgery compared with sclerotherapy
5 in people with tributary leg varicose veins?
6 Q2. What is the clinical and cost effectiveness of truncal treatment accompanied by tributary
7 treatment (avulsion or sclerotherapy) compared with truncal treatment alone in people
8 with leg varicose veins?
Population Intervention Study filters used Date parameters
Varicose veins Avulsion surgery RCTs, SRs and Observational All years - 17/10/2012

2. (stab or hook*).ti,ab.
3. ((ambula* or minim* invasive) adj3 surg*).ti,ab.
4. (branch* adj2 (venous or vein or varicos*)).ti,ab.
5. tributar*.ti,ab.
6. or/1-5

1. Phlebectomy/
3. (stab or hook*).ti,ab.
4. ((ambula* or minim* invasive) adj3 surg*).ti,ab.
5. (branch* adj2 (venous or vein or varicos*)).ti,ab.
6. tributar*.ti,ab.
7. or/1-6

#1 (avuls* or phlebectom* or microphlebectom* or miniphlebectom* or trans illuminate* or
transilluminate* or trivex):ti,ab

92
#2 (stab or hook*):ti,ab
#3 ((ambula* or minim* invasive) NEAR/3 surg*):ti,ab
#4 (branch* NEAR/2 (venous or vein or varicos*)):ti,ab
#5 tributar*:ti,ab
#6 (#1 or #2 or #3 or #4 or #5)
1 F.3.6 Compression post treatment

2 Q. What is the clinical and cost effectiveness of compression post-ablative treatment
3 compared with ablative treatment alone in people with truncal leg varicose veins?
Varicose veins Compression therapy RCTs, SRs and Observational All years - 17/10/2012

1. Pressure/
2. Bandages/
3. exp Compression bandages/
4. Intermittent pneumatic compression devices/
10. or/1-9

1. Compression/
2. exp Compression therapy/
3. Compression bandage/
4. *Bandage/
5. Compression garment/
6. Intermittent pneumatic compression device/
12. or/1-11

S1 (MH "Compression therapy")
S2 (MH "Compression garments")
S3 (compressi* or pressure) and (hosiery or stocking* or bandag*)
S4 (compressi* n2 therap*) or (compressi* n2 treatment) or (compressi* n2 device*) or

93
(compressi* n2 eccentric) or (compressi* n2 pneumatic) or (pressure n2 therap*) or (pressure

n2 treatment)
S5 (elastic n2 hosiery) or (elastic n2 stocking*) or (elastic n2 bandag*) or (system n2 hosiery) or
(system n2 stocking*) or (system n2 bandag*) or (support n2 hosiery) or (support n2
stocking*) or (support n2 bandag*)
S6 external* n2 compression
S7 conservative treatment*
S8 S1 or S2 or S3 or S4 or S5 or S6 or S7

#1 MeSH descriptor Pressure, this term only
#2 MeSH descriptor Bandages, this term only
#3 MeSH descriptor Compression Bandages explode all trees
#4 MeSH descriptor Intermittent Pneumatic Compression Devices, this term only
#5 ((compressi* or pressure) and (hosiery or stocking* or bandag*)):ti,ab
#6 ((compressi* or pressure or hosiery or stocking* or bandag*) NEAR/2 (therap* or treatment*
or device* or eccentric or pneumatic)):ti,ab
#7 ((elastic or system* or support) NEAR/2 (hosiery or stocking* or bandag*)):ti,ab
#8 (external* NEAR/2 compression):ti,ab
#9 (conservative NEXT treatment*):ti,ab
#10 (#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9)
2 F.4 Economic searches

3 F.4.1 Economic reviews
4 Economic searches were run in Medline and Embase by combining the standard population with an
5 economic filter, and limiting by date range (see table below). Economic searches were executed in
6 the HEED and Cochrane (NHS EED and HTA) databases by running a standard population without
7 date limitation. Search terms for the HEED database are given below (for Cochrane population see
8 F.2).
Population Study filter used Date parameters
Varicose veins Economic [Embase and • 2009 - 17/10/2012 (Medline and
Medline] Embase)
• All years - 17/10/2012 (NHS EED, HTA
and HEED)
10 HEED search terms

1. AX=varicos* AND vein*
2. AX=sapheno* AND vein*
3. AX=venous AND insufficien*
4. CS=1 OR 2 OR 3
11 F.4.2 Quality of life reviews

12 Quality of life (QOL) searches were run in Medline and Embase by combining the standard
13 population with the QOL filter (F.1.5) without date limitation.

94
Population Study filter used Date parameters

Varicose veins QOL All years – 17/10/2012

95
Evidence tables clinical studies
1 Appendix G: Evidence tables clinical studies

2

96
1 G.1 Chapter 5 – patient perceptions and expectations

2 Table 15: Bobridge 201127
Reference Study type No. of patients Patient characteristics Methodology Source of

funding
Bobridge A, Observational 30 originally 15 women, 11 men; mean (range) age: Patients given baseline questionnaires: None
Sandison S, before-after study. recruited. 3 71.8 (38-90); health Education Impact Questionnaire reported
Paterson J, Because of the lack withdrew due to CEAP stages: (HEIQ), measuring the participants
Puckridge P, of a control group significant health • C3: 11.5%, chronic venous insufficiency (CVI)
Esplin M. A pilot the findings of this problems and one knowledge; they were also given the
• C4: 38.5%,
study of the study are prone to withdrew with time CIVIQ.
development considerable threats management • C5: 30.8%,
and to internal validity. issues. 26 thus • C6: 19.2%; The patients were then given an
implementation started the study. information booklet, which had been
Current treatment:
of a ‘best Setting: Australian developed on the best available
97
General Hospital. At the 6 month • compression stockings - 69.2%, evidence from the literature; it
practice’ patient
follow-up a further • compression bandages – 30.8%, contained lay term information on the
information
booklet for 3 withdrew due to • moisturising skin – 26.1%, pathophysiology of CVI and the
patients with significant health • leg exercises – 15.4%, importance of skin care, leg elevation,
chronic venous problems and 3 exercise, diet and compression
• leg elevation – 3.8%;
insufficiency. were lost to follow- garments. The information booklet
up: 20 were thus median 24 month duration of chronic had been amended after consultations
Phlebology venous insufficiency (CVI) (range 0.25-684
2011; 26: 338- left for analysis at 6 with vascular clinicians. A vascular
months. This was a months); nurse specialist gave the booklet, and
343
per-protocol most common causes of CVI were explained its contents. The participant
analysis. superficial and deep perforator was asked to take the information
incompetence, and superficial great booklet home, to read through the
saphenous and deep incompetence information, and to undertake the
(15.4% each); recommended best practice activities
co-morbidities: in their home environment over the
• hypertension (50%), next 6 month period. No other
• type II diabetes (15.4%), intervention was given, though it is
assumed (unclearly reported) that
Reference Study type No. of patients Patient characteristics Methodology Source of

funding
• thyroid dysfunction (15.4%); patients were allowed to continue
• BMI range 20-35.4 (mean 30.8). their current treatment regimens (as
described in patient characteristics
Inclusion: Duplex evidence of reflux, with column).
a CAEP of C3-C6.
Further measurements (HEIQ and
Exclusion: Leg swelling due to cardiac, CIVIQ) were taken at 1 and 6 months
renal or hepatic dysfunction, post-booklet allocation via the
lymphodema, lipoedema, DVT, cellulitis, telephone.
cancer or post-op swelling; diminished
mental cognition; physical disability.
Results: The paper gives descriptive results only. P values given but no event rates.
1 month post booklet implementation (n=26)

98
There were significant improvements in participants performing at least one activity to improve their CVI (p=0.01), monitoring their CVI (p=0.045), knowing things
which could trigger their CVI and make it worse (p=0.005), having effective ways to prevent their CVI symptoms from limiting what they can do (p=0.045). There were
also improvements in the ability to travel by car or bus (p=0.05), undertaking social activities (p=0.03) and feeling less embarrassed about showing their legs (p=0.025).
6 months post booklet implementation (n=20)
During the time between 1 and 6 months, there was a significant reduction in the number of people worrying about CVI (p=0.012) and feeling embarrassed about
showing their legs (p=0.005), as well as being able to climb several flights of stairs (p=0.008)
At 6 months, there were also significant improvements in performing at least one activity to improve CVI (p=0.003), knowing things which could trigger CVI and make it
worse (p=0.016), having effective ways to prevent CVI symptoms limiting what they can do (p=0.008), worrying about their CVI (p=0.03) and feeling a sense of
hopelessness about their CVI (p=0.007). there was also a significant improvement in leg and ankle pain (p=0.038), ability to do domestic chores (p=0.017), feeling
nervous and tense (p=0.026) and feeling embarrassed about showing their legs (p=0.008).
1
1 Table 16: Campbell 200641
Reference Study type No. of patients Patient characteristics Methodology Source of funding
Campbell WB, Quantitative 203 patients Patients referred to a Patients who were due to attend the vascular clinic were sent None reported
Decaluwe H, cross- initially sent in vascular unit with questionnaires beforehand, and asked to bring them in
MacIntyre JB, sectional their “uncomplicated completed for clinic. No reminders were given, and no
Thompson JF, questionnaire questionnaires – varicose veins”. 75% patient was asked to complete a questionnaire after receiving
Cowan AR. Most study. a 62% response female; median age 51 advice in clinic.
patients with rate. 13 were (range 20-83).
varicose veins Setting: later excluded The questionnaire contained 13 questions about symptoms
have fears or unclear but due to 8 not and future expectations. The questions relevant to future
concerns about likely to be a having varicose expectations were:
the future, in vascular unit veins, 3 having • Have you any other concerns, worries or
addition to their in an NHS ulcers and 2 fears about your varicose veins? Yes/No
presenting secondary having phlebitis. • If yes, what are they?
symptoms. Eur J care trust. Hence 190 • Are you worried that your varicose veins
Vasc Endovasc participated in might cause you medical harm? Yes/No
Surg 2006; 31: the study. • If yes, what exactly are you worried about?
99
332-334.
Results:
Negative expectations about prognosis

• 150/190 (79%) reported that they had concerns, worries or fears about their varicose veins:
• 59/190 (31%) feared future thrombosis
• 30/190 (16%) feared future trauma/bleeding
• 28/190 (15%) feared future ulcers
• 22/190 (12%) feared future circulatory disease
• 8/190 (4%) feared future phlebitis
• 57/190 (30%)had general concerns about the future, particularly if there was a family history of varicose veins.
These worries contrasted with the answers to another question on the questionnaire, which asked about their reason for seeking medical advice: only 27/173 (16%)
stated concerns about the future.
How can these expectations be addressed?

The authors suggested that “good explanation (both verbal and written) about the nature and prognosis of varicose veins should be a routine part of good patient
management. Reassurance against the likelihood of a benign prognosis leads many to decide against treatment, especially if they understand they can return in future.
We do not know which patients will go on to develop skin problems or ulceration, but clinical experience suggests that the proportion is small and patients should be
told the warning signs of eczema or darkening of the skin at the ankle.”
1
100
1 Table 17: Darvall 200965
Reference Study type No. of Patient characteristics Methodology Source of funding

patients
Darvall KAL, Quantitative 351 patients Consecutive patients A questionnaire was given one week prior to foam None reported
Bate GR, cross- (464 legs). undergoing foam sclerotherapy treatment. The questionnaire responses were
Sam RC, sectional sclerotherapy for on a 5 point Likert scale (an awful lot, a lot, quite a bit, a little,
Adam DJ, questionnaire 80% response symptomatic varicose veins. not at all), which was later collapsed to 3 categories: “a
Silverman study. rate for the Patients had been referred for significant improvement”, “quite a bit” and “not at all” (the
SH, expectations treatment by their GPs to NHS paper uses the term “moderate” in the results section, which
Bradbury Setting: Large questionnaire. vascular surgeons at a single presumably means “quite a bit”). The patient could also
AW. NHS hospital. indicate if a question was not applicable. The questionnaire
Patients’ secondary was given for each leg to be treated (so a bilaterally affected
expectations care trust 35% male; 25% had recurrent patient would do two questionnaires).
before and disease; 67% had CEAP 2-3;
satisfaction 33% had CEAP 4-6; all had Section 1 asked about the expected improvements in
after symptomatic primary varicose symptoms (pain or aching, itching, tingling, restless legs,
ultrasound veins; 97% had superficial cramps, swelling and heaviness).
101
guided foam venous reflux only and 3%

had both superficial and deep Section2 asked about expected improvements in
sclerotherap
reflux; all were secondary to appearance, lifestyle (choice of clothes, work performance,
y for
reflux not obstruction. social and leisure activities and relationships.
varicose
veins. Eur J [In addition a post treatment questionnaire was given 6
Treatment was for the great
Vasc months after treatment to ascertain actual subjective
saphenous vein (76% of
Endovasc improvements in all these areas, using the same response
patients), small saphenous
Surg 2009; categories. Integration of responses from the pre and post
vein (10%) and a combination
38: 642-647. treatment questionnaires allowed estimation of whether
of great saphenous vein, small
saphenous vein and anterior expectations were met.]
accessory saphenous vein
(14%).
Results:
Symptom expectations
A significant improvement in symptoms was expected in approximately 33% of legs, and a moderate improvement in 67%.

patients
[Depending on the symptom, between 49% and 63% of legs had significant improvement in symptoms at 6 month post-treatment and about 10% had no improvement
at all. Overall, expectations were met or exceeded in 80% legs.]
The detailed expectations data for individual symptoms are given below (the percentage figures are approximate as extrapolated from low resolution table)
Symptom Expectation of significant improvement (%) Expectation of moderate improvement (%)
pain 37 63
itch 32 68
tingling 24 76
cramp 30 70
restless legs 29 71
swelling 37 63
heaviness 37 63
Percentages where pre-operative expectations were not met 6 months post-operatively
102
Factor Legs [n=365] or patients [n=281] where expectations were not met
Symptoms Pain 20%
Itch 21%
Tingling 18%
Cramp 23%
Restless legs 22%
Swelling 27%
Heaviness 18%
Other factors Appearance of the legs 12%
Choice of clothes that can be worn 25%
Performance at work 25%
Relationships 14%
Enjoyment of leisure activities 30%
Cosmetic expectations
Over 60% of patients expected a significant improvement in the appearance of their legs (a further 30% expected a moderate improvement).

patients
[96% actually noticed a significant improvement at 6 months.]
Life-style benefits expectations
Approx. 30% of patients expected significant improvement in the choice of clothes, and a further 40% expected moderate improvement.
[75% of patients met or exceeded these expectations]
Approx. 27% of patients expected significant improvement in performance at work, and a further 40% expected moderate improvement.
Approx. 27% of patients expected significant improvement in leisure activities, and a further 40% expected moderate improvement.
Relationships expectations
103
10% of patients expected significant improvement in relationships, and a further 15% expected moderate improvement.
[>50% actually experienced such improvements.]
Factors affecting expectations
Cosmetic and social expectations did not depend on whether a patient had had previous varicose veins surgery. Younger age (<55yrs) and CEAP stage C2 disease were
each related to higher expectations of cosmetic improvements. Women and C2 patients had higher expectations in terms of clothes choice. Work, relationships and
social/leisure expectations were not related to any measured factors.
1
2
1 Table 18: Dillon 200582
Reference Study type No of patients Patient Methodology Source of

characteristics funding
Dillon MF, Carr Quantitative 82 given the original Patients with newly The initial written questionnaire was given at the first None reported
CJ, Feeley TMF, questionnaire questionnaire, and all diagnosed varicose vascular clinic appointment. It is unclear if this was given
Tierney S. study carried out 82 completed it. veins referred to before or after the consultation, but, given the
Impact of the in Republic of 67/82 completed the randomly selected questionnaires purpose of evaluating initial expectations, it
informed Ireland. telephone interview vascular clinics for appears likely it was before the consultation. This because
consent process 2 weeks post- surgery. 57 females; the consultation included an in-depth discussion of the
on patients’ Setting: randomly information provision median age (range) nature and consequences of surgery; furthermore,
understanding selected vascular (pre surgery) and of 46 (17-72) years; immediately after the consultation the patient was given a
of varicose clinics in Republic reasons for drop-out 37/82 had completed leaflet reiterating this information. This questionnaire
veins and their of Ireland. are not given. secondary education. assessed the expectations of the outcome of surgery and
treatment. Irish the perception of threats to health from varicose veins.
Journal of
medical science Two weeks later (but before the surgery itself) the patients
2005; 174: 23- were given a repeat of the initial questionnaire (but in
104
27 telephone interview form in all but one case) to assess the

effects of the discussion and leaflet on expectations
Results:
Expectations about varicose vein risks

• 46/82 initially believed that they were at “high risk” of developing ulcers. Two weeks after information giving this figure was 40/67.
• 41/82 initially believed that they were at “high risk” of developing DVT. Two weeks after information giving this figure was 33/67.
• 26/82 initially believed that they were at “high risk” of bleeding from minor injuries. Two weeks after information giving this figure was 45/67.
• 27/82 initially believed that they were at “high risk” of developing gangrene. Two weeks after information giving this figure was 19/67.
34/82 initially stated that their varicose veins caused them “significant personal anxiety”.
Expectations of surgery
(% given for results of telephone questionnaire in paper, which cannot be converted to a fraction due to uncertainty in the value of the denominator)
• 66/82 initially believed that surgery will improve appearance. Two weeks after information giving this figure was 90%.
• 63/82 initially believed that surgery will improve pain. Two weeks after information giving this figure was 84%
Reference Study type No of patients Patient Methodology Source of

characteristics funding
• 62/82 initially believed that surgery will improve itch. Two weeks after information giving this figure was 80%.
• 63/82 initially believed that surgery will improve heaviness. Two weeks after information giving this figure was 86%.
• 55/82 initially believed that surgery will improve flares. Two weeks after information giving this figure was 31%.
Other expectations
• 57/72 initially believed that recovery after surgery would take < 2 weeks. Two weeks after information giving this figure was 44/62.
• 15/72 initially believed that return to work after surgery would take a month. Two weeks after information giving this figure was 17/62.
Recall of complications at the telephone interview was poor – only 18/67 could name any adverse effects. 50/67 remembered getting the educational leaflet, and recall
of complications was significantly more likely in those who recalled getting the leaflet.
Author summary: Patients attending varicose veins clinics have an unrealistic expectation of the benefits of surgery and fail to understand the benign nature of their
condition. The outpatient [information-giving] process has little effect on patient-held beliefs.
1
105
2
1 Table 19: Palfreyman 2004199

patients
Palfreyman Qualitative 16 recruited Patients who had been referred for Interviews were conducted 5-14 days after attendance Northern General
SJ, Drewery- study. by a research varicose vein specialist investigation at a surgical outpatient clinic. Interviews were semi- Nursing and PAMs
Carter K, nurse. by their GPs. Reasons for seeking structured and conducted in a quiet room within the Research Grant –
Rigby K, Setting: a referral from GPs were primarily for hospital setting. The interviews were tape-recorded no conflict of
Michaels JA, large NHS 22 were relief of symptoms. and lasted 30-45 minutes. interest likely.
Tod AM. secondary approached
Varicose care trust in but 6 were Inclusion: patients with varicose The anonymous and transcribed transcripts were
veins: a Sheffield. unable to veins who were referred for entered into a qualitative software package
qualitative participate specialist assessment/treatment. (qrsNVIVO). Framework analysis used to identify
study to due to other thematic frameworks.
commitments. Exclusion: Serious complications
explore
Purposive such as ulcers or bleeding; significant Trustworthiness of the data was reported as
expectations
sampling was risk factors such as DVT or fractures. “ensured” by the use of:
and reasons
used to get • framework analysis
for seeking
106
Baseline Characteristics: 3 males and • on-going reflection and discussion

treatment. patients of
13 females; age from 20-76; length amongst researchers (but no mention of
Journal of both genders,
of time with varicose veins 4-51 formal triangulation methods)
Clinical and a range of
years; previous treatments were • Interpretation of emerging issues
Nursing ages.
none (n=7), compression (n=6), were tested by feedback to the patient during
2004; 13: surgery (n=2), sclerotherapy (n=1).
332-340. the interview
The treatment outcome was surgery
• Analysis and interpretation from
(n=13) and conservative treatment
earlier interviews were tested in subsequent
(n=3).
interviews
• The anonymous transcripts and key
themes were shown to a subset of
interviewees to check validity of findings
Results:
Expectations
Positive expectations

patients
Positive expectations of treatment effects on the level current symptoms
Patients generally had an expectation that something could be done about their symptoms.
“…more than anything is that it won’t be as it is now, so that the pain factor, the heaviness, everything that goes with it hopefully will have gone…”
Although an expectation of cosmetic improvement was also present, this expectation was not the main reason for seeking treatment.
Positive expectations of prognosis if treated

There was an expectation that surgery would prevent future deterioration of symptoms and extent of varicose veins.
Patients either had the expectation of no possibility of recurrence, or that even a short symptom free period would be worth it.
Even those with previous surgery expected that their surgery this time would work better, and that even a short symptom free period would be worth it.
Negative expectations
Negative expectations of prognosis if untreated
An important motivation for treatment was that DVT and ulceration could occur later because of their varicose veins. A particular concern was that varicose veins might
107
exacerbate the risks of developing a DVT whilst flying.
Negative expectations about adverse events of surgery
Fear of surgery was common:
“….I’m in the middle now. I’m frightened of having them done and I’m frightened of having them….”
How can these expectations be addressed?
Consideration of patient expectations should influence the nature of the nurses’ assessment and information giving.
Author’s summary: “….they had actively sought treatment from the health service, with the expectation that they will gain symptom relief…this wish for their
symptoms to be relieved by treatment might be an unrealistic expectation, as the evidence suggests that surgery in particular may not have any effect on the
symptoms experienced in the leg with varicose veins……The patients, in seeking to relieve their symptoms, were after an immediate benefit. This belief meant that they
disregarded the potential risks of treatment… the participants were also being unnecessarily anxious about the complications of varicose veins….such worries were not
supported by the evidence….patients over-estimate the extent to which the appearance of their legs can be improved by treatment…..”
1
1 Table 20: Shepherd 2010247
Shepherd AC, Gohel MS, Cross-sectional 111. Consecutive patients Patients were invited to None reported
Lim CS, Hamish M, Davies questionnaire survey. referred to one complete an anonymous
AH. The treatment of 83 gave complete consultant vascular questionnaire prior to
varicose veins: an Setting: vascular clinic in responses and the surgeon with their consultation (and
investigation of patient an NHS secondary care remaining 28 gave partial symptomatic varicose prior to any information
preferences and trust. responses. veins; 73% of patients being given out).
expectations. Phlebology were female; 43% were Questions related to
2010; 25: 54-65. unemployed, and 17% occupation, physical
were part-time symptoms and impact of
employees; age range 18- the varicose veins,
83; reported co- patient knowledge of
morbidities were: existing treatments,
• hypertension - 16% concerns about
complications and
• previous deep vein
recurrence, preferred
108
thrombosis – 7%
treatment options and
• asthma – 5% factors that might
• diabetes – 4% influence decisions
• epilepsy - 2% regarding treatment.
• Chronic obstructive
pulmonary disease
(COPD) – 2%
• Ischeamic heart
disease (IHD) – 2%
• Transient ischaemic
attacks (TIAs) – 1%
• No co-morbidities –
61%
Results:
Negative expectations about varicose veins treatments

The main concerns that patients had about treatment were presented in a low resolution figure, and so exact data are unclear. However, it appears that about 35%
were “extremely concerned” about recurrence, and about 16% were “extremely concerned” about discomfort after treatment
Awareness of treatment options

• 86% aware of surgery as an option
• 32% were aware of laser ablation
• 22% were aware of sclerotherapy
• 18% were aware of radiofrequency ablation.
• 10% were unaware of any treatments.
24/103 expressed a preference for endovenous treatments (i.e. endothermal ablation or foam sclerotherapy) over surgery. Of the endovenous treatments, laser was
the most popular (first choice of 11%). Most patients (74/103) stated that they didn’t know enough to express a treatment preference.
1
2
109
1 Table 21: Zubilewicz 2009290
Zubilewicz R, Chmiel- Cross-sectional survey. 156 Polish women with Participants were given a None reported
Perzynska I, Derkacz M, chronic venous disease multiple choice
Schabowski J. The Setting: Poland but no other (CVD) who had never questionnaire, which was
women’s span of details provided. been treated. Average aimed to assess
knowledge about chronic age was 44.5 (16) years. knowledge concerning
venous disease. Family 19% were <30 years old, modifiable risk factors for
Medicine and Primary 68% were between 31-65 chronic venous disease
Care Review 2009; 11: years old and 13% were and the presence of
919-922. over 65 years old. 14% symptoms. No other
had primary education, details given.
47% secondary education
or vocational training and
39% had a university
degree.
110
Results:
Expectations / preconceived ideas about modifiable risk factors
The following were the most often suggested risk factors for chronic venous disease. The figures given are the percentage of participants believing it was a risk factor:
• Overweight and obesity (85%)
• High heeled footwear (73%)
• Standing and sitting postures at work (71% and 61% respectively)
• Pregnancy (58%)
• Crossing legs (51%)
• Long journeys by car or plane (40%)
• Oral contraceptives (30%)
• Use of depilatory wax (17%)
• Under-floor heating (11%)
• Physical activity (20%)
>50% of respondents of <65 years assessed CVD as a severe disorder which lessened Quality of Life (QoL). Approximately 70% of women >65 years considered CVD as
especially serious.
33.3% were aware that CVD was a risk factor for ulceration.
Approximately 70% of women under 30 years regarded CVD as primarily a cosmetic problem.
The perception of CVD as a serious disease was higher in those with lower educational attainment.
1
2
111
G.2 Chapter 6 – referral from primary care
2 G.2.1 Risk factors associated with disease progression
3 Table 22: Boccalon 199728
Reference Study type No. of Patient characteristics Risk factors studied Outcome measures Length of Source of
patients follow-up funding
Boccalon H, Cross- 895, drawn Chronic venous Gender Development of skin NA Not stated
Janbon C, sectional, from all insufficiency of lower changes or ulcerative
Saumet JL, but regions of limbs, all of which had Age changes, in terms of
Tafani A, contained France. been treated with 2 being categorised in the
Secondary aetiology
Roux T, Vilain potentially These months of daily 1g three groups: Group 1:
C. useful included 229 microflavanoid fractions. no skin changes; group
Characteristic gender and who were 2: hyper-pigmentation
s of chronic existence of asymptomati Inclusion: >18; at least with no ulceration;
one symptom from
112
venous previous c and group 3: more severe

insufficiency thrombus without any heaviness, pain or night skin changes (included
in 895 aetiology detectable cramps attributable to “pre-ulcerative*”
patients findings signs. These CVi for at least 1 year; changes or ulceration).
followed in which will 229 are not worsened by prolonged
general also be included in standing or sitting, *not explained further.
practice. effectively this review warmth, and improved
International case- analysis. by elevation, activity or
Angiology control. compression; functional
1997; 16: discomfort had to be at
226-34 least 40/100 on a VAS.
Exclusion: arteriopathy
or neuropathy of the
lower limbs.
Results:
Gender
Group 1 had 33 men (age 51) and 278 women (age 44); group 2 had 25 men (age 54) and 269 women (age 53) and group 3 had 12 men (age 59) and 49 women (age
Reference Study type No. of Patient characteristics Risk factors studied Outcome measures Length of Source of
67).
For each group, the % of men and women were:
Group 1 (<C4) Group 2 (skin changes not including pre- Group 3 (more severe skin changes including pre-
ulceration or ulceration) ulceration or ulceration)
men 47.1% 35.7% 17.1%
women 46.6% 45.1% 8.2%
Secondary aetiology
The percentage with secondary CVI were: group 1: 3.2%; group 2: 9.9%; group 3: 27.9%. The paper reported that a previous episode of DVT was more commonly
reported in the history of patients with the most severe objective signs and that this was significant (p<0.001).
Age
The severity increased with age. Gp 1 were 45 (14) yrs, group 2 were 53 (15) yrs and Group 3 were 65 (13) years.
Other factors
Other factors were considered but they were cross-sectional and so do not indicate prognosis for progression.
113
1
2
1 Table 23: Pannier 2011202
Reference Study type No. of patients Patient characteristics Risk factors studied Outcome Length of Source of
measures follow-up funding
Pannier F, Prospective 3072 enrolled at Participants were sampled A standardised Progression 6.6 years Not stated
Rabe E. cohort baseline. 1978 randomly from the population questionnaire was used to from C2 to C3-
progression study remained in the study at aged 18-79 years living in Bonn collect information at 6 over the 6.6
of Chronic follow-up. (These were a and two rural townships. baseline on the following years
Venous cross-section of all risk factors:
Disorders: people, as varicose veins 3072 represented a response
• sociodemographic
Results from were not an inclusion rate of 59%. The age and
status
the Bonn criterion). gender were representative of
the general German population. • smoking
Vein Study.
Journal of The relevant figure is • alcohol
290, however, as this Inclusion: 18-79 years; German • physical activity
Vascular
represents the number nationality. [Note varicose veins
Surgery 2011; • blood pressure
with C2 at baseline (and or CVI were not an inclusion
53: 254-255 • medical history
who also attended at criterion]
114
follow-up). 432 had C2 • quality of life

Exclusion: hemiparesis/leg
at baseline, indicating • hormonal intake
amputations; severe illness;
very high attrition of 142 • contraceptive pill
moribund patients; systemic
participants. Reasons for • professional stress/
inactivating disease.
attrition not reported. work strenuousness
Baseline Characteristics: For • BMI
those attending at baseline,
• Heaviness
• 56.2% were male,
• Feeling of tension
• 33.6% were 18-39 years,
• Swelling feeling
• 37.4% were 40-59 years and
• Pain during prolonged
• 29% were 60-79 years. walking
• 43.9% had a BMI of <25. • Itching
• 9.6% were C0,
• 59% were C1,
• 14.3% were C2,
• 13.55 were C3,
• 2.9% were C4 and
• 0.7% were C5-6.
• 62.4% lived in urban areas.
No information reported on the

characteristics of the 290
relevant C2 participants
remaining at 6.6 year follow-up.
Results: ** These data has been removed as it is academic in confidence

Risk factor RR (95% CI) of the progression from C2 to C3-6
** These data has been removed as it is academic in
confidence
115
1
1 Table 24: Robertson 2009230
Reference Study type No. of patients Patient Risk factors studied Outcome Length of Source of
characteristics measures prospective funding
follow-up /
retrospective
recollection
Robertson L, Case control study, 381 patients were invited All subjects were Many “risk factors” in this study were Development Unclear, as None
Lee AJ, but cross-sectional to participate. Of these 38 recruited from the measured cross-sectionally. The only of ulceration patients were
Gallagher K et analyses included ascases and 103 controls did register of venous cross-sectionally measured risk factors versus no simply asked to
al. Risk factors well (see risk factorsnot respond or refused to patients scanned in a that did not present doubt about the ulceration. recollect activity
for chronic studied section). participate, leaving 240. vascular laboratory atdirection of cause-effect (if any), and data when aged
ulceration in This represents a response a large Scottish NHS were thus potentially informative, were 35-45 years – the
patients with Potential rate of 63%. trust, as well as GP gender, height and age (these could not time duration back
varicose veins: confounders such practices in a Scottish possibly be effects of ulceration, and to this would have
a case control as socioeconomic 120 were C6 or region. therefore were a cause, or correlating varied widely, and
study. J Vasc status were C5*[cases]. Of these, 24 with another, causative, factor). In some patients may
Surg 2009; matched, and other had had previous surgery. The cases were to contrast, cross-sectionally measured not have even
116
49:1490-8 confounders were Mean age of first have an open or factors where the cause-effect direction reached this age
adjusted for. developing an ulcer was healed ulcer (C5/6), (if any) was intrinsically unclear were: range.
56 (15.5) years [approx 8 and the ulcer was to BMI, weight, blood pressure, venous
The patients were years prior to study, on have been active for
pump power, ABPI, and existence of
recruited from the average] – this means any at least 8 weeks.
reflux in various veins (these could be
same source, and soretrospective recollections Subjects with ulcers
effects as well as causes). Smoking in
any bias arising of <8 years previously on the feet were the past year and activity in the past
from one group would be unlikely to be excluded to avoid year could be regarded as possibly
having a representative of true including diabetic or cross-sectional as many of those in the
systematically “causes”. Median (IQR) of peripheral vascular ulcer group are likely to have had ulcers
higher chance of 2(1-3) active episodes, diseasePVD patients. beginning more than a year before.
having any risk each of a mean (sd)
factor were duration of 7(13) years. The controls were Some factors were measured by asking
reduced. selected to have no the patient about past exposure to risk
120 were C4 or less history of leg ulcers. factors, and were therefore potentially
No efforts to ensure[controls].
informative. Such risk factors were
optimal recollection 16 patients had C1
physical activity between the ages of 35
of past exposure. Only one leg per subject disease only (10
and 45 and daily activity between the
follow-up /
retrospective
recollection
was used. If a patient werecases and 6 controls) ages of 35 and 45. However, a small
Poor attempt to bilaterally affected, only but were kept in the proportion (probably <25%) of patients
ensure direction of the worse affected leg wasanalysis on the basis were within those age groups at the
any cause-effect chosen for inclusion. that they formed a time of assessment and so, for those
was unambiguous. small percentage patients, these measures were cross-
* For those that are C5, it sectional. The cause-effect status of
No reports of is possible that they were smoking history was fairly clear given
blinding of C6 before any of the that the mean pack years were around
assessors. retrospective 16. Pre-ulcer weight was another
recollections. It is thus informative factor. Cause-effect was
Overall, very low
unclear whether this unclear for previous history of DVT/PE
quality.
paper meets inclusion or phlebitis as it was very unclear
criteria.
117
whether these were antecedents of

ulceration, or merely an uncongenial
accompaniment.
All ORs were adjusted for age and sex.

Results. ONLY results that pertain to risk factors that are likely to have preceded ulceration are included. Cross-sectional data (except for those where the possible
direction of cause-effect is fixed, such as gender) are not included as they are of no relevance to the issue of prognosis. Relevant univariable results (only adjusted for age
and sex) are given below.
Multivariable results are not given as no potentially prognostic factors remained in the model after stepwise removal. All the results presented here are univariate results.
Risk factor mean (sd) RF in casesmean (sd) of RF in P value

/ % with RF controls/ % with RF
Age 64.1(13.4) 59.9(11.7) 0.01
% male 55% 43% 0.07
b
Risk factor mean (sd) RF in casesmean (sd) of RF in OR (CI) [univariable in terms of no adjustment for other RF, except age and sex]
controls
follow-up /
retrospective
recollection
height 1.67(0.11) 1.67(0.1) 0.54(0.02-19.41)
Smoking pack years 4.47 (3.16-6.32) 4.1(2.45-5.48) 1.08(0.9-1.29)

b
Risk factor %with the RF in cases% with RF in controls OR (CI) [univariable in terms of no adjustment for other RF, except age and sex]
a
Physical exercise in past year
Nil 28.8 14.9 Reference
Light 35.6 42.1 0.44(0.21-0.91)
Mod 28.2 36.8 0.43(0.20-0.93)
Strenuous 6.8 6.1 0.70(0.20-2.41)
118
Physical exercise aged 35-45

Nil 15.3 14.0 Reference
Light 28 28.9 0.86(0.37-2.01)
Moderate 39.8 44.7 0.76(0.34-1.68)
Strenuous 16.9 12.3 1.29(0.48-3.49)
a
Daily activity in past year
sitting 35.6 17.5 Reference
walking 48.3 60.5 0.43 90.22-0.820
light loads 7.6 15.8 0.29(0.11-0.77)
heavy work 8.5 6.1 0.99(0.29-3.35)
Daily activity aged 35-45

sitting 16.1 14.9 Reference
walking 47.5 44.7 1.09(0.49-2.41)
follow-up /
retrospective
recollection
light loads 14.4 18.4 0.79(0.31-2.03)
heavy work 22.0 21.9 0.86(0.35-2.10)
Risk factor (RF) %with the RF in cases% with RF in controls P value

History of phlebitis 37 28 NS
History of leg fracture 18 11 NS
History of arthritis 40 35 NS
Ever smoked 63.6 45.6 0.009
1 (a) Unlikely to have preceded ulceration but included for completeness
2 (b) The OR is the odds ratio of ulceration for every additional increment of the continuous variable [adjusted for age and sex]
3
119
1 Table 25: Scott et al. 1995242
Scott TE,
Case control study, with 129 with Exclusion: <18 years; unable to speak Retrospective Existence of Unclear. The None stated
LaMorte
cross-sectional varicose veins English; unable to give informed consent. information on ulceration only
WW, Gorin
components. and 93 with potential risk factors retrospective
DR,
chronic venous Cases: Patients with class II or class III CVI, was done via a questions were
Menzoian Potential confounders such insufficiency cared for in vascular surgery clinics at a large structured interview, medical history
JO. Risk as socioeconomic status, “CVI”. All those medical centre in the USA. Unclear if all had by an interviewer and years
factors for age, BMI etc were not ulcers, but elsewhere in the paper they are blinded to the status
with CVI had smoked, and the
chronic matched. A multivariable ulceration. described as having ulceration. Diagnosis of the patients. distance back
venous analysis was performed There was also a based on visible appearance. into the past
insufficienc that adjusted for these These included
group of subjects these variables
y: a dual confounders, and it is Controls: Patients with varicose veins, medical history, years
with no venous occupied was
case- included in this review as it disease (used to attending the same clinic as the cases. of smoking, standing unspecified.
control predominantly contains at work and exercise
assess risks for CVI (with varicose veins
study. J risk factors that are levels. Of these,
initially
120
ulceration)
Vasc Surg potentially preceding standing at work and
developing
1995; ulceration. Age 59(1.6) 43.7(1.3) exercise were cross-
venous disease,
22:622-8 sectional and so not
so not relevant BMI 30.4(1) 25.6(0.5)
The patients were included in this
to this review
recruited from the same Male 58% 17.8% review.
question) that is
source, and so any bias
not included %white 51.6% 70.6%
arising from one group
here.
having a systematically
Mean 25990 (1080) 31825 (1398)
higher chance of having Rates of refusal estimated
any risk factor were were described family income
reduced. in US$ (sd)
as <5% and to be
the same across college 27.3% 52.6%
No efforts to ensure
the groups. education
optimal recollection of past
exposure. lack of 33.7% 19.4%
insurance
Assessor performing the
retrospective survey was
blinded to the group status
of the subjects.
Overall, very low quality.
Results: ONLY results that pertain to variables that are likely to have preceded ulceration are included. Cross-sectional data (except for those where the
direction of cause-effect is fixed, such as gender) are not included as they are of no relevance to the issue of prognosis. Relevant univariable results (only adjusted for age
and sex) are given below.
Risk factor CVI % Varicose vein % Significant difference? (p values not
stated)
History of heart disease 22.6% 4.6% Y
History of diabetes mellitus 22.6% 2.3% Y
History of hypertension 49.5% 16.3% Y
History of kidney disease 4.4% 2.3% N
121
History of arthritis 19.7% 13.9% N

History of leg injury 54.8% 17.8% Y
History of phlebitis/clot 45.6% 24.2% Y
History of oral contraceptive use 5.1% 20.7% Y
years smoked 17 (1.7) 8.8(1.0) Y
Multivariable analysis results
Risk factor OR for ulceration
age 1.07/yr (1.04-1.1)
male sex 8 (3.5-18.3)
2
BMI 1.07/kg/m (1.01-1.13)
no health insurance* 3.2 (1.3-7.7)
history of leg injury 4.7 (2.1-10.5)
Diabetes mellitus 4.3 (0.99-18.7)
1
1 G.2.2 Factors associated with response to treatment
2 Table 26: Fischer 200698

Reference Study type No of Patient characteristics Risk factors studied Outcome measures Length of Source of
Fischer R, Chandler JG, Prospective n=1261 Patients undergoing SFJ BMI, prior parity, Saphenofemoral Variable. All
Stenger D, Puhan MA, observation patients ligation and GSV stripping, interim pregnancy, reflux recurrence, follow-ups were
De Maeseneer MG, al study. /1638 limbs. from 1978 to 2003. deep venous using duplex, but, in after 1991.
Schimmelpfennig L. Main aim Unspecified insufficiency, age, earlier cases Categorised as 2-
Patient characteristics was to attrition, but Inclusion: Primary operations gender, side continuous wave 6 yrs, 7-12 yrs
and physician- evaluate sophisticate affected, diabetes doppler. Reflux had and > 12 years.
Exclusion: History of DVT, or
determined variables modifiers of d imputation mellitus. to last >0.5 seconds. follow-up
serious trauma to the affected
affecting treatment used. duration was
leg; procedures involving
saphenofemoral reflux success. normalised
crossectomy but not GSV
recurrence after through
stripping.
ligation and stripping adjustment in
of the great saphenous the multivariable
122
Baseline Characteristics:
vein. J Vasc Surg 2006; Mean age 49.7(12) at the time analysis. Mean
43: 81-7 of operation was 6.6(4.3)yrs.
Results:
BMI>29, prior parity, and interim pregnancy were all associated with an increased odds of reflux recurrence. The table below shows the results of the multivariable
logistic regression, with odds for recurrence of SFJ reflux recurrence at a mean of 6.6 years shown for relevant patient-related variables.
Variable OR (95% CIs)
BMI >29 at baseline (compared to <29) 1.65(1.12,2.43)
Prior parity (compared to none) 2.69(1.45,4.97)
Interim pregnancy (compared to not)* 4.74(2.47, 9.12)
*not a variable that can predict treatment efficacy at the pre-treatment stage, so excluded from results in review.
3
1 Table 27: Gibson et al. 2007103
Reference Study type No. of Patient characteristics Patient-related risk Outcome measures Length of Source of
patients factors studied prospective funding
follow-up /
retrospective
recollection
Gibson KD, Prospective n=187 C2-6 patients undergoing Anatomic patterns of the Incidence of the adverse 4-10 months None
Ferris BL, consecutive patients/210 EVLA SSV. Type A was a SPJ event of DVT at 2-4 days stated
Polissar N, enrolment of legs. High with no significant (but unclear)
Neradilek B, patients. Main (40%) attrition branches; type B was a
Pepper D. aim was to by the stage SPJ with a large extension Recanalisation at 2-11
Endovenous evaluate of the final Giacomini vein; type C months (but unclear)
laser treatment follow-up (2- was a SPJ or SFJ with no
treatment of success and 11 months). direct termination into a
the short modifiers of deep vein, and the SSV
saphenous AEs. continued as a Giacomini
vein: efficacy vein above the popliteal
123
and fossa. Author’s own

complications classification system.
. J Vasc Surg
2007; 45: Also: gender, leg side,
795-803 preoperative presence of
ulcer, pre-op presence of
stasis, pre-op presence of
pain, and age.
Results:
DVT risk factors
SSV anatomy had an association with DVT incidence. The risks of DVT for each group were as follows: Group A: 10/88 (11.4%); Group B: 2/69 (2.9%); Group C: 0/52
(0%). Specifically, a SPJ with no significant branches (Type A) carried a trend (p=0.07) for a higher risk than type B [type B compared to type A, for risk of DVT:
OR:0.23(0.05, 1.10)]. There were no DVT cases in type C, so no ORs could be produced, but the Fisher exact test showed that type C had a significantly lower risk than
type A (p=0.013).
No multivariable results are given, but this is because the only variable that had a p<0.1 on univariate testing was SSV anatomy type. Hence no variables other than SSV
Reference Study type No. of Patient characteristics Patient-related risk Outcome measures Length of Source of
patients factors studied prospective funding
follow-up /
retrospective
recollection
anatomy type would have been put in the multivariable model – hence the univariable results for SSV anatomy type are the full results. For completeness, all
univariable results are given below:
Risk factor for DVT (reference given in brackets) OR (95% CI) for DVT at variable time (adjusted for time)
right side (compared to left) 0.64(0.20, 2.09)
stasis (compared to no stasis) 0.46 (0.1, 2.16)
Age (per 10 year increment) 0.99(0.62,1.57)
Anatomy type B (compared to type A) [there were no 0.23(0.05, 1.10)
DVT cases in type C, so no ORs could be produced]
Gender 0/28 DVTs in men, 12/182 DVTs in women, p=0.4*
Pre-op ulcer 0/11 DVTs in those with ulcers, 12/199 DVTs in those with no ulcers, p=0.5*
124
Pain 0/13 DVTs in those with pain, 12/197 DVTs in those with no pain, p=0.5*
ulcer, stasis or pain 0/11 DVTs in those with ulcers, stasis or pain 12/199 DVTs in those with no ulcers, stasis or pain , p=0.5*
Recanalisation risk factors
A logistic regression analysis using the same risk factors was carried out to evaluate their effects on the odds of recanalisation. No results were reported, other than
that none of the variables had a significant relationship with recanalisation.
1
1 Table 28: Gonzalez-Zeh et al. 2008107
Reference Study type No. of Patient characteristics Patient-related risk Outcome Length of Source of
patients factors studied measures prospective funding
follow-up /
retrospective
recollection
Gonzalez- Non-randomised 98. No C2-6 patients undergoing EVLA Clinical grouping (C1- Presence of 1 week, 1 Not stated
Zeh R, trial with main aim patients and foam sclerotherapy. 6), pre-op VCSS, age, reflux, as month, 6
Armisen R, of comparing 2 dropped out Patients were allowed to pre-op GSV diameter measured by months and 1
Barahona S. treatments, but and all choose between foam duplex. year.
Endovenous with logistic followed up. sclerotherapy and EVLA, and
laser and regression analysis they were told the efficacy of
echo-guided included to assess each was equivalent.
foam effects of potential
ablation in treatment Inclusion: Primary
great modifiers. Only incompetence of the GSV and
saphenous one limb per SFJ insufficiency with a reflux
125
vein reflux: patient was time of 0.5 seconds measured

one year included and over a distance of at least 20cm
follow-up treated in this in the upper leg.
results. J Vasc study. A single
Exclusion: pregnancy; active
Surg 2008; surgeon with
thrombophlebitis, clotting
48: 940-6 experience of 800
disturbances; thrombophilia or
EVLA s and 2000
coagulation disorders; History
foam
of DVT; history of malignancies.
sclerotherapies did
both interventions. Baseline characteristics:
Patients were not Despite the lack of
allowed to mix, to randomisation the groups were
avoid well matched.
contamination of
patient
expectations.
Clinical and
Reference Study type No. of Patient characteristics Patient-related risk Outcome Length of Source of
patients factors studied measures prospective funding
follow-up /
retrospective
recollection
ultrasound follow-
ups done by an
assessor blinded to
treatment, but
probably not to
baseline
predictors.
Results:
Subgroups analysis showed that a larger pre-op GSV diameter was associated with reflux in both the foam and EVLA treatments. Veins <6.5cm have a 90% success rate
with foam, and veins <12mm have a 90% success rate with laser.
126
Logistic regression analysis showed that for each treatment, pre-op GSV diameter (?>12mm, unclear) was the only factor significantly predicting reflux. The
multivariable results for each treatment separately are given below. The OR(95% CIs) are for the odds of reflux. The analysis is unclearly reported. The reference values
for categorical variables (Clinical groups, GSV diameter) are unclear. It is likely that the reference value of GSV diameter is <12mm (therefore the variable below is given
as GSV >12mm). Though not stated it is likely that the ORs for the continuous variables (age, VCSS) are per increment increase in the variable.
Variable Foam sclerotherapy laser
clinical groups C1-6 0.89(0.39-2.20) 2.87(0.33-24.77)
VCSS 0.97(0.44-2.15) 0.31(0.03-3.12)
Age 0.99(0.91-1.08) 0.94(0.79-1.09)
GSV diameter (>12mm?) 1.68(1.24-2.27) 1.91(1.02-3.59)
1
2
1 Table 29: Islamoglu 2011122
Reference Study type No. of patients Patient characteristics Patient-related risk Outcome Length of Source of
factors studied measures prospective funding
follow-up /
retrospective
recollection
Islamoglu F. Prospective non- 372. No mention C2-6 patients Unilateral/bilateral, Symptom 6 months, and at Not stated
An randomised study. of drop-outs. undergoing foam pre-operative recurrence, post- further 6 month
alternative Patients were Unclear if the sclerotherapy with CEAP, employment, operative CEAP, intervals (mean
treatment for allowed to choose sample were crossectomy or classic familial post-operative follow-up was
varicose treatments. The defined by stripping. All done by the predisposition, Perforator 10.2 (5.1)
veins: ligation main aim was the completers only. same surgeon. Mean age gender, DVT, age, incompetence. months.
plus foam comparison of 48.6(10.1). 159/372 pre-operative deep
sclerotherapy stripping versus male. 156/372 in venous
. Dermatol foam sclerotherapy sclerotherapy group. All insufficiency (DVI),
surg 2011; and crossectomy, symptomatic. Bilateral in pre-operative
37: 470-479 but in the absence 51 subjects. perforator
127
of a differential incompetence (PI).

treatment effect Inclusion: GSV reflux;
most of the results C2-6; primary aetiology.
sections focus on
Exclusion: pregnancy;
the non-treatment
sclerosant allergy; acute
predictors of
thrombophlebitis; acute
treatment
DVT; local infection;
success/failure.
immobility.
Results
Multivariable results only, all adjusted for treatment type (always NS in all analyses) as well as other variables. The time of follow-up is unclear, but presumably 6-12
months.
Post-op symptom recurrence
These results were poorly reported by the paper. The directions of the ORs in the text do not tally with the raw data for the unilateral/bilateral variable. The direction
of effect given below is that determined by the raw data. ORs are for the existence of post-operative symptom recurrence.
unilateral (versus bilateral) 2.376 (1.682-3.356)
Reference Study type No. of patients Patient characteristics Patient-related risk Outcome Length of Source of
factors studied measures prospective funding
follow-up /
retrospective
recollection
Pre-op CEAP >3 (versus <3) 3.298(1.897-5.731)
No job (versus a job) 0.133(0.073-0.243)
No family history (versus a family 0.357(0.198-0.643)
history)
Post-op CEAP < 3
Again, poorly reported. ORs are for post op CEAP <3
unilateral (versus bilateral) 2.497(1.337-4.663)
Pre-op CEAP <3 (versus >3) 1.445(0.368-4.818)
male (versus female) 1.542(0.201-3.355)
128
No previous DVT (versus 2.827(0.831-9.619)

previous DVT)
Age <60 (versus >60) 1.215(0.262-4.012)
Post-op perforator incompetence
Age >60 (compared to <60) 23.618(8.423-66.223)
Pre-op CEAP >3 (compared to 2.741(1.174-6.401)
<3)
No job (compared to employed) 0.112(0.039-0.317)
Family history (compared to 2.927(1.020-8.398)
none)
Pre-op PI (compared to none) 6.102(2.214-16.815)
There was also a multivariable analysis evaluating which factors were associated with earlier (<1 year) or later symptom recurrence, amongst the sub-group with
symptom recurrence. Results of this have not been included in this review because they are outside the scope of the review question.
1
1 Table 30: McKenzie et al. 2002156
Reference Study type No. of patients Patient characteristics Patient-related risk factors Outcome Length of Source of
studied measures prospective funding
follow-up /
retrospective
recollection
McKenzie RK, Lee Prospective study of 203. No mention of C2-6 patients age, gender, pre-operative AVVSSS Post-operative 6 months/ 2 yearsNone stated.
AJ, Paisley A et al. consecutive drop-outs. Unclear if undergoing GSV, SSV or (high = worse), CEAP grade, first AVVQ
Patient, operative, unselected patients, the sample were SEPS surgery. GSV time/recurrent, History of DVT. In
and surgeon aiming to look for defined by surgery comprised flush patients with bilateral disease, the
factors that factors influencing completers only. SPJ ligation, stripping of factors entered into the analysis
influence the effectdisease-specific the GSV in the thigh andwere those for the worst affected
of superficial quality of life. This multiple stab avulsions; leg.
venous surgery on included patient SSV surgery comprised
disease-specific factors, as well as SPJ ligation and multiple
quality of life. J operative and stab avulsions; SEPs was
vasc Surg 2002; 36:surgeon factors. done with a single port
129
896-902 technique.
Results:
6 months multivariable
A higher baseline AVVQ, baseline recurrent disease and baseline CEAP 4 disease predicted higher (worse) AVVQ at 6 months. This model explained 60% of the total
variation in AVVQ at 6 months. Square root used to normalise the distribution of baseline AVVQ (Log not possible as raw scores included zero)
Factor Parameter estimate SE t p
square root of baseline AVVQ 0.57 0.07 7.78 <0.001
primary/recurrent procedure 0.45 0.17 0.15 0.009
CEAP 4 0.39 0.17 0.14 0.026
2 years multivariable
A higher baseline AVVSS and baseline CEAP 5 disease predicted higher (worse) AVVQ at 2 year. In contrast, previous GSV surgery predicted a lower AVVQ. This model
explained 47% of the total variation in AVVQ at 2 years. Square root used to normalise the distribution of baseline AVVQ (Log not possible as raw scores included zero)
Factor Parameter estimate SE t p
square root of baseline AVVQ 0.47 0.08 6.16 <0.001
Reference Study type No. of patients Patient characteristics Patient-related risk factors Outcome Length of Source of
studied measures prospective funding
follow-up /
retrospective
recollection
GSV surgery -0.73 0.31 -2.35 0.02
CEAP 5 0.62 0.28 2.19 0.030
1
130
1 Table 31: Myers 2007180
Myers KA, Prospective 489 patients Inclusion: C2-6 patients Type of vein, age, gender, Time to failure was the Every 3-5 days Not stated
Jolley D, observational (677 limbs). undergoing ultrasound diameter of GSV, side, outcome. Treatment after each of the
Clough A, study. Main Time to guided sclerotherapy CEAP grade. success defined as 1-4 sclerotherapy
Kirwan J. aim was to event study (mainly foam but some persistent occlusion or sessions; then at
Outcome of evaluate so attrition liquid). Some of these absence of reflux in 6 weeks; and
ultrasound- modifiers of catered for in were given over 3-4 treated veins – assessed then at 6 months
guided treatment analysis. separate sessions. by ultrasound (unclear if for 2 years; and
sclerotherapy success. duplex). Time to failure then annually.
for varicose Exclusion: Previous EVLA was therefore the
veins: duration between the
medium-term first treatment session
Age range 19-92 (median
results (out of the 1-4)
53); women: 401/489;
assessed by achieving full success
C2-3 in 90%; 115 limbs
ultrasound and the first follow-up
were recurrent and the
131
surveillance. when reflux was noted.

rest were first-time.
Eur J Vasc
Endovasc
Surg 2007;
33: 116-121
Results: A multivariable cox-regression analysis was carried out for factors influencing failure in all saphenous veins. The table below summarises the results, with a
higher HR indicating a greater risk of failure at any point in time compared to the reference category. Younger age and larger (>6mm) diameter GSV were associated
with a worse outcome.
Variable (and reference Index category of n Hazard Ratio (95% CI)

category) variable
Age (compared to 50-59) <40 93 2.16(1.27,3.66)
40-49 121 1.11(0.69,1.78)
60-69 118 1.22(0.79,1.89)
70+ 87 0.63(0.35,1.14)
Sex (compared to female) Male 112 1.31(0.88,1.94)

Side (compared to left) Right 313 1.19 (0.89, 1.57)
Vein (compared to GSV) SSV 174 1.58(1.11, 2.24)
CEAP (compared to C2/3) C4/6 62 1.57(0.91, 2.73)
vein diameter (compared to 5 mm 152 1.27((0.79,2.03)
<5mm) 6mm 152 2.07(1.35, 3.18)
>6mm 112 2.22(1.4, 3.5)
1
132
1 Table 32: Thomasset 2010268
Reference Study No of patients Patient Risk factors studied Outcome measures Length of Source of
type characteristics follow-up funding
Thomasset Prospec 116 patients, having 126 procedures. 53 men, 63 Gender Successful outcome 3 months None.
SC, Butt Z, tive women. Median – complete occlusion minimum
Liptrot S, cohort Appears to have very high attrition, as age was 55 (range Previous surgery of the target vein on
Fairbrother study. only 116/235 eligible patients 18-80). Target duplex analysis on
attended follow-up. These could have Sites of injection
BJ, veins were the follow-up.
Makhdoomi included the worst (or best) GSV (n=75), SSV Maximum
KR. responders. But how many of these (n=13), and Existence of any
concentration of
Ultrasound eligible patients were actually accessory GSV complications
sclerosant
guided foam recruited in the first place? Very (n=8). Others
unclear. Existence of each
sclerotherapy involved other Pre-procedure CEAP
complication
: factors veins or more
Unclear if analysis was by procedure Compliance with analysed separately
associated than a single
(n=126) or patient (n=116), but likely post treatment (superficial
with target vein
to be the latter, as there would compression thrombophlebitis,
outcomes (n=30).
133
probably only have been one outcome pain, skin staining,

and
assessment per person, and thus one Age DVT, allergy and skin
complications
analysis (for example if a patient had blistering)
. Eur J Vasc Volume of sclerosant
two UGFS procedures, the second
Endovasc
would be a top up and a single
Surg 2010;
outcome would relate to both).
40: 389-392
Results: Analysis was poorly reported though it seems univariate analyses for the 8 risk factors were performed. Although this study did therefore not meet the
inclusion criterion of having a multivariable analysis, because only one risk factor was significant on univariate testing, a multivariable analysis would have been an
unnecessary next step anyway, so this study has been included.
For the outcome of complete occlusion of the target vein, the only risk factor associated was compliance with post-procedure compression hosiery (p<0.05). No effect
sizes were presented. This is not a factor that could be ascertained pre-treatment (although it is conceivable that patients could be asked if they thought they’d be
compliant with stockings after treatment) and so has little value in making a pre-treatment prediction about which patients will do well.
For the outcome of any complication, female gender was associated with a greater risk (p<0.05). No effect size was reported. For each complication considered
separately, female gender was associated with skin staining (P<0.05). No effect sizes were given. There were no associations between female gender and any other
complications considered singly.
2
G.3 Chapter 7 – assessment for treatment
2 G.3.1 Diagnostic accuracy of hand held Doppler ultrasound
3 Table 33: Campbell 199744
Reference Study No of Patient Intervention Comparison Other issues of Outcome Source of

type patients characteristics importance measures funding
Campbell WB, Diagnosti 85 (122 legs) Patients referred to Hand held doppler. Duplex, using a Blinding NOT stated Sensitivity Not
Niblett PG, Ridler c review the vascular Performed in Diasonics VST and reported
BMF, Peters AS, study. outpatient clinic standing. Tourniquet masters scanner Test interval not specificity
Thomson JF. Hand with primary and test used for the with a 5MHz clear: “another
held doppler as a previously un- GSV. Positioning not linear array visit”.
screening test in operated varicose given. >1 second probe.
Expertise
primary varicose veins. reflux regarded as Positioning not
comparability not
veins. British significant. Carried given. >1 second
Gender: 52 women clear.
134
Journal of Surgery out by reflux regarded

1997; 84: 1541- consultant(103 legs), as significant. No previous
Age:range18-89
1543 trainee (in 17) and Duplex operator treatments. CEAP
(median 53).
unknown (2 legs). not reported. status not reported.
Results: Raw data only available for the popliteal fossa (percentages given for the GSV, but not possible to convert these to raw numbers due to lack of data on the
numbers with duplex-confirmed reflux).
popliteal fossa +ve on -ve on
duplex duplex
+ve onHHD 28 8
-ve on HHD 11 74
Popliteal fossa +ve and –ve predictive values, and all CIs, derived from raw data. No raw data given for groin or 10cm below groin.
Site examined sensitivity Specificity Positive predictive value Negative predictive value
Great Saphenous Vein 0.86 0.82 - -
10cm below groin (alternative GSV) 0.81 0.85 - -
Popliteal fossa 0.72 (0.55-0.85) 0.90(0.82-0.96) 0.78(0.62-0.88) 0.87(0.78-0.93)
1 Table 34: Darke 199764
Reference Study type No of Patient Intervention Comparison Other issues of Outcome Source of
patients characteristics importance measures funding
Darke SG, Diagnostic 73 73 patients referred continuous wave Duplex, using an Blinding carried out Sensitivity Not stated
Vetrivel S, Foy accuracy patients to a consultant Doppler, using a Acuson 128/10 and
DMA, Smith S, study (100 legs) vascular surgeon Huntleigh dopplex colour duplex Test interval not specificity
Baker S. A with primary 500 probe at 8MHz. scanner with a stated
comparison of uncomplicated Positioning not 7MHz linear array
Expertise
duplex varicose veins. given. Reflux probe. This was
comparability not
scanning and definition not carried out blind to
Gender: 55 females; clear.
continuous described in terms the doppler
wave doppler Age: mean 47.5 of duration. findings. Reflux Stage of disease and
in the (range 22-74); defined as >0.5 previous treatment
assessment of Carried out by a secs. Carried out by history not given.
primary and “single observer”. a medical
uncomplicated technologist.
varicose veins.
135
Eur J Vasc
Endovasc Surg
1997; 14: 457-
461
Results: No CIs provided in the paper. The raw data below were gathered from the paper, and the CIs were calculated.
Great +ve on -ve on Short saphenous +ve on duplex -ve on duplex

saphenous duplex duplex vein
vein
+ve on HHD 83 0 +ve on HHD 19 5
-ve on HHD 4 13 -ve on HHD 2 74
In paper only sensitivity and specificity provided, but +ve and –ve predictive values have been calculated from the raw values.
Site examined sensitivity [TP/TP+FN] Specificity [TN/TN+FP] +ve predictive value [TP/TP+FP] -ve predictive value
[TN/TN+FN]
Reference Study type No of Patient Intervention Comparison Other issues of Outcome Source of
Great [83/83+4] [13/13+0]. [83/83+0] [13/13+4].
saphenous vein 0.95(0.89-0.99) 1.00(0.75-1.00) 1.00(0.95-1.00)) 0.75(0.52-0.89)
Short [19/19+2] [74/74+5] [19/19+5] [74/74+2]
saphenous vein 0.90(0.70-0.99) 0.94(0.86-0.98) 0.79(0.59-0.91) 0.97(0.91-0.99)
1
136
1 Table 35: DePalma 199376
Reference Study type No. of patients Patient Intervention Comparison Other issues of Outcome Source of
characteristics importance measures funding
DePalma RG, Diagnostic 40 (80 legs) Symptomatic Hand held 9.1 Duplex, with a Blinding carried Sensitivity and Not reported
Hart MT, Zanin review study. patients MHz CW QUAD-1 colour out specificity,
L and Massarin presenting with Doppler pencil flow scanner, positive
EH. Physical primary probe at an with 5MHz Test interval predictive
examination, varicosities in acute angle of probe. Carried not stated value, negative
doppler the great 30-45 deg. out in standing predictive value
Expertise
ultrasound and saphenous Patient and supine. No
comparability
colour flow distribution. positioning not definition of
not clear.
duplex described. No reflux duration
scanning: Gender: 31 definition of threshold. 28% with prior
guides to women; reflux duration Carried out by stripping. CEAP
therapy for Age: 27-64 yrs; threshold. 2 vascular status not
primary Carried out by technical reported
All had mild-
varicose veins. senior author, observers.
137
moderate
Phlebology who was
symptoms.
1993; 8: 7-11. probably a
Typical
vascular
symptoms were
surgeon, but
aching in the
unclear.
evening. 22/80
limbs had had
prior stripping,
but were still
symptomatic.
Results: Raw data
SFJ +ve on duplex -ve on duplex SFJ in sub-group with previous +ve on duplex -ve on duplex
stripping n=22
+ve onHHD 24 5 +ve onHHD 8 1
No CIs given in paper. CIs calculated from raw values.
Site examined sensitivity [TP/TP+FN] Specificity [TN/TN+FP] Positive predictive value Negative predictive value
[TP/TP+FP] [TN/TN+FN]
SFJ n=80 limbs [24/24+26] 0.48(0.34-0.63) [25/25+5] 0.83(0.65-0.94) [24/24+5] 0.83(0.66-0.92) [25/25+26] 0.49(0.36-0.62)
SFJ in sub-group [8/8+9] 0.47(0.26-0.69) [4/4+1] 0.80(0.38-0.96) [8/8+1] 0.89(0.57-0.98) [4/4+9] 0.31(0.13-0.58)
with previous
stripping n=22
1
2
138
1 Table 36: Kent 1998131
Reference Study type No. of Patient characteristics Intervention Comparison Other issues Outcome Source of
patients of importance measures funding
Kent PJ, Weston Diagnostic 72 People with primary Hand held Doppler, Duplex (with Blinding Sensitivity, None stated
MJ. Duplex accuracy patients varicose veins, who had with 8MHz probe guided pulse wave carried out specificity.
scanning may study. (108 not undergone previous (Multi-Duplex). spectral doppler), Positive
be used limbs) injection sclerotherapy or Carried out by one using a Siemens Tests predictive
selectively in surgical treatment. consultant Q2000 machine, followed each value and
patients with Gender: 20 males and 52 vascular surgeon. with a 5 MHz other negative
primary females. Measurement curvilinear probe. immediately predictive
varicose veins. Median age: 44.5 years performed in the Patient measured value of hand
Expertise of
Ann R Coll Surg (range 19-73 years). standing position, in standing with held Doppler.
operators
Engl 1998;80: with the affected weight off the
CEAP stage (limbs): comparable
388-393 limb slightly flexed affected limb.
C1: 1/108 at hip and knee. Reversed flow of No previous
C2: 96/108 The probe placed over 1 second was treatment
C3: 0/108 over the sapheno- considered
139
and mostly
C4: 9/108 femoral junction abnormal. Carried CEAP stage 2
C5; 0/108 and the calf out immediately
C6: 2/108 compressed. after hand held
Reflux lasting Doppler scanning.
longer than 0.5 This was carried
seconds was out by another
regarded as consultant
significant. This radiologist who
was then repeated was unaware of
at the great the results of the
saphenous vein. HHD assessment
Results: HHD diagnostic accuracy compared to gold standard of Duplex. This study did not report the raw data. The data below is all that was presented.
(* with tourniquet)
Site examined sensitivity specificity Positive predictive negative predictive
value value
SFJ 0.93 0.91 0.96 0.86
GSV 0.95 0.68 0.91 0.81
MTP* 0.87 0.26 0.16 0.92
SPJ 0.82 0.80 0.44 0.96
PV* 0.50 0.90 0.44 0.92
1
2
140
1 Table 37: Kim 2000134
Reference Study type No. of Patient Intervention Comparison Other issues of Outcome Source of
Kim J, Richards Diagnostic 44 Primary and Hand held Doppler Duplex (with guided Blinding Sensitivity, None stated
S, Kent PJ. accuracy patients previously with 8MHz probe pulse wave spectral carried out specificity.
Clinical study. (70 untreated (Huntleigh doppler), using a Positive
examination of limbs) varicose veins technologies). Diagnostic US Tests followed predictive value
varicose veins – presenting for Patient stood on systems 3535 each other and negative
a validation Duplex scanning unaffected leg. machine (B&K immediately predictive value
study. Ann were tested. Probe placed on Medical, Denmark) of hand held
Expertise of
Royal College Secondary sapheno-femoral machine, with a 5 Doppler
operators not
Surgery Engl varicose veins junction. Calf MHz curvilinear
comparable.
2000; 82: 171- and previous squeezed, and probe. Reversed
175. surgery patients subsequent reflux of flow of over 1 No previous
excluded. <0.5 sec was second was treatment and
deemed significant. considered mostly C2
CEAP stages: Then repeated over abnormal. Carried
141
C1: 2/70, the GSV and SPJ. out immediately

C2: 67/70 Carried out by after hand held
C3: 1/70. house officer Doppler scanning.
This was carried out
by a vascular
technologist who
was unaware of the
results of the hand
held Doppler
assessment
Results: This study did not report the raw data. The data below is all that was presented
Site examined sensitivity specificity Positive predictive value Negative predictive value
SFJ 0.97 0.73 0.80 0.96
GSV 0.82 0.92 0.84 0.74
SPJ 0.80 0.90 0.57 0.97
2
1 Table 38: Mercer 1998167
Reference Study No. of Patient Intervention Comparison Other issues of Outcome Source of
Mercer KG, Diagnostic 61 Primary varicose Hand held doppler, At a separate Blinding definitely Sensitivity, Not
Scott DJA, accuracy patients veins. with 8MHz probe appointment (time NOT carried out specificity reported
Berridge DC. study. (81 legs) (Multi-Dopplex). after not described) (duplex operator of hand
Pre-operative Carried out by one Colour flow duplex reported as having held
duplex imaging consultant vascular using a Siemens access to hand held Doppler
is required surgeon. In standing Quantum 2000 or B&K Doppler results)
before all with the affected leg 3535 (with Acuson 128
operations for slightly flexed, reflux 5MHz curvilinear Test interval unclear,
primary looked for at sapheno- probe). Positioning but described as at a
varicose veins. femoral junction, great unclear. Carried out by separate
British journal saphenous vein and a consultant vascular appointment
of Surgery sapheno-popliteal radiologist. Reflux
Expertise of operators
142
1998; 85: junction. Reflux >0.5 >0.5 sec regarded as

comparable.
1495-1497. sec regarded as significant.
significant. Treatment history
and stage of disease
unclear
Results: Raw results:

SFJ +ve on -ve on SPJ +ve on duplex -ve on
duplex duplex duplex
Thigh +ve on -ve on

Perforators duplex duplex
+ve onHHD 18 8
-ve on HHD 17 46
Positive and negative predictive values not given in paper, but calculated from raw values.
Site examined sensitivity [TP/TP+FN] Specificity [TN/TN+FP] Positive predictive value [TP/TP+FP] Negative predictive
value [TN/TN+FN]
SFJ [43/43+16] [28/28+2] [43/43+2] [28/28+16]
0.73 (0.60-0.84) 0.93 (0.78-0.99) 0.96 (0.85-0.99) 0.64 (0.50-0.76)
SPJ [20/20+6] [59/59+4] [20/20+4] [59/59+6]
0.77 (0.56-0.91) 0.94 (0.85-0.98) 0.83 (0.64-0.93) 0.91 (0.81-0.96)
Thigh [18/18+17] [46/46+8] [18/18+8] [46/46+17]
perforator 0.51 (0.34-0.69) 0.85 (0.73-0.93) 0.69 (0.5-0.84) 0.73 (0.61-0.82)
1
2
143
1 Table 39: Rautio 2002B226
Rautio T, Perala Diagnostic 49 patients Patients with Hand held Doppler Duplex scanning Blinding Sensitivity, None stated
J, Eiik H, accuracy (62 legs). primary, with an 8MHz with a 5MHz carried out specificity.
Haukipuro K, study. previously probe (Hadeco probe (Toshiba Positive
Juvonen T. untreated and minidoppler ES- Power Vision Tests followed predictive value
Influence of uncomplicated 100X). Patients 8000, Japan). each other at and negative
preoperative varicose veins, tested in a semi- Patients supine same predictive value
duplex referred for supine position. with slight truncal appointment of hand held
ultrasonograph surgery. The sapheno- elevation. Reverse Doppler.
Expertise of
y on the femoral junction, flow of >1 second
Exclusion: operators
operative and the great regarded as
previous history of comparable.
procedure for saphenous vein at pathological.
primary DVT. three separate Done by a No previous
varicose vein points, were consultant treatment and
Median age: 45.5
surgery. insonated. An vascular
144
years (range 19- venous

Phlebology audible flow radiologist blinded disability score
66).
2002; 16: 149- signal lasting for > to the hand held of 0-1
Gender: 5 male
153 1 sec was Doppler results.
and 44 female
significant. The
patients.
Sapheno-popliteal
Venous disability junction and short
score was 0-1 in all saphenous vein
cases. Superficial were also
reflux was insonated if there
detected in 55/62 were clinical
limbs. No deep evidence
vein/perforator suggesting
reflux detected. involvement.
Done by an
experienced
General Surgeon.
Results: Raw data:

SFJ +ve on -ve on GSV1 (mid thigh) +ve on duplex -ve on duplex
duplex duplex [these findings
were used for the
report]
GSV2 (popliteal +ve on -ve on GSV3 (calf) +ve on duplex -ve on duplex
fossa) duplex duplex
95% CIs are also included in round brackets. Raw data in italics and square brackets.
145
Site examined sensitivity [TP/TP+FN] Specificity [TN/TN+FP] +ve predictive value [TP/TP+FP] -ve predictive value [TN/TN+FN]
[31/31+17] [13/13+1] [31/31+1] [13/13+17]
SFJ
0.65 (0.49-0.78) 0.93 (0.66-1.00) 0.97 (0.84-0.99) 0.45 (0.29-0.62)
[24/24+25] [12/12+1] [24/24+1] [12/12+25]
GSV1 (mid
thigh) 0.49 (0.34-0.64) 0.92 (0.64-1) 0.96 (0.81-0.99) 0.32 (0.20-0.49)
[22/22+19] [18/18+3] [22/22+3] [18/18+19]
GSV2 (popliteal
fossa) 0.54 (0.39-0.68) 0.86 (0.65-0.95) 0.88 (0.70-0.96) 0.47 (0.33-0.64)
[15/15+17] [27/27+3] [15/15+3] [27/27+17]
GSV3 (calf)
0.47 (0.30-0.64) 0.90 (0.74-0.97) 0.83 (0.61-0.94) 0.61 (0.47-0.74)
1
1 Table 40: Rautio 2002A225
Rautio T, Diagnostic 111 Patients referred for Hand held Duplex scanning Blinding Sensitivity and Not
Perala J, review study. patients surgical treatment of doppler using a with a 7.5MHz carried out specificity, reported.
Biancari F, (142 varicose veins with primary, 8MHz probe probe (Toshiba positive
Wiik H, Handheld limbs) uncomplicated and (Hadeco mini- Power Vision Test interval predictive
Ohtonen P, Doppler and previously untreated doppler ES- 8000). within the value, negative
Haukipuro K, Duplex done on varicose veins 100X). Patients Positioning as for same day predictive
Juvonen T. the same day by were examined the hand held value and
different Exclusion: History of lower Expertise of
Accuracy of in a semi-supine Doppler kappa co-
people. limb venous thrombosis operators
hand held position with the examination. efficient.
comparable
doppler in upper body Reflux >1 second
Gender: 96 females
planning the elevated at 45 was regarded as Mostly C2-3,
Mean age (range): 42(23-
operation for degrees. Audible significant. and had no
76)
primary flow signal of >1 Carried out by previous
mean BMI (range):
varicose veins. sec was taken as consultant
146
25.6(18.3-52.8); treatments.
Eur J Vasc the threshold of vascular
Endovasc Surg Venous disability score significant radiologist.
2002; 24: 450- 0: 14/111, reflux. Carried
455 1: 85/111, out by
2: 12/111; consultant
general surgeon.
CEAP stage:
C1 (5/142),
C2 (67/142),
C3 (59/142),
C4 (11/142).
Results:
-ve on duplex
SFJ +ve on duplex GSV1 (upper +ve on duplex -ve on duplex
thigh)
-ve on duplex
GSV2 (lower +ve on duplex GSV3 (calf) +ve on duplex -ve on duplex
thigh)
-ve on duplex
SPJ +ve on duplex
+ve onHHD 3 4
-ve on HHD 10 95
95% CIs are also included in round brackets. Raw data in italics and square brackets.
Site examined sensitivity Specificity [TN/TN+FP] +ve predictive value [TP/TP+FP] -ve predictive value [TN/TN+FN] kappa co-
147
[TP/TP+FN] efficient
SFJ n=142 [59/59+46] [36/36+1] 0.97(0.86-100) [59/59+1] 0.98(0.91-1) [36/36+46] 0.44(0.34-0 38(24-53)
0.56(0.46-0.66) .55)
GSV1 (upper [54/54+39] [41/41+8] 0.84(0.70-0.93) [54/54+8]0.87(0.77-0.93) [41/41+39] 0.51(0.41-0.62) 36(21-51)
thigh) n=142 0.58(0.47-0.68)
GSV2 (lower [53/53+33] [59/59+10] 0.82(0.70- [53/53+10]0.84(0.73-0.91) [59/59+33] 0.58(0.47-0.69) 41(26-56)
thigh) n=142 0.62(0.51-0.71) 0.90)
GSV3 (calf) [46/46+23] [59/59+14] 0.81(0.70- [46/46+14]0.77(0.65-0.86) [59/59+23] 0.72(0.61-0.81) 48(33-62)
n=142 0.67(0.55-0.77) 0.88)
SPJ n=112 [3/3+10] [95/95+4] 0.96(0.90-0.99) [3/3+4]0.43(0.16-0.75) [95/95+10] 0.91(0.83-0.95) 24(-14–61)
0.23(0.05-0.54)
1
1 Table 41: Salaman 1995236
Salaman RA,
Diagnostic 42(72) Patients Hand held Duplex done Blinding Sensitivity and Not stated
Fligelstone LJ,
accuracy study awaiting Doppler with a with a Toshiba unclear – specificity,
Wright N, Pugh
varicose vein Dopplex MD2 SPA270A reported that Positive
KG, Harding KG,
surgery or bi-directional scanner with a “both predictive
Lane IF. Hand
attending the hand-held 5MHz linear investigations value, Negative
held bi-
vascular Doppler unit array probe. were reported predictive value
directional
outpatient clinic with an 8MHz Done by a independently”
doppler versus
with probe. Reflux vascular
colour duplex Test interval
symptomatic duration medical
scanning in the not reported.
varicose veins. threshold not scientist. Reflux
pre-operative
stated. Done by defined as >0.5
assessment of Expertise of
an experienced secs of
varicose veins. J operators
vascular retrograde
Vasc Invest probable.
research flow.
148
1995; 1:183-6
fellow. Surgical history
unclear and
disease severity
unclear.
Results: NB: these data are extracted from data provided, in a different form, in the paper. Note how the total n in each grid varies, from 72 (the expected value) to 77.
This must be due to errors in the data on the paper.
SFJ +ve on duplex -ve on duplex SPJ +ve on duplex -ve on duplex
Thigh +ve on duplex -ve on duplex calf/ankle +ve on duplex -ve on duplex
perforator perforator
common +ve on duplex -ve on duplex popliteal +ve on duplex -ve on duplex
femoral
Site examined sensitivity [TP/TP+FN] specificity Positive predictive value Negative predictive value
[TN/TN+FP] [TP/TP+FP] [TN/TN+FN]
SFJ [49/49+4] 0.92(0.82-0.98) [18/18+1] 0.95(0.74-1.00) [49/49+1] 0.98(0.90-0.99) [18/18+4] 0.82(0.62-0.93)
SPJ [10/10+8] 0.56(0.31-0.78) [50/50+6]0.89(0.78-0.96) [10/10+6] 0.63(0.39-0.82) [50/50+8] 0.86(0.75-0.93)
Thigh [2/2+5] 0.29(0.04-0.71) [54/54+13] 0.81(0.69-0.89) [2/2+13] 0.13(0.04-0.38) [54/54+5] 0.92(0.82-0.96)
perforators
149
Calf/ankle [2/2+4] 0.33(0.10-0.70) [67/67+4] 0.94(0.86-0.98) [2/2+4] 0.33(0.10-0.70) [67/67+4] 0.94(0.86-0.98)

perforators
Popliteal [2/2+3] 0.4(0.05-0.85) [68/68+1] 0.99(0.92-1) [2/2+1] 0.67(0.21-0.94) [68/68+3]0.96(0.88-0.99)
1
1 Table 42: Schultheiss 1997241
Reference Study type No. of Patient Intervention Comparison Other issues Outcome Source of
patients characteristics of importance measures funding
Schultheiss R, Diagnostic 19 patients Patients with chronic Hand held cw doppler Duplex carried out by Blinding Sensitivity, Swiss
Billeter M, accuracy (19 limbs) venous insufficiency. ultrasound carried another medical carried out specificity of Phlebology
Bollinger A, study. 2 described as C3, 14 out by experienced doctor blinded to hand held Society.
Franzeck UK. as C4 and 3 as C5. medical doctor. 8.2 or HHD results. Linear 5 Test interval Doppler.
Comparison 5.3 MHz pencil probe and 7 MHz probes not stated
between clinical Exclusion: C6 disease, (Parks Electronics Lab were used (Acuson
PAD, cardiac Expertise
examination, model 10110). Testing 128 XP/10). Done in
problems, diabetes comparability
cw-Doppler carried out in standing. Reflux
mellitus, not clear.
Ultrasound and standing over areas of defined as reverse
Colour-duplex nephropathy. marked fascial defect. flow of >0.5 sec.
sonography in No definition of
Age: Mean age of the
the diagnosis of reflux given in terms Mostly C4.
women was 62.8
incompetent of duration. Previous
years (range 44-79
perforating treatment
150
years) and of the men

veins. Eur J vasc status not
was 56.3 years (range
Endovasc surg given.
32-76).
1997; 13: 122-
126.
RESULTS: Usable raw data was not presented. Only the results below were mentioned in the discussion
Site examined sensitivity specificity
perforating veins 0.29 0.15

2
1 Table 43: van der Heijden 1993276
van der Heijden Diagnostic 48 (68 legs) Patients with Continuous Duplex carried Blinding carried No diagnostic None stated
FHWM, study leg varicose wave doppler out by a surgical out outcomes
Bruyninckx veins. done by a resident. presented by
CMA. vascular Toshiba SSA- Test interval the paper, but
Preoperative Gender: 35 technician. No 270A machine not stated, but some raw data
colour-coded women; other details used, with appears to be allowed
duplex scanning Age: mean age given of 5MHz linear same day calculations.
in varicose 48 years (range positioning or array
16-77); Expertise
veins of the definition of transducer.
Previous comparability
lower reflux in terms Patients
treatment: 10 probable.
extremity. Eur J of duration. examined
Surg 1993; 159: had had upright. Reflux 21% with prior
329-333 previous of 0.5 seconds stripping. CEAP
stripping. regarded as
151
status not
significant. reported
Results: These were based on interpretation of the data in the paper which was presented (the numbers with duplex signs of incompetence were given, and also
specific information given where there was discordance between HHD and duplex). In some cases a false negative result was not due to failure to observe reflux, but
an incorrect identification of the source of reflux. Accuracy of these data is suspect.
SFJ +ve on duplex -ve on duplex Great +ve on duplex -ve on duplex
saphenous vein
short +ve on duplex -ve on duplex Perforating +ve on duplex -ve on duplex
saphenous vein veins
+ve on HHD 16 0 +ve on HHD 10 1
SPJ +ve on duplex -ve on duplex
+ve on HHD 17 0
-ve on HHD 0 51
Site examined sensitivity [TP/TP+FN] Specificity [TN/TN+FP] Positive predictive value Negative predictive value
[TP/TP+FP] [TN/TN+FN]
SFJ [45/45+2] 0.96(0.85-0.99) [20/20+1] 0.95(0.76-1) [45/45+1] 0.98(0.89-0.99) [20/20+2] 0.91(0.72-0.98)
Great [41/41+4] [22/22+1] [41/41+1] [22/22+4]
saphenous vein 0.91(0.79-0.98) 0.96(0.78-1) 0.98(0.88-0.99) 0.84(0.67-0.94)
Short [16/16+2] [50/50+0] [16/16+0] [50/50+2]
saphenous vein 0.89(0.65-0.99) 1(0.93-1) 1(0.77-1) 0.95(0.86-0.99)
Perforating [10/10+9] [17/17+1] [10/10+1] [17/17+9]
veins 0.53(0.29-0.76) 0.94(0.73-1) 0.91(0.62-0.98) 0.65(0.46-0.81)
152
SPJ [17/17+0] 1(0.8-199) [51/51+0] 1(0.93-1) [17/17+0] 1(0.78-1) [51/51+0] 1(0.91-1)
1
2
1 Table 44: Wills 1998284
Wills V, Diagnosti 188 Patients with Hand held doppler Duplex, using a Blinding NOT stated. Sensitivity None
Moylan D, c accuracy patients varicose veins who combined with Toshiba 270 scanner and reported
Chambers J. study (315 had been referred to clinical assessment. with a 5 MHz probe Time interval not specificity
The use of legs) a vascular surgeon. Parks hand-held and colour flow stated. Delay likely as
routine duplex doppler probe imaging. Leg being stated that patient were
scanning in (8MHz) used. This examined was in a ‘referred’ for duplex.
the Gender: 142 female was combined with dependent position.
Mean age 54.1 yrs Expertise of operators
assessment of clinical assessment, Reflux defined as
(range 21-79 years) probably comparable.
varicose veins. involving retrograde flow of
Aust NZ J Surg Previous trendelenburg >1 sec after the 39% had had previous
1998; 68: 41- treatment:122/315 testing with a release of manual treatment and 31% had
44 legs tourniquet. Patient calf compression. skin changes
Of these, 86 legs had position not Done by a trained
had high ligation + described. Reflux vascular technician.
153
other treatment, 8 definition not

had stab avulsions described in terms of
and 29 had duration. Done by a
sclerotherapy. specialist vascular
surgeon.
16/315 legs were
thought to have
secondary varicose
veins (15 previous
DVT and 1
arteriovenous
malformation);
skin changes present
in 99/315 legs
C4: 69
C6: 30
No disease, or only
superficial
tributaries, with a
normal great
saphenous vein, was
seen in 35 legs.
Results: Insufficient raw data given. The data below is all that was given in the paper.
Site examined Sensitivity Specificity

Sapheno-femoral junction 71.2% 70.9%
Sapheno-popliteal junction 36.1% 92.1%
Perforating veins 43.6% 78.7%
Deep Venous 29.2% 94.8%
SFJ of a sub-group of legs with 80.2% 52.2%
154
‘uncomplicated’ varicose veins (no skin

changes and not recurrent)
1
1 G.3.2 Duplex assessment prior to interventional treatment
2 Table 45: Blomgren 2006A25
Reference Study type No. of Patient characteristics Intervention Comparison Length of Outcome Source of
patients follow-up measures funding
Blomgren L, RCT. Sealed 293 Inclusion: Primary varicose veins. Pre-operative No pre- 2 years Quality of None
Johansson G, envelope randomised Duplex scan. operative life
Bergqvist D. system used (though Exclusion: pure cosmetic complaints, duplex scan.
Quality of life for unclear). 237 previous venous surgery or Surgical Patient
after surgery for allocation reported to sclerotherapy, history of suspected procedures Surgical assessed
varicose veins concealmen have given full or manifest deep venous thrombosis, that followed procedures symptoms
and the impact of t. follow-up active or healed leg ulcer, peripheral were removal that
pre-operative data. 250 arterial disease, previous significant of GSV/SSV, followed Rates of
duplex; reflux No mention patients trauma to the leg, general illness and extrafascial were recurrence
based on a of how the attended 2 drug or alcohol abuse. ligation of removal of and
randomised trial. randomised year follow- perforators, GSV/SSV, reoperatio
Baseline characteristics: Poorly
155
Annals of vascular sequence up. Unclear and stab extrafascial n (dealt

was drawn described (but available in Blomgren avulsions of ligation of
surgery 2006; 20: how many legs with in
up. 2005). Overall mean (range) age was tributaries. perforators,
30-34. were involved detail in
47 (22-73) and 71% were women. 45 and stab
in the study. Blomgren
(NB – Same study Study with bilateral surgery, 16 in duplex avulsions of
involved 20 group and 29 in no duplex group 2005)
as Blomgren No reports of tributaries.
26
2011 and surgeons. any who did (p=0.030. Skin changes present in
24
Blomgren 2005 ) not complete 18%, with no differences between
treatment. the groups. An important
confounder was the surgery used, as
this differed between groups. The
duplex group had more patients than
the non-duplex group with removal
of the GSV and SSV, and less patients
in the duplex group than the non-
duplex group had avulsions.
Results:
Duplex No duplex
patient assessed symptoms 15/130 19/120
operated limbs unchanged or worse at 2 years compared to baseline
Rates of recurrence and reoperation significantly higher in no duplex group (more details given in Blomgren 2005)
Quality of life – SF-36 domains No significant difference between the groups for any SF-36 domain at 1 or 2 years. The
results were the same when patients with bilateral and unilateral varicose veins surgery
were analysed separately. No data given for each group.
1
156
1 Table 46: Blomgren 200524
Reference Study type No. of patients Patient characteristics Intervention Comparison Length of Outcome Source of
follow-up measures funding
Blomgren L, RCT. Sealed 308 randomised Inclusion: Primary varicose veins, with Pre-operative No pre- 2 years Reflux at 2 None
Johansson G, envelope but 15 initially an indication for surgery (in the view Duplex scan, operative months
Bergqvist D. system used excluded because of the surgeon). using a duplex
Randomised for allocation of refusal, colour flow scan. (But Reflux at 2
clinical trial of concealment. pregnancy and Exclusion: pure cosmetic complaints, duplex some years
routine If both legs remote residency. previous venous surgery or machine surgeons
preoperative included, In the duplex sclerotherapy, history of suspected or (Acuson did a pre-
duplex imaging both given group 8 (8 legs) manifest deep venous thrombosis, XP128 and operative
before the same were excluded (2 active or healed leg ulcer, peripheral Acuson hand held
varicose vein randomisatio patient request, 2 arterial disease, previous significant Sequioa 512). Doppler
surgery. British n (i.e. inclusion criteria trauma to the leg, general illness and Reflux with a scan).
Journal of randomised violation, 2 moved drug or alcohol abuse. duration of
Surgery 2005; by patient). to remote region, >0.5 seconds
157
Baseline characteristics:
92: 688-694 2 pregnancy). In was regarded
No mention Surgical
the no duplex Duplex no duplex as significant.
(NB – Same of how the procedures
group; 7 (7 legs) (Some
study as randomised legs 166 177 that
were excluded (4 surgeons also
Blomgren 2011 sequence was followed
patient request, 2 M:F 44:122 43:134 did a pre-
and Blomgren drawn up. were
inclusion criteria operative
2006) removal of
violation, 1 moved age 47.9(11.1) 44.6(12.4) hand held
Study GSV/SSV,
to remote region). Doppler
involved 20 CEAP >C3 29/166 22/177 extrafascial
This left, by the scan).
surgeons. ligation of
point of the GSV stripping 125/166 83/177
Surgical perforators,
duplex
SSV removal 8/166 4/177 procedures and stab
intervention, 148
that followed avulsions of
patients (166 legs) GSV + SSV 0/166 1/177
were tributaries.
in the duplex removal
removal of Most done
group and 145
local 33/166 89/177 GSV/SSV, under
patients (177 legs)
phlebectomie extrafascial general
in the no duplex s done
group. ligation of anaesthetic.

perforators, Naturally, in
and stab the absence
avulsions of of duplex
Loss to follow-up;
tributaries. assessment,
2 months: Duplex Most done the
– 5 people (6 legs); under predetermi
No duplex – 8 general ned course
people (11 legs). anaesthetic. based on
Importantly, clinical
2 years: Duplex – in the duplex examinatio
35 people (39 group the n was
legs); No duplex – duplex adhered to.
39 people (48 assessment
legs). led to the
158
alteration of
surgery from
the pre-
determined
course in
44/166 legs.
Results: Analysis was done by legs. For reflux, intention to treat results given unless stated.
Duplex No duplex
10/160 37/166
SFJ reflux at 2 months
4/160 9/166
SPJ reflux at 2 months
14/160 44/166
SFJ and/or SPJ reflux (i.e. reflux anywhere!) at 2 months
14/127 44/129
SFJ reflux at 2 years
7/127 13/129
SPJ reflux at 2 years
19/127 53/129
SFJ and/or SPJ reflux (i.e. reflux anywhere!) at 2 years
3/145 (including patient with phlebectomies at 14/147
Need for further operation in first 2 years (indication was persistent or
another hospital)
recurrent symptoms, or patients’ wish)
Adverse events
DVT at 2 years 0/145 0/147

104/145 86/147
Proportion with improvement in CEAP category at 2 years
15/145 19/147
Proportion with skin changes (C4+) at 2 years (baseline difference, but
more in group 1 at baseline, so does not affect validity of result on right)
159
25/145 38/147
Proportion with oedema (C3) at 2 years (baseline difference, with more in
group 2 at baseline, which threatens the validity of the result on right)
1
2
1 Table 47: Blomgren 201126
Blomgren L, RCT. Sealed 308 randomised but Inclusion: Primary varicose veins, Pre- No pre- 7 years Reflux at 7 None
Johansson G, envelope 15 initially excluded with an indication for surgery (in operative operative years
Emanuelsson system used because of refusal, the view of the surgeon). Duplex scan, duplex scan.
L, Dahlberg- for allocation pregnancy and remote using a (But some
Akerman, concealment. residency. In the Exclusion: pure cosmetic colour flow surgeons did
Thermaenius If both legs duplex group 8 (8 legs) complaints, previous venous duplex a pre-
P, Bergqvist included, were excluded (2 surgery or sclerotherapy, history of machine operative
D. Late both given patient request, 2 suspected or manifest deep venous (Acuson HHD scan).
follow-up of a the same inclusion criteria thrombosis, active or healed leg XP128 and
randomised randomisatio violation, 2 moved to ulcer, peripheral arterial disease, Acuson
trial of n (i.e. remote region, 2 previous significant trauma to the Sequioa
leg, general illness and drug or Surgical
routine randomised pregnancy). In the no 512). Reflux
alcohol abuse. procedures
duplex by patient). duplex group 7 (7 legs) with a
that
imaging were excluded (4 duration of
160
No mention Baseline characteristics: followed

before patient request, 2 >0.5 seconds
of how the were
varicose vein inclusion criteria Duplex no duplex was
randomised removal of
surgery. violation, 1 moved to regarded as
sequence was legs 166 177 GSV/SSV,
British remote region). This significant.
drawn up. extrafascial
Journal of left, by the point of M:F 44:122 43:134 (Some
ligation of
surgery 2011; the duplex surgeons
Study perforators,
98: 1112- intervention, 148 age 47.9(11.1) 44.6(12.4) also did a
involved 20 and stab
1116.(NB – patients (166 legs) in pre-
surgeons. CEAP >3 29/166 22/177 avulsions of
Same study the duplex group and operative
tributaries.
as Blomgren 145 patients (177 legs) GSV stripping 125/166 83/177 HHD scan).
Most done
2005 and in the no duplex
SSV removal 8/166 4/177 under
Blomgren group.
general
2006) GSV + SSV 0/166 1/177
Loss to follow-up; Surgical anaesthetic.
removal
procedures Naturally, in
2 months: Duplex – 5 local 33/166 89/177 that the absence
people (6 legs); No phlebectomie followed of duplex
s done
duplex – 8 people (11 were assessment,
legs). removal of the
GSV/SSV, predetermin
2 years: Duplex – 35 extrafascial ed course
people (39 legs); No ligation of based on
duplex – 39 people (48 perforators, clinical
legs). and stab examination
avulsions of was adhered
7 years:
tributaries. to.
Clinical examination:
Most done
Duplex: 62 people (70
under
legs); No duplex:
general
56(88).
anaesthetic.
Interview and info
Importantly,
from patient notes:
in the
Duplex: 34 people (42
161
duplex
legs); No duplex:
group the
32(43).
duplex
assessment
led to the
alteration of
surgery from
the pre-
determined
course in
44/166 legs.
Results:
Duplex No Duplex
SFJ reflux at 7 years 11/95 38/99
SPJ reflux at 7 years 2/95 9/99

SFJ and/or SPJ reflux (i.e. reflux anywhere!) at 7 years 13/95 46/99
Condition of treated leg compared to before surgery (Unchanged or worse) 16/123 28/108
at 7 years
Quality of life – SF-36 at 7 years No data given, apart from statement that there were no differences in any SF-36
variable between groups (reporting bias).
Reoperation or scheduled for reoperation at 7 years 15/124 38/134
Complications of varicose veins at 7 years
Venous ulcer 0/70 0/88
Hyper-pigmentation or eczema 3/70 9/88

162
1
2
1 Table 48: Smith 2002251
Smith JJ, Brown RCT. 149 Inclusion: patients with Pre-surgical duplex No pre- 12 months Quality of None
L, Greenhalgh patients primary varicose veins assessment. Duplex surgical life stated
RM, Davies AH. Randomisatio randomised without venous ulceration. carried out by an duplex
Randomised trial n done with . None lost experienced vascular assessment. Reflux
of pre-operative sealed to follow-up Baseline characteristics: No technologist. Accuson
colour duplex envelope and none details on demographic 2000 scanner with 7.5 Unclear, but it
marking in system with discontinue characteristics. MHz linear array probe is likely these
primary varicose allocation by d was used. Hand held patients did
a third party. However, clear information have hand
vein surgery: interventio HD assessment also
Randomised on the surgery each group held Doppler
outcome is not n. carried out, using an
by patient not received. The groups were assessment.
improved. Eur j Imax continuous wave
leg. very similar for the number of N=97
Vasc Endovasc doppler with 8MHz
“HSL/strip/phlebectomy”
Surg 2002; 23: probe.
procedures, and
336-343.
163
“phlebectomy alone” Common procedures:

procedures, but the duplex operative procedures
group had more SPJ and were done with
phlebectomies, and more general anaesthetic.
“short and long saphenous For long saphenous
system together” procedures. system, flush sapheno-
However the latter two femoral transfixion
classes only comprised a very with division of
small proportion of all surrounding branches
procedures and so broadly and removal of the
the surgical procedures were great saphenous vein
comparable. Quality of life was carried out. For
was described as comparable small saphenous vein
for all quality of life measures. system, flush sapheno-
popliteal transfixion
and removal of the
small saphenous vein
was carried out.
Tributary varicosities
removed with
phlebectomy hooks or
mosquito clips. N=92
Results:
Duplex No Duplex
Reflux SFJ 6weeks 1/92 1/97
Reflux GSV 12 months 8/92 9/97*
Reflux SSV 6 weeks 4/92 6/97
Reflux SSV 12 months 6/92 8/97
Reflux perforators 6 weeks 1/92 5/97
Reflux perforators 12 months 4/92 15/97
164
Development of new branch varicosities at 12 months 8/92 9/97

Aberdeen Questionnaire (AVVQ) at 6 weeks (NO VARIANCE 10.85 15.85 (P=0.034)
GIVEN)
Aberdeen Questionnaire (AVVQ) at 12 months No difference reported [p=0.187] (data in low resolution figure, no data in text)
SF 36 6 weeks No diff reported p>0.38 (all domains)
SF 36 12 months No diff reported p>0.15 (all domains)
* paper reports a total of 17 having GSV at 12 months, and then “of which 8 were in the duplex group and 19 in the no duplex group”. This was assumed to be a
typographical error, and that it should have been 9 rather than 19.
1
2
G.4 Chapter 8 – conservative management
2 G.4.1 Compression vs. no treatment
3 Table 49: Anderson 19907

No. of Interventio Compariso Length of Outcome Source of
Reference Study type patients Patient characteristics n n follow-up measures funding
Anderson JH, Randomised 72. Mean age 40 years (range 20-61 years). Full length Placebo is Length of Patient assessed not
Geraghty JG, cross-over trial. 6 did not 39 patients spent at least 2/3 of their hosiery not each symptoms: stated
Wilson YT, Four groups were complete time at work standing. fitted to described. treatment – (using visual
Murray GD, involved – the trial. give a It is likely it 4 weeks. analogue scale
McArdle CS, Paroven alone; Not Inclusion: patients on waiting list for pressure at was a (VAS).
Anderson JR. hosiery and possible varicose veins surgery (mean of 6 the ankle of sham pill,
Paroven and placebo; paroven to months on list) who indicated the 30-40 but
graduated and hosiery; and determin presence of at least 2 of the following mmHg. unclear.
compression placebo alone. e the symptoms: leg pain, heaviness, itch, Hosiery
165
hosiery for The subjects were numbers cramps, swelling. removed in

superficial randomised to for each bed.
venous start in one of treatment
insufficiency. these 4 groups, Exclusion: If the only complaint was
group. No Used for 4
1990; 5: 271- and treatment cosmetic distress. Age >65 years; clinical
ITT weeks
276. sequences were evidence of peripheral arterial disease
reported.
balanced within (PAD), concurrent treatment with
2+
groups of 12 in diuretics, Ca antagonists, NSAIDs,
three Latin vasodilators, or corticosteroids; history
squares. of DVT.
Only the results
from placebo Baseline characteristics: Not given for
alone and hosiery the 4 randomised cross-over groups.
and placebo are
included in this
evidence table.
No wash-out
No. of Interventio Compariso Length of Outcome Source of
Reference Study type patients Patient characteristics n n follow-up measures funding

periods described
– but patients
were supposed to
attend for post-
test outcome
assessment after
50 days, so this
implies a wash-
out of 22 days.
Details of
randomisation
and allocation
concealment not
given. No
evidence of
blinding.
166
Results: VAS scores at the end of the 4 week treatment period are given. The risk of bias from order effects (carry-over) minimised by Latin squares method of ensuring
balanced ordering of treatments.
VAS (higher the worse the severity) Compression [mean(SE)] Placebo [mean(SE)] p value (post-hoc)
Pain 34.7 (3.6) 37.6 (3.6) 0.06
heaviness 34.1(3.8) 36.3 (3.5) 0.39
itch 32.0 (3.8) 30.5 (3.9) 0.56
swelling 28.2 (3.6) 35.3 (3.7) 0.13
night cramps 22.4(3.1) 24.9 (3.0) 0.24
body image concerns 43.2(4.6) 41.1 (4.7) 0.43
Author's conclusions: No conclusions made for hosiery alone.
1
2
1 Table 50: Benigni 200319
No. of Interventi Comparis Length of Outcome Source of

Reference Study type patients Patient characteristics on on follow-up measures funding
Benigni JP, RCT. Multi-centre cross- 125. ITT Inclusion: female patients aged 18-75 Class 1 Placebo: At end of Patient not
Sadoun S, over trial, with 7 day analysis years, with early stage Chronic Venous knee-high regular double assessed stated
Allaert FA, Vin washout period. used. Disease (CVD) of the legs. Thread veins, graduated knee-high cross-over symptoms:
F. Efficacy of Randomised, but method Used on non-saphenous varicose veins (<3mm) compressi stocking treatment global
Class 1 elastic not mentioned. No those or ankle oedema without skin changes. on used as a period discomfort in
compression allocation concealment patients Symptoms including pain, heavy legs, stockings “referenc (35 days) legs, pain,
stockings in mentioned. Double who had cramps, paraesthesia or ankle swelling. (13-20 e” heavy legs,
the early blinded, but few details worn Global painful leg discomfort lasting >8 hPa). stocking, cramps,
stages of given. “study days, and with a visual analogue scale Given for providing swelling in
chronic stockings (VAS) of 4/10 or more on the day of 14 days, <10hPa. ankles,
venous at least testing. Competent deep venous trunks, and worn Very mood, daily
Withdrawal: 8 by day 14,
disease. once” and competent greater saphenous veins for a similar in work activity.
further 3 by day 21 and
International who had (<5mm), competent lesser saphenous minimum appearan
further 3 by day 35
Angiology been veins (<4mm), competent calf of 6 hours ce. Given Adverse
(total=14). Ignoring losses
2003; 22: 383- perforating veins, shown by a venous for 14
167
in the wash-out period evaluated per day. events.

392 at least refilling time of >24 seconds and an days, and
the placebo group lost 7
once. ankle diameter of 20-26cm and a worn for
over the two periods, but Cross
maximum calf diameter of 33-43cm. a
the intervention group over
minimum
lost only 4. study, so
Exclusion: male patients, suffering from of 6 hours
half the
chronic or severe disease. Symptoms of per day.
NB: For all outcomes participan
signs in the legs due to pathology of ts were
(except mood and daily
cardiac, renal, hepatic, metabolic, randomis Cross
work activity) the
neurological, osteo-articular or ed to over
detailed results given in
traumatic origin. BMI>30. Any risk receive study, so
the paper are ONLY from
factors for worsening CVD: recent this half the
the first phase, PRIOR to
venous thrombosis, pregnancy or treatment participan
cross-over. Hence this is
childbirth within 6 months. first, prior ts were
not truly a cross-over
Past history of DVT. Skin changes, to the 7 randomis
study. Full cross-over
permanent ankle oedema. Ultrasound day ed to
results were given for
evidence of valvular incompetence in washout receive
mood and daily work
the sapheno-femoral or sapheno- period. this
activity but no reasons

are given for the lack of popliteal junctions, obstacles or reflux in treatment
full cross-over results for the deep venous network. Use of first, prior
the other variables. This Calcium channel blockers, anti- to the 7
opens up the risk of coagulants, diuretics, anti-inflammatory day
publication bias and drugs, Vitamin C, recent hormonal washout
reduced confidence in treatment, recent phlebotonic or pain period.
the validity of the medications, recent elastic compression
presented findings. All and indications for sclerotherapy or
that is stated is that the surgery.
global discomfort, pain,
heavy legs, cramps and Baseline characteristics: No significant
swelling measured at the differences between the two
end of the cross-over randomised groups (control first versus
stage were “similar”. intervention first) for age, weight,
height, professional status, risk factors
or past medical history. No baseline
168
differences in outcome variables.

Results: NOTE: Full cross-over results are given for mood and daily work activity only. For all others, results pertain to those recorded at the end of the first phase
(before cross-over). All that is stated is that the group differences in global discomfort, pain, heavy legs, cramps and swelling measured at the end of the cross-over
stage between the two treatment groups were “similar” to those at day 14.
Compression [mean VAS (sd)] Placebo [mean VAS (sd)] p value
Global painful discomfort in the legs 1.8 (1.7) 3.1 (2.1) <0.05
during days 7-14
Global painful discomfort in the legs 1.4 (1.8) 2.9 (2.1) <0.01
at day14
Mood (unclear if a high score 1.1 (1.7) 1.5 (1.9)
represents good or bad mood)
Daily work activity (unclear if a high 1.1 (1.6) 1.6 (1.8)
score represents high or low activity)
Compression [count with no Placebo [count with no change or a
change or a deterioration] deterioration]

Pain at day 14 27/61 37/53 0.0215
Heavy legs at day 14 20/59 35/54 0.0025
Cramps at day 14 37/61 44/55 0.0379
Ankle swelling day 14 35/61 43/53 0.0240
No outcome reporting for paresthesia, leg volume, changes in venous refilling time or venous pump power, except that no difference between compression and
placebo.
Adverse events were reported as being significantly worse for those using the placebo stockings – slipping sensation on the leg, warming sensation, a feeling of
pressure on the legs.
Author's conclusions: The wearing of class 1 graduated compression knee-high stockings (10-15 mmHg at the ankle) for a 15 day treatment period results in a
significant improvement in the symptomatology and in the quality of life criteria in patients presenting with early-stage CVD of the lower extremities.
1
169
1 Table 51: Junger 1996126
Junger M, Cohort study. 20 Inclusion: Chronic Venous 2 weeks of short- Before and 2 weeks Patient assessed None
Galler S, Klscz Insufficiency (CVI) class I (n=7) stretch bandaging, after design. and 4 symptoms: stated
T, Steins A, and II (n=13), according to followed by 2 more weeks. pain, tautness,
Hahn M. Widmer’s classification; weeks with class II swelling,
Improvement compression itching, and
of cutaneous Baseline characteristics: stockings (the 3 feelings of cold,
microangiopa Gender: 10 men; 10 women; with previous DVT heat and
thy by mean age 54.9 years(9.5); used class III). restriction (on a
compression scale of 0-3
3 with previous DVT; all with
therapy in (max complains)
ankle brachial index>1.0; all had
chronic
reduced venous refill time (20(12)
venous
seconds); Doppler showed
insufficiency.
incompetence of:
Phlebology
170
Suppl. 1996; • deep veins in 7 patients

1: S10-S13. • superficial veins in 12
patients
• perforating veins in 6
patients.
Results: Reported that subjective treatments in all patients decreased during treatment, except for the feeling of coldness, which increased again during the second
part of the study using compression stockings. There were no complaints by patients about feelings of constriction during the second part of therapy. No numerical
data presented.
Author's conclusions: No relevant conclusion with reference to patient symptoms.

2
3
1 Table 52: Krijnen 1997139
No. of Interventi Compariso Length of Outcome Source of

Reference Study type patients Patient characteristics on n follow-up measures funding
Krijnen RMA, Quasi-randomised controlled 114 in total. All male factory workers with a Below Not 3 months Patient not
de Boer EM, trial. 101 in the predominantly standing job from knee class described, assessed stated
Ader HJ, The truly random part was control (n=50) 14 factories. All with evidence of II (30-32 but symptom
Osinga DSC, the allocation to treatment and chronic venous insufficiency (CVI). mmHg) appears to s
Bruynzeel DP. and control groups. No compression 40 had complications including seamless be no
Compression details of randomisation (n=51) groups. trunk varicosis, compressi treatment. Adverse
stockings and method used. No evidence In the lipodermatosclerosis, on events
rubber floor given of allocation compression hyperpigmentation, atrophy stockings.
mats: do they concealment. group one blanche or dermatitis. None had Used
benefit There was a further, non- refused to leg ulcers. during
workers with random splitting of the wear hosiery working
chronic treatment patients to the and a further 5 Inclusion: Evidence of CVI by hours only.
venous two treatments – were lost to physical examination, Doppler
insufficiency compression stockings or the follow-up, for ultrasound investigation and light
and a standing
171
use of rubber mats to stand “unrelated reflective rheography. Standing

profession? on. This was decided by the reasons”. factory job.
JOEM 1997; 9: safety and hygiene A further 15
889-894. conditions of the factory stopped Exclusion: Individuals with only
concerned. In 10 factories wearing the intracutaneous or only a few
compression stockings were stockings small varicose veins.
used, and in 4 rubber mats every day
were used. It is conceivable during the
that this could cause bias by study, for Baseline characteristics: No
the compression group being reasons comparison of anthropometric
from a certain type of factory including poor baseline characteristics. At
(specific hygiene and safety fit or skin baseline, the compression and
conditions) and the placebo problems. control groups were similar for
group being from any type of proportion having pain, with
factory (perhaps those 10/30 in pain in the intervention
16 were lost to group and 13/34 in the control
working in a certain type of follow-up from
factory – i.e. heavy industry - group [estimated from graph] (no
the control statistical analysis done), and the
would have different risk group.

factors). However this would control group [19/34, estimated
probably be a small effect as No ITT from the graph] had a slightly
only 13 subjects out of 64 in performed so lower proportion of people than
the treatment group were analysis the compression group [21/30]
put in the mat group. restricted to with a tired feeling at baseline.
the 30 who This slight difference will have
Only results for compression wore the favoured the control group, and
versus control are included in stockings thus does not invalidate the post-
this evidence table. almost every intervention finding that the
day, and the compression group had a lower
34 in the proportion of people with tired
control group legs than the control group.
who attended
follow-up.
Results: Post-test results given. Despite the lack of confirmation that the groups were similar at baseline for the variables below, the differences seen are unlikely to
172
have led to a bias favouring compression. In particular, for the tired feeling, less control were in pain at baseline which would favour the control group.
Compression Control p value

Patients with complaints of 8/30 18/34 (estimated from graph) <0.005
tired legs (proportion of
subjects) at 3 months
Patients with complaints of 2/30 12/34 (estimated from graph) <0.05
pain (proportion of subjects)
at 3 months
Patients with overall 17/30 4/50 (16 were reported lost to follow-
decrease in complaints at 3 For the 15 not wearing stockings every up, and no ITT was done, so this may
months day: 4/15 be a typographical error, and the
correct result may be 4/34).
Patients in favour of 26/45
continuing stockings beyond
study duration.

Adverse events
Reasons for non-compliance
(only the 15 who did not
wear the stockings everyday
were asked. Each person
could give only one reason
each)
itch 2/15
red and swollen skin 2/15
too tight 5/15
Author's conclusions: Compression stockings appeared to be superior [....] with regard to applicability, [and] diminishing subjective complaints....
1
173
1 Table 53: Lurie 2011154
Reference Study type No. of patients Patient characteristics Intervention Compari Length of Outcome Source of
son follow-up measures funding
Lurie F, Observatio 150 were originally Consecutive patients with primary Compression Pre 2-6 weeks. Patient None
Kistner RL. nal single selected. These were CVD were selected according to the therapy by 20- versus reported quality stated
Trends in group divided into two criteria below. 30mmHg post (2-6 of life: Disease
patient before- groups who both knee-high weeks of specific SQOR-V
reported after study. initially had Inclusion: confirmed primary graduated treatmen form
outcomes of compression therapy aetiology; unilateral involvement; compression t).
conservative (one group later had great saphenous vein reflux; C2-C4; stockings Patient
and surgical endovenous no use of compression for at least given for 2 to assessed
treatment of radiofrequency one year. 6 weeks. symptoms:
primary ablation whilst the Lifestyle Symptom score
chronic other continued with advice (weight
venous conservative Exclusion: CEAP stages C5-6; small loss, exercise
disease treatment, and the saphenous vein involvement; and frequent
contradict results of these later current or recent use of leg elevation)
174
current treatments will not compression; non-compliance with ALSO given.

practices. be included here). compression therapy; difficulty
Annals of However, since the completing quality of life form;
Surgery 2011; data were problems with English language
254: 363-367. continuous it is not comprehension.
possible to combine
the results for the Baseline characteristics:
initial compression Gender: 38% male;
phase, so data from Age: mean age 54.4(11.7);
the larger group of
CEAP stage: C2: 32.2%; C3: 24%;
121 patients is given.
C4: 43.8%;
Results: mean (sd) given. N=121
pre-compression post-compression p value
Symptom score (this is made up of part of the SQOR-V form, comprising 16.9(9.8) 6.3(5.8) not given
severity of pain, heaviness, itching, night cramps, heat or burning, tingling,
Reference Study type No. of patients Patient characteristics Intervention Compari Length of Outcome Source of
son follow-up measures funding
throbbing, restless legs, swelling. The symptom score is the sum of the
scores of these 9 symptoms, each on a 6 point scale; a higher score
indicates worse symptoms, with 54 the worst score)
SQOR-V form (this is made up of several domains, with higher scores 62.5(20.6) 48.9(17.9) not given
indicating worse disease specific QoL; 190 is the maximum score)
Author's conclusions: compression therapy selectively improves some symptoms....the QOL outcomes of compression therapy were better than the symptom
response.
1
2
175
1 Table 54: Motykie 1999176
Reference Study type No. of Patient characteristics Intervention Compariso Length of Outcome Source of
patients n follow-up measures funding
Motykie GD, Before-after 112. Those Inclusion: Patients with chronic 30-40 mmHg Post 1 month and Patient None
Caprini JA, design with venous insufficiency (CVI). compression treatment 16 months assessed stated
Arcelus JI, observational bilateral stockings for 16 compared (treatment symptoms
Reyna JJ, trial, without symptoms Exclusion: patients currently months. to pre- continued to
Overom E, control group. included, wearing compression stockings. Hours per day and treatment. end of Adverse
Mokhtee D. Therefore but unclear night-use unclear. follow-up). events
Evaluation of subject to how many. The stockings
therapeutic uncontrolled Baseline characteristics
varied
compression threats to Gender: 95 females, 17 males;
• 36% thigh
stockings in internal Age: range 27-85 years (mean 46.8);
lengt,
the validity, such No prior CVI or varicose veins
treatment of as time • 17% mid-thigh
treatment: 95/112.
chronic effects, length
Prior treatment 17/112
venous placebo • 47% knee or
• 11/17 sclerotherapy
176
insufficiency. effects etc. calf length

Dermatol • 6/17 stripping surgery.
Surg 1999;
25: 116-120 Flawed statistics provided for CEAP
class. Authors gave percentages of
participants with the main symptom
characteristic of each CEAP class
which is not helpful as some
symptoms will span multiple CEAP
grades (i.e. instead of “swelling”
indicating those with swelling but
NOT pigmentation or ulceration,
which would be equivalent to
CEAP3, the swelling statistic
included any of those also with
pigmentation and ulceration, which
was therefore no longer equivalent
to CEAP3).
Results: mean (sd) given. Patients with bilateral symptoms given were given bilateral stockings, but number with bilateral symptoms unknown. Hence unclear how many
data points there were.
Patient assessed symptoms (1-5 scale, pre- 1 month post-compression 16 months post-compression p value (Wilcoxon signed ranks test
with 1=minimal problem and 5=maximal compression used, despite the presentation of sds)
problem)
swelling 2.45(1.25) 1.47(0.83) 1.13(0.51) P<0.001 for comparison between

baseline and 1 month for all variables.
pain 2.94(1.29) 1.77(1.09) 1.38(0.69)
P<0.0001 for comparison between
discolouration 2.76(1.29) 2.23(1.22) 1.81(0.99) baseline and 16 months for all variables.
cosmetic problems 3.03(1.41) 2.50(1.41) 1.98(0.99)
activity tolerance 2.33(1.35) 1.71(1.19) 1.38(0.73)

177
depression 1.72(1.12) 1.42(0.87) 1.29(0.81)
sleep problems 2.00(1.25) 1.46(0.99) 1.24(0.63)
Adverse events (scale the same as for

patient assessed symptoms)
numbness NA 1.41(1.20) 1.20(0.92) NA
Sweating 1.45(1.00) 1.23(0.83)
Itchiness 1.40(0.97) 1.14(0.78)
new pain 1.44(1.20) 1.12(0.80)
Compliance (still wearing stockings) 92/112 78/112

Author's conclusions: Therapeutic graduated compression stockings are an effective treatment for CVI of the lower extremities
1
1 Table 55: Pannier 2007201
Pannier F, Cross- 3072 Inclusion: Randomly recruited from a Patients with a NA Patient assessed None
Hofffmann B, sectional German city and environs; included history of symptoms stated
Stang A, questionnaire/ ALL residents, regardless of health varicose veins
Jockel KH, interview status; urban to city ratio of 2:1; were asked about Adverse events
Rabe E. study. 59% response rate; demographics their use of
Prevalence representative of the general medical
and German population; compression
acceptance stockings (MCS).
of therapy
with medical
compression mean BMI: 25.6(4.8);
stockings. 890 described as having varicose
Phlebologie veins.
2007; 36: 961 had history of chronic venous
178
245-249. sufficiency (CVI) at CEAP stages C2-6:

• C2: 439/961
• C3: 412/961
• C4: 88/961
• C5: 19/961
• C6: 3/961.
Results: 10.3%% (n=316) of all sample with CEAP stages C2-6 had used MCS (32.9% of those with C2-C6). At the time of interview, 210/316 (66.5%) who had ever
received MCS were not wearing them at the time of interview, and had not worn them in the last 4 weeks, indicating a compliance figure of 33.5%.
The groups who had used them in the last 4 weeks and not used them in the last 4 weeks differed in terms of the proportions from each CEAP class, with the most
severely affected tending to be more compliant:
CEAP Medical compression stockings used, but not in last 4 weeks Medical compression stockings used in last 4 weeks
C2 96/210 (21.9%) 26/106 (5.9%)
C3 78/210 (18.9%) 50/106 (12.1%)

C4 28/210 (31.8%) 20/106 (22.7%)
C5-C6 8/210 (36.4%) 10/106 (45.5%)
For those who used MCS currently, patients usually wore their MCS 5 or more days per week (73%) and for 8 or more hours per day (89.4%).
71.3% of the interviewed participants using MCS said their medical condition had improved with MCS therapy. This included:
• reduction in swelling (84.2%)
• reduction in heaviness (89.4%)
• reduction in leg pain after prolonged standing (60.9%)
• reduction in tension in the legs (78.9%)
Most patients could not remember the compression class, but available evidence suggested:
• class 1: 13
• class II: 149
179
• class III: 26
The types were:

• compression tights: 34%
• thigh compression stockings: 23%
• lower leg compression stockings: 41.1%
Adverse events were reported as:

• pruritis (8.4%)
• eczemas (1.6%)
• constrictions under the MCS (8.4%)
• slipping of stockings (3.6%)
Author's conclusions: An improvement of their condition was attributed to [MCS] by 80% of patients.
1
2
1 Table 56: Raju 2007217
Raju S, Hollis Case series. 3144 Inclusion: Stated that “new” None. This was an NA Compliance None
K, Neglen P, Extremely chronic venous disease (CVD) observational study stated
Mississippi F. limited cases, but then also stated that of CVD patients,
Use of methodology they had been under care with and only 37% were
compression in terms of GP or other specialists for using stockings.
stockings in being open to variable periods of time;
chronic multiple risks
venous of bias. Baseline Characteristics:
disease:
• Age: median 58 (range 17-
patient
92);
compliance
and efficacy. • Gender: Male: Female =1:2
Ann Vasc • CEAP stages
Surg 2007; o CEAP 0-2: 67%
180
21: 790-795 o CEAP 3: 22%

o CEAP 4: 4%
o CEAP 5: 4%
o CEAP 6: 3%
• Aetiology was primary in 58%
and post-thrombotic in 42%.
Results:
21% of patients reported full “compliance”. 12% used them most days and 4% some days. The other 63% did not use the stockings at all or had abandoned them after
a trial period in the past. Compliance did not differ according to CEAP class, gender or previous DVT. Compliance did improve with longer duration of treatment
Reviewer’s comment: As not all the patients in the study had been prescribed stockings, these daily use figures of 21%, most days use figures of 12% and occasional use
values of 4% do not really equal compliance, as compliance must make use of the number prescribed them as the denominator. Clearly a patient never prescribed a
treatment cannot be described as non-compliant. As only 75% of the patients had been recommended stockings by a doctor, the true full compliance figure would be
21/0.75= 28%; full and partial compliance would be (21+12)/0.75=44% and full, partial and minimal compliance would be 21+12+4)/0.75=49.33%.
Primary reasons for non-use of stocking, of those that were recommended stockings by their doctor
unable to state a reason 40%
lack of efficacy 20%
poor fit/cut off circulation 17.3%
too hot 9.3%
soreness 2.67%
needs application 2.67%
assistance
cosmetic reasons 2.67%
itching/dermatitis 2.67%
worsening of symptoms 1.33%
lack of self-discipline 0.67%
Cost 0.53%
Work-related 0.27%
181
Author's conclusions: Non-compliance is very high in patients with CVD regardless of age, sex, aetiology of CVD, duration of symptoms or disease severity.
1
1 G.4.2 Compression vs. interventional treatment
2 Table 57: Michaels 2006170
Michaels JA, RCT. 246 randomised. Taken from consecutive referrals Use of Stripping 1 and 2 Quality of NHS HTA
Brazier JE, Computer Although there to vascular units at two large compression surgery, done years. life programme.
Campbell WB, randomisati were a number of hospitals in the UK. hosiery, under general
MacIntyre JB, on and bilateral cases, the Inclusion: primary varicose veins alongside anaesthetic Patient
Palfreyman SJ, group total number of with sapheno-femoral or sapheno- lifestyle and usually as assessed
Ratcliffe J. allocation legs is not popliteal reflux. advice a day case. symptoms
Randomised by reported. In the Exclusion: co-existing disease or relating to For patients
clinical trial telephone. surgery group disability precluding surgery; exercise, leg with affected
comparing Thus there were 18.1% elevation, Patient
complications of varicose veins; great
surgery with allocation with bilateral and weight / satisfaction
veins < 5mm in diameter in lower saphenous
conservative concealmen surgery. However it thigh. diet veins(GSV):
treatment for t very likely. appears that management. Adverse
182
Baseline comparison. Reported no flush ligation

uncomplicated No blinding randomisation was Duration of at the events
group differences.
varicose veins. reported only by the worst treatment saphenofemo
British Journal for patient leg, and so results conservati surgery unclear. ral junction,
of Surgery or relating to the ve with stripping
2006; 93: 175- researchers better leg are not F:M 87:35 83:41 of the GSV to
181 , or included here. Age 49.5 49 knee level,
assessment with multiple
height 168 167.8
AND of the Of the 122 phlebectomie
outcomes randomised to BMI 26.9 26.4 s.
relevant to conservative smokers 21.3% 26.6% For patients
Michaels JA,
the review treatment, all with affected
Campbell WB, Family 70.5% 73.4%
question. received short
Brazier JE, history
MacIntyre JB, Intention to treatment. 21 lost of VV. saphenous
Palfreyman SJ, treat to follow-up at 1 veins(SSV):
carried out year, leaving 101 Family 7.4% 16.1% sapheno-
Ratcliffe J, history
Rigby K. in terms of for analysis. A popliteal
of leg
Randomised those further 63 also ulcers ligation at the
clinical trial, refusing the discontinued Previous 2.1 2.1 sapheno-
observational randomised compression over pregnan femoral
study and treatment the following 3 cies junction, with
assessment of being kept years, opting for (mean) stripping of
cost- in that surgery. However the SSV in
effectiveness group and these were kept in SF-6D 0.74(0.11) 0.73(0.1) some
of the analysed. the analysis in the EQ-5D 0.77(0.18) 0.76(0.19) patients, with
treatment of However no conservative multiple
varicose veins imputation treatment group, phlebectomie
(REACTIV trial). carried out as per ITT. s.
Health for those
technology failing to Of the 124
assessment attend allocated to
2006; vol 10: follow-ups. surgery, 109
183
number 13. received surgery. 9

This second refused surgery
article covers and had
the same trial conservative
with the same treatment instead,
patients, and and 6 deferred.
contains the These 15 were kept
same in the group, and
information as analysed, with ITT.
the first study, 43 lost to follow-up
with some at 1 year, and so
small additions there were 81
(in red). available for
analysis at 1 year.
Some of the 43 lost
to follow-up were
contacted and
reported that their
withdrawal was
not due to lack of
efficacy or adverse
events, but mostly
because they were
well.
Results:
Outcome Conservative Surgery
SF-6D 1 yr mean(sd) 0.73(0.11) n=98 0.77(0.10) n=75
SF-6D 2 years mean(sd) 0.72(0.13) n=47 0.78(0.10) n=44
EQ-5D 1 yr mean(sd) 0.78(0.18) n=101 0.87(0.14) n=78
EQ-5D 2 years mean(sd) 0.85 (0.17) n=44 0.84 (0.21) n=34
SF-36 no overall scores given – only sub-scales given
184
Aching (proportion same or worse) at 1 yr 72/97 15/75

heaviness (proportion same or worse) at 1 yr 52/97 9/75
itching (proportion same or worse) at 1 yr 42/97 10/75
swelling (proportion same or worse) at 1 yr 31/97 8/75
cosmetic concerns (proportion same or worse) at 1 yr 75/97 13/75
Patient dissatisfaction at ?1 year (follow-up point unclear) 53/107 3/65
Adverse events
neural damage (footdrop resolving in 8/52) 0/122 1/124
post-op pain 0/122 3/124
phlebitis 3/122 0/124
1
G.5 Chapter 9 – interventional treatment
2 G.5.1 Stripping surgery vs. foam sclerotherapy
3 Table 58: Abela 20082

Source
No of Patient characteristics Length of Outcome of
Reference Study type patients Intervention Comparison follow-up measures funding
Abela R et RCT, UK. 90 Inclusion: Patients >18 years Stripping surgery via Reverse foam 2 weeks Post-op Not
al. Reverse consecutive old with CEAP 2 and 3 1) Standard stripping sclerotherapy: post thigh stated
foam Allocation limbs of 82 symptomatic primary (using a Babcock- 3ml of 1% sodium treatment. bruising
sclerotherap concealment via patients varicose veins (i.e. with SFJ type flexible stripper) tetradecyl (reported
y of the sealed envelopes. with and GSV reflux, confirmed or 2) Invagination sulphate by patients
great Randomisation incompeten by diagnostic duplex technique. (Fibrovein®) and
saphenous method unclear. ce of the ultrasound assessment. mixed with 3ml observers).
Tumescent
185
vein with GSV air resulting in

sapheno- resulting Exclusion: Not disclosed anaesthesia applied 6ml foam;
femoral from along the length of injected into
[Technical failures Baseline characteristics: Adverse
ligation varicose the GSV prior to collapsed vien via
occurred in 2 events,
compared to veins. stripping. All legs the angiography
patients in the Stand Inva Rev including
standard dressed post- catheter as this
standard stripping ard gina erse post-
and (74 of the 82 operatively with was withdrawn
group, 4 patients in stripp tion foa procedure
invagination patients had foam strip padding along the length
the invagination ing stri m pain (as
stripping: a unilateral applied externally of the vein (hence
group, and 3 ppi scle indicated
prospective saphenous over the length of ’reverse foam’).
patients in the ng roth by no. of
clinical incompeten the GSV track, which Proximal GSV tied
foam sclerotherapy era patients
series. ce and 8 had was secured using an 5cm distal to its
group. [BUT no. of py using
EUROPEAN bilateral elastic adhesive cut end and
people who analgesia).
JOURNAL OF incompeten Mean 46 47 45 bandage. 1 day post redundant few
withdrew from
VASCULAR & ce) age (18- (25- (22- op, drains removed, cm of vein
study was not
ENDOVASCU (rang 66) 67) 66) legs dressings taken excised. Complete
described]
LAR e) down and replaced filling of vein
Source

SURGERY. by Class II graduated checked by
2008;36(4):4 F:M 17:13 15: 22: compression ultrasonography.
85-490. ratio 15 8 stockings worn [NOTE: to ensure
continuously until uniformity
follow-up at Day 15. between the
procedures,
tumescent
anaesthesia
applied along the
length of the GSV
prior to
stripping.] All legs
dressed post-
operatively with
foam strip
186
padding applied
externally over
the length of the
GSV track, which
was secured using
an elastic
adhesive
bandage. 1 day
post op, drains
removed, legs
dressings taken
down and
replaced by Class
II graduated
compression
stockings worn
continuously until
Source

follow-up at day
15.
Results
Outcome Standard stripping Invagination stripping Reverse foam sclerotherapy
(n= 30 legs) (n= 30 legs) (n= 30 legs)
Post-op bruising Patient (%) Observer (%) Patient (%) Observer (%) Patient (%) Observer (%)
None 13 20 13 13 67 77
Moderate 50 73 70 80 30 23
Significant 37 7 17 7 3 0
Post-procedure pain Use of analgesic post-op (% patients)
No 5/30 (17%) 7/30 (23%) 23/30 (77%)
Occasional 25/30 (83%) 19/30 (63%) 7/30 (23%)
187
Regular 0 4/30 (13%) 0

Adverse events No clinically detectable adverse events attributable to the use of foam sclerotherapy were
reported post-operatively or during the follow-up period.
Author's conclusions: Standard stripping of the GSV and invagination stripping are not associated with major discomfort and problems in the early post-op period.
SFJ ligation and GSV reverse foam sclerotherapy yielded greater patient satisfaction with less post-op bruising and discomfort and reduced analgesic requirements.
(NOTE: data not reported in paper for the outcomes in bold)
1
1 Table 59: Bountouroglou 200630
Source
No. of Patient characteristics Intervent Comparis Length of Outcome of
Reference Study type patients ion on follow-up measures funding
Bountouroglo RCT. 60 Inclusion: Symptomatic primary Ligation Ligation 3 weeks AVVQ None
u DG, Azzam patients varicose veins due to GDV performe performe and 3
M, Kakkos SK, Allocation decided by incompetence; no previous treatment d at SFJ. d as for months
Pathmarajah random drawing of sealed for varicose veins; suitability for day GSV stripping
envelopes. With this form VCSS
M, Young P, case surgery. stripped under LA.
Geroulakos. of randomisation, from SFJ Varicositi
Eur J Vasc allocation concealment Exclusion: primary varicosities involving to a level es
Surg 2006; 31: likely initially, but less both the GSV and SSV; prev. var. Veins just below injected Adverse
93-100. likely as study goes on surgery or sclerotherapy; history of DVT the knee. with 6mL events
(see notes for Liu et al. or risk factors for DVT; Coagulopathy; General of a 3%
2011). No mention of PVD; relevant allergies; malignancy; anaesthet STD
blinding. pregnancy. ic used. sclerosant
Treatment
(foam),
Baseline characteristics: failure
188
then
compressi
Stripping Sclero
Multiple
on
phlebecto
applied
Age 20-76 21-72 mies also
using
performe
Female 60% 47% foam
d.
pads and
C2 8/28 11/30
a class II
C3 14/28 8/30 compressi
Compress on
C4 6/28 7/30 ion stocking
bandages for 2
C5 1/28 3/30
applied weeks.
C6 1/28 1/30 post op
and then
VCSS 2-16 2-13
Source

replaced
by a class Randomis
1 elastic ed n=30;
stocking All
for 3 received
weeks. treatment
. 30
attended
3 week
Randomis follow-up.
ed n=30; 1 lost to 3
2 did not month
receive follow-up
treatment
at all (1
189
moved, 1
moved
out of
area). 28
attended
3 week
assessme
nt. 5 lost
to 3
month
assessme
nt (no
reasons
given).
Results:
Stripping surgery (n=28) Foam sclerotherapy (n=30)

Source

HRQoL – AVVS [median pre:26.1 pre:15.4
post:14.1 post:9.3
VCSS [median (range)] 3(0-4) 1(0-5)
CEAP [median (range)] 1(0-5) 1(0-5)
Adverse events (time not stated)
DVT 0/28 0/30
PE 0/28 0/30
phlebitis 0/28 3/30

190
skin pigmentation 1/28 2/30
neural injury 2/28 0/30
Author's conclusions: US guided sclerotherapy combined with sapheno-femoral ligation was less expensive, involved a shorter treatment time and resulted in more
rapid recovery. .
1
2
1 Table 60: Figueiredo 200997
Source
No. of Intervent Comparis Length of Outcome of
Reference Study type patients Patient characteristics ion on follow-up measures funding
Figuerido M, RCT. Allocation decided 60 Patients attending an angiology and Saphenof Injections 1,2 and 6 VCCS None
Araujo S, by random drawing of patients vascular surgery outpatient clinic. emoral or in months
Barros N, papers from a box. With saphenop standing. post
Miranda F. this form of Inclusion: No previous treatment of opliteal Injections interventi
varicose veins; age 18-70; C5; Adverse
Results of randomisation, allocation ligation of foam on.
events
surgical concealment likely combined made into
Exclusion: History of DVT,
treatment initially, but less likely as with the
thrombophilia, allergy to polidocanol,
compared study went on (see notes saphenou saphenou
bronchial asthma, post-thrombotic
with for Liu et al. 2011). No s stripping s trunk. treatment
syndrome; severe systemic disease;
ultrasound- mention of blinding. and Accessory failure
immobility; pregnancy; peripheral
guided foam phlebecto veins
arterial insufficiency; ABI<0.8); LL
sclerotherapy my for cannulate
oedema; diabetic foot; patent foramen
in patients varicose d using 25
ovale on echocardiography.
191
with varicose saphenou gauge

veins: a Baseline characteristics: s butterfly
prospective tributarie needles.
randomised Stripping Sclerotherapy s and Foam was
study. Eur J ligation of polidocan
Age 49(29- 53(25-76)
Vasc Surg 72) incompet ol and air
2009; ent in a ratio
M:F 21:79 15:85 perforatin of 1:4.
g veins. The GSV
pre pain 1.97(0.1 1.81(0.4)
score 9) All received
surgery 8-10 ml
pre oedema 1.66(0.4 1.70(0.47) done in with a
score 8)
one polidocan
pre 1.55(0.6 1.67(0.68) session. ol
inflammation 3) Regional concentra
score anaesthes tion of
ia used. 3%, the
Inelastic small
Source

bandages saphenou
2 days s vein 5ml
post op at a
and then concentra
30-40 tion of 1
mmHg or 3%, the
below accessory
knee veins 5ml
compressi at a
on for 2 concentra
months. tion of 1%
and
perforatin
g veins 1-
30
2 ml at a
192
randomis
concentra
ed.
tion of
Unclear
1%. Foam
how
progress
many
along
received
veins
surgery,
imaged
but 1 lost
with US.
to follow-
Maximum
up
bolus of
(reasons
10ml in
not given)
one
session.
Sessions
repeated
as needed
every 30
days up to
Source

a
maximum
of 3
(average
sessions
per
patient
were 2.1).
After 15
mins of
compressi
on of the
SFJ or
SSV, the
limb
193
bandaged
using an
inelastic
bandage
for 3-5
days.
Then 30-
40 mmHg
below
knee
compressi
on for 3
months.
30
randomis
ed.
Unclear
Source

how
many
received
surgery,
but 3 lost
to follow-
up
(reasons
not given)
Results: mean (sd)
Stripping surgery (n=29) Foam sclerotherapy (n=27)

VCSS pain 30 days 0.93(0.53) 0.89(0.51)
VCSSpain 60 days 0.79(0.49) 0.59(0.50)
194
VCSS pain 180 days 0.72(0.53) 0.56(0.51)

VCSS oedema 30 days 0.69(0.60) 0.70(0.54)
VCSS oedema 60 days 0.59(0.63) 0.56(0.64)
VCSS oedema180 days 0.55(0.63) 0.48(0.64)
VCSS inflammation 30 days 0.76(0.44) 0.89(0.32)
VCSS inflammation 60 days 0.72(0.45) 0.89(0.32)
VCSS inflammation180 days 0.72(0.45) 0.89(0.32)
Adverse events
neurological (subjective) 6/29 0/27
Reflux/recanalisation 3/29 6/27
Author conclusions: US guided foam sclerotherapy is a safe and effective option for patients with chronic venous disorders.
1
2
1 Table 61: Kalodiki 201112921

Kalodiki E, RCT. 73 Inclusion: Patients with primary Conventio Foam 3 weeks, HRQoL – None
Lattimer C, patients symptomatic varicosities involving the nal high sclerother 3,6 and SF36 and
Azzam M, Patients selected by (82 legs). GSV, without previous treatment and DFL apy with 12 AVVs.
Shawish E, drawing sealed suitable for day case surgery. stripping 6mL of months
Bountouroglo envelopes. For impact of surgery 3% and
u D, this on likelihood of Exclusion: Primary varicosities involving combined Sodium yearly
adequate allocation the GSV and saphenous vein (???), Physician
Geroulakos G. with tetra thereafter
concealment please see previous surgery or sclerotherapy for reported
Long term multiple decyl . Median
notes on Liu et al. 2011. varicosities, past DVT, Coagulopathy, disease
results of a phlebecto sulphate follow-up
Initially only the most PVD, relevant allergies, malignancy or severity –
randomised mies (STS) (1.2 was 5
symptomatic leg was pregnancy. CEAP, VCSS,
controlled using mL of STS years.
randomised in bilateral VSDS.
trial on Muller mixed
patients. However if Baseline characteristics: Median (IQR)
ultrasound- hooks. with 4.8
guided foam varicose veins developed Stripping Sclerotherapy General mL of air)
195
sclerotherapy in the contralateral limb anaesthes injected Adverse

combined this was included and Age 49(29-72) 53(25-76) ia used. directly events
with given the same Immediat into the
M:F 21:79 15:85
saphenofemor randomisation. ely post- vein
al ligation vs. C2 19/43 18/39 op under US
Reflux
standard compressi guidance.
C3 11/43 10/39
surgery for ve Post
varicose veins. C4 11/43 7/39 bandages procedur
Journal of applied, e a 18-24
vascular C5 1/43 3/39 which mmHg
surgery; 2011 C6 1/43 1/39 were thigh high
(in press). changed graduated
VCSS 5(3-12) 4.5(2-15) for a elastic
NB This article compressi compressi
in press has VSDS 1 (IQR 1 (IQR unclear)
unclear) ve on
many typos stocking stocking
and errors. AVVQ 16.32 12.28 (IQR before was
(IQR unclear)

unclear) discharge applied.
from the Patients
SF-36 No report
on day ward. worse this
similarity. for 2
No data weeks
given but
continuou
appear n=43
very sly, and
limbs (39
similar on then 1
figure
subjects)
week in
the day
only for
another
week.
Patients
also told
to walk
196
for 2
miles / 2
hours
daily
n=39
limbs (34
subjects)
Results: Median (IQR) given.
Stripping surgery (n=43 legs) Foam sclerotherapy (n=39 legs) p
AVVQ at 3 years 8.94 (IQR unclear) 4.97(IQR unclear) NS??
AVVQ at 5 years 5.45(IQR unclear) 7.345(IQR unclear) 0.015
SF-36 Data only given in figures, and p values

only given in text. Reported that no

difference between groups in changes
on the physical(p=0.724) and mental
scores(p=0.354)
VCSS increase from baseline to 3 1(0-9) 1(0-9) 0.504

years
very unclearly reported very unclearly reported
VCSS increase from baseline to 5
years
VCSS absolute score at 3 years reported no diff between groups 0.313
VCSS absolute score at 3 years reported no diff between groups 0.104
VSDS at 3 years 0.5(IQR unclear) 1.0(IQR unclear) 0.780
VSDS at 5 years 1.0(IQR unclear) 0.25(IQR unclear) 0.388

197
Adverse events
thromoboembolism (DVT and PE) 0/43 0/39
major neurologic event (i.e. stroke) 0/43 0/39
thrombophlebitis 0/43 3/39
saphenous nerve injury 2/43 0/39
hematoma 1/43 0/39
skin ulcer 1/43 0/39
Reflux at 3 years ABOVE KNEE* 7/26 11/33
Reflux at 5 years ABOVE KNEE 9/26 13/33

Reflux at 3 years BELOW KNEE 14/26 19/33
Reflux at 5 years BELOW KNEE 9/26 14/33
*cannot sum above and below knee data as some may be from the same subjects
Author's conclusions: At 3 and 5 years of follow-up, the treatment was equally effective in the surgical and foam groups, as demonstrated with VCSS, VSDS and the SF-
36...at 5 years the AVVQ was significantly better in the surgical group.
1
2
198
1 Table 62: Liu2011148
Length
of Source
No of follow- Outcome of
Reference Study type patients Patient characteristics Intervention Comparison up measures funding
Liu X, Jia X, RCT; China. 60 Patients undergoing treatment N=30 N=29 3 months AVVQ None
Guo W, patients for varicose veins in a vascular and 6
Xiong H, Allocations placed randomis surgery clinic; 26 men and 34 Stripping surgery, Ultrasound-guided months
Zhang M, Liu in 60 sealed ed; 59 women; CEAP ranged from C2-C6 using a flexible foam obliteration post-op.
envelopes and then intraluminal of the GSV. After Physician
X, Du X, treated. (no breakdown given). Median
shuffled. Each stripper to strip SFJ ligation, 6mL reported
Zhang MH. age 49 (range 37-66).
Ultrasound- recruited patient from groin to knee. sclerosing foam (1
guided foam given one. Not Inclusion: symptomatic primary Preceded by flush part of 1%
sclerotherap stated if there was varicose veins with primary SFJ ligation, division of Lauromacrogol Adverse
y of the any patient and GSV reflux, as shown by tributaries. [Polidocanol] and 4 events
great blinding. Also no duplex (reflux duration >0.5 secs Varicosities also parts of air)
saphenous mention of after calf compression-release treated by injected into GSV
199
vein with assessor blinding. manoeuvres). phlebectomy. Done proximal cut end
Although the under GA. All via 10mL syringe treatment
sapheno-
method of Exclusion: None given patients with connected to a 21 failure
femoral
ligation allocation meant residual varicose gauge butterfly.
compared to that group veins in both Sclerosant foam
Demographics not given. No
standard allocation was groups received flow monitored via
breakdown of any characteristics
stripping: a automatically additional foam US. Remnant trunks
done by group. However, groups
prospective concealed from the sclerotherapy as not filled with foam
matched for CEAP median
clinical recruiter at first, it outpatients (not were punctured
(range): both 4(2-6). AVVQ
study. is possible that stated when). and filled with
median (range) was similar:
International towards the end of additional
Sclerotherapy: 15(11-26);
Angiology recruitment it sclerosant. Done
surgery: 19(14-29).
2011; 30: might become under GA . All
30 randomised; 29
321-6. possible to predict patients with
received treatment
the allocation of residual varicose
(patient changed
the next patient to veins in both
mind); 1 loss to
be recruited (i.e. if groups received
follow-up at 3
after 50 patients it additional foam
months (didn’t
Length
of Source
was known that attend follow-up); sclerotherapy as
28/30 stripping No further loss to outpatients (not
places had been follow-up at 6 stated when).
already taken up, months.
then it would be
known that the
30 randomised; 29
probability of the
received treatment;
next patient being a
2 loss to follow-up
control patient
at 3 months (didn’t
would be 80%).
attend follow-up); 2
further patients
lost to follow-up at
6 months (didn’t
200
attend follow-up).
Results:
Stripping surgery (n=30) Foam sclerotherapy (n=29) p
HRQL
AVVQ median (range) 3 months 12(8-17) 9(5-16) no intergroup p value given
Physician reported outcomes
CEAP median (range) 3 months 1(0-4) 1(0-3) no intergroup p value given
Adverse events
groin hematoma 1/30 0/29
neural injury 2/30 0/29

Length
of Source
DVT 0/30 0/29
PE 0/30 0/29
Post op use of analgesia (any) 24/30 8/29
No full obliteration 3 months (requiring second 3/28 3/28

session of sclero)
No full obliteration 6 months (requiring second 3/26 5/25

201
session of sclero)
Author conclusions: US guided sclerotherapy, combined with sapheno-femoral ligation involved a shorter treatment time, less post-operative discomfort and resulted
in more rapid recovery compared to conventional GSV stripping.
1
1 Table 63: Rasmussen 2011221
Foam Source
No of Stripping sclerotherap Endotherm Length of Outcome of
Reference Study type patients Patient characteristics surgery y al ablation follow-up measures funding
Rasmussen RCT, 500 Inclusion: 18-75 years; symptomatic N=125 N=125 (145 N=250 (292 3 days, 1 Quality of Public
LH, Denmark. patients varicose veins; CEAP 2-4; Great (143 legs). legs) legs) month, 1 life: SF36 health
Lawaetz M, were Saphenous Vein(GSV) incompetence, year. score and Insuranc
Bjoern L, 2 private randomise defined by reflux >0.5secs on duplex; Flush Ultrasound- Endovenou AVVQ. e
Vennits B, surgical d Bilateral treatment allowed so long as ligation of guided foam s Laser It was Research
Blemings A, centres. in same group. Patients with the GSV sclerotherapy ablation intended Physician- Foundati
and Eklof B. 125 in recurrent varicose veins also included and [UGFS] (in (EVLA): to reported on of
Randomisatio each division of the reversed Under continue outcomes:
Randomize if GSV preserved to the groin. Denmark
n in blocks, group. The all Trendelenbur duplex follow-up VCSS.
d clinical
but method results for Exclusion: Duplication of the tributaries g position); guidance yearly for
trial
not clearly endotherm saphenous trunk or an incompetent . Use of a 3% with 980nm 5 years. Treatment
comparing
described. al laser anterior accessory saphenous vein; PIN polidocanol diode laser failure:
endovenou
Allocation ablation small saphenous vein reflux; previous stripper to (Aethoxyscler
st
for 1 17 defined as a
s laser
concealment patent GSV
202
ablation, (n=125) DVT; history of arterial insufficiency: strip GSV ol®); 2ml pts and
adequate via and radio brachial pressure index <0.9, or both; to just solution then 1470 with reflux,
radiofrequ
sealed frequency axial deep vein insufficiency; tortuous below the mixed with diode laser or GSV not
ency
envelopes. ablation GSV. knee. 8ml air. for the rest. stripped
ablation,
(n=125) Retreatment Pulse mode successfully
foam No blinding
have been Baseline characteristics: mean Common allowed was used in
sclerothera reported. Recurrence
combined (range). Authors report that groups procedure within 1 one centre
py and rates
in these well-matched. s: month. but
surgical
results. Phlebecto continuous
stripping Stripp UGF Endoth Adverse
mies to Common used in the
for great ing S ermal events
All remove procedures: other.
saphenous surge (RF and (including
received varicositie Phlebectomie Cannulation
varicose ry EVLA ) complicatio
interventio s in all s to remove just below
veins. ns e.g. DVT
n except groups. varicosities in the knee.
British N subjects 124 124 250 and PE,
one Compressi all groups. The laser
Journal of post-
patient n legs 142 144 292 on applied Compression fibre was
Surgery interventio
(and 1 leg) post applied via a advanced
2011; n superficial
in the Age 50 51 51 operativel 30 mmHg
Foam Source

98:1079– stripping (19- (18- (18-75) y for all – stocking for 2 until 2cm phlebitis,
1087. and foam 72) 75) at 20 weeks. Note below the post-
sclerother mmHg for that this sapheno- interventio
apy %Female 77 76 77 2 weeks. group was femoral n pain
groups, given a junction, during first
due to CEAP2-3 97 96 97 different and then 10 days)
dizziness (legs) compression the GSV
(stripping strength to was ablated Time to
CEAP 4-6 3 4 3 resume/ret
group) and (legs) the other two during
patient’s groups. withdrawal. urn to
wishes normal
Previous 8 4 8
(sclerother Endovenou activities
surgery
apy s and work
group). GSV (diam ) 7.8 8.7 7.8 (3- radiofreque
(mm) (3-14) (3- 14) ncy
203
At 1 year 20) ablation

n=17 (21 (EVRF):
legs) lost Number of 15 (1- 15 15 (1- catheter
to follow- phlebecto 48) (1- 48) advanced
up or not mies 43) under US
seen in the guidance to
sclerother surgeon’s 32 19 32 (15- 2cm below
apy group, time (min) (15- (5- 80) the
37 (47 80) 145 sapheno-
legs) in the ) femoral
endotherm junction.
al group Then
and n=27 withdrawn,
(34 legs) in with
the temperatur
stripping es
group. maintained
at 120
Foam Source

degrees for
20 seconds
per
segment via
a
thermostat.
Common
procedures:
Phlebectom
ies to
remove
varicosities
in all
groups.
204
Compressio
n applied
post
operatively
for all – at
20 mmHg
Results
Stripping surgery Foam Sclerotherapy Endovenous Laser Ablation Radiofrequency ablation
(n=124 patients) (n=124 patients) (n=125) ( n=125)
Treatment failure at 3 4/141 legs 3/143 legs 0/143 0/146
a
days
Treatment failure at 1 3/135 legs 2/144 legs 1/144 0/141
month
Recurrent varicose veins 16/108 17/123 7/121 6/124
at 1 year
Foam Source

st
Adverse events during 1 month

Major:
DVT (requiring treatment) 1/135 1/144 0/144 0/141
PE (requiring treatment) 0/135 1/144 0/144 0/141
Minor:
Phlebitis 5/135 17/144 4/144 12/141
Infection 1/135 4/144 0/144 1/141
Paraesthesia 5/13 2/144 3/144 6/141
hyper pigmentation 6/135 8/144 3/144 8/141
Haemorrhage 1/135 1/144 1/144 0/141
205
Pain scores in first 10 days 2.25 (2.23) 1.60 (2.04) 1.21 (1.72) 2.25 (2.23)
[mean(sd)] [VAS, 0-10, 10
worst]
SF-36 score (mean [SD]) at 1yr

Physical functioning 92.82 (13.35) 91.33 (14.93) 92.02 (11.61) 92.22(12.62)
Role physical 93.41(16.32) 90.36 (20.56) 93.51(14.78) 94.65(10.64)
Bodily pain 88.77(17.11) 85.11(23.45) 88.43(19.55) 89.92(16.85)
General health 66.02 (14.00) 63.36 (18.31) 64.90(11.99) 67.08(11.82)
Vitality 76.99 (15.54) 73.20 (22.67) 77.74(14.03) 76(17.51)
Social functioning 95.19 (11.60) 93.10 (16.51) 96.51(11.22) 97.11(14.45)
Role – emotional 94.20 (14.02) 91.92 (17.11) 95.95(10.15) 94.5(11.02)
Mental health 85.92 (12.18) 84.58 (15.77) 87.70(10.51) 87.08(11.94)
Foam Source

Summary Scores
PHYSICAL 4 weeks 48.14(7.21) 49.2(7.56) 47.68(6.95) 49.88(7)
PHYSICAL 1 year 53.33(5.9) 51.94(7.66) 52.62(5.98) 53.23(5.32)
MENTAL 4 weeks 55.15(7.81) 56.1(7.51) 55.55(8.21) 55.57(7.38)
MENTAL 1 year 55.83(6.31) 54.73(8.89) 56.74(5.44) 56.52(6.17)
VCSS NOTE that only graphs were presented, and no actual data were provided.
AVVSSS NOTE that only graphs were presented, and no actual data were provided.
Time to return to normal 4 (0-30) 1 (0-30) 2(0-25) 1(0-30)
activities (days)
median(range)
Time to return to work 4.3 (0-42) 2.9 (0-33) 3.6(0-46) 2.9(0-14)
(days) median (range)
206
1 (a) Failure defined as patent GSV with reflux OR GSV not stripped successfully (unfair comparison as unstrapped GSV does not equal incompetent GSV, whereas unblocked GSV has to occur
2 with reflux.
1 Table 64: Shadid2012244

Shadid N, Multicentre 460 Patients with primary GSV Stripping Foam 2 years Recurrence None
Ceulen R, randomised randomised incompetence. All had C2-5EpAsPr surgery. sclerother (clinical stated
Nelemans P. controlled trial. (233 to foam Day case apy. 3% symptoms
et al. Computer generated and 227 to Inclusion: presence of 1 or more under GA policodan plus reflux)
Randomised randomisation with surgery). symptoms in combination with or spinal. ol in a at 2 years
clinical trial of permuted blocks of incompetence of the SFJ and GSV, with Ligation foam (1:4
ultrasound- eight. 3 did not reflux time of >0.5 sec; normal deep of SFJ and ratio of Reflux
guided foam receive foam venous system GSV sclerosant (regardless
sclerotherapy (2 declined divided to air). of
and 1 not Exclusion: active ulceration; symptoms)
versus surgery and Class II
feasible) and contraindications to use of policodanol at 2 years
for the stripped elastic
incompetent 27 did not to just stockings
Baseline characteristics: Similar in both EQ-5D
great receive below worn for
groups
saphenous surgery (24 knee. 6 weeks. Symptoms
207
vein. declined, 1 Foam Surgery Phlebecto

CVA, 1 mies NO Adverse
surgeon not Age 51.6(13.3) 50.7(13.4) CROSSECT
done as events
co-operating, F:M 173:57 141:59 needed. OMY
1 pregnancy). Class II
C2 86.5% 80%
elastic
17 lost to
C3 9.1% 11.5% stockings
follow-up in
worn for
Foam; 23 lost C4 9.1% 8% 6 weeks.
to follow-up in
stripping. C5 2.2% 3%
Resaons did
not appear to
be related to
outcome.
Results:
Stripping surgery Foam sclerotherapy

Clinical recurrence (symptoms with accompanying 16/177 24/213
reflux)at 2 years
Clinical recurrence (symptoms with accompanying 13.8% 11.9%
reflux)at 1year
Clinical recurrence (symptoms with accompanying 8.56% 10.8%
reflux)at 3 months
Reflux at 2 years 18.2% 21.3%
Reflux at 1year 23.1% 29.16%
Reflux at 3 months 18.2% 21.3%
Change in VCSS from baseline at 2 years -1.75 (2.135) -1.49 (2.135) P=0.232 (no variances reported but common
208
sd for each calculated as: 2.135)

Mean change in EQ-5D from baseline at 2 years 0.061 (0.211) 0.064 (0.211) P=0.889 (no variances reported but common
sd for each calculated as: 0.211)
More pain at 2 years 6/177 14/213
More tired/heavy feeling at 2 years 5/177 6/213
More cramps at 2 years 8/177 8/213
More restless legs at 2 years 21/177 29/213
Patient not satisfied – aesthetic at 2 years 23/177 31/213
Patient not satisfied – functional at 2 years 17/177 17/213
More pain at 1 year 14/188 20/221
More tired/heavy feeling at 1 year 9/188 5/221
More cramps at 1 year 9/188 10/221
More restless legs at 1 year 26/188 34/221
Patient not satisfied – aesthetic at 1 year 32/188 33/221

Patient not satisfied – functional at 1 year 28/188 22/221
More pain at 3 months 10/176 12/217
More tired/heavy feeling at 3 months 2/176 8/217
More cramps at 3 months 6/176 9/217
More restless legs at 3 months 16/176 27/217
Patient not satisfied – aesthetic at 3 months 19/176 39/217
Patient not satisfied – functional at 3 months 15/176 20/217
Mean change of EQ-%D “health state” from baseline -1.8(25.4) -0.36(25.4) P=0.577 (no variances reported but common
to 2 years sd for each calculated as: 25.4)
Complete satisfaction with reduction in venous 117/177 127/213
complaints at 2 years
Need for >1 treatment 10/200 40/230
[2 for re-surgery, 8 for [35 one extra session of foam, 5
209
foam] >1 extra session]

Adverse events (within 1 week)
Groin infection 4/200 0/230
Haematoma 3/200 0/230
Parasthesia 6/200 0/230
Pain at injection site 0/200 6/230
Thrombophlebitis 0/200 17/230
Headache/migraine 0/200 3/230
DVT 0/200 1/230
PE 0/200 1/230
Later adverse events (at 2 yrs)
Hyper-pigmentation 2/200 12/230
Telangiectatic matting 2/200 6/230
1
1 Table 65: Wright2006286
No. of Patient characteristics Interventi Comparis Length of Outcome Source of

Reference Study type patients on on follow-up measures funding
Wright D, RCT, open-label, 2 cohorts Inclusion: Male or female aged 18-75 N=94 N=178 Days 7 Post- Acknowl
Gobin JP, international, but only years with moderate-to-severe varicose patients patients and 28, procedure edgemen
Bradbury AW, multicentre. looking at veins (C2-C4); SFJ or SPJ junction treated treated and at pain at Day 6 t of
Coleridge- the incompetence or both with retrograde with with months 3 (Visual Sigvaris
Smith P, Varisolve blood flow for >1s and <7s ®
and 12. Analogue Ltd for
Spoelstra H, cohort/ demonstrated by duplex scanning; great Surgery: Varisolve Scale (VAS) the
Randomisation not high polidocan
Berridge D, surgery saphenous incompetence and/or short 1-100mm provision
described. Allocation ligation ol
Wittens CHA, (n=311); saphenous incompetence; minimum of scale) of
concealment unclear. performe microfoa
Sommer A, 210 10cm proximal trunk vein compress
Nelzen O, and patients incompetence; normal deep venous d in m; a ion
Chanter D. randomis system on duplex scanning, no evidence 91.5% of uniform stockings
patients, foam of Response
Varisolve No blinding. ed to of occlusion or incompetence. Evidence , but
stripping physicolo defined as:
polidocanol Varisolve of reflux was acceptable. none
in 88.3% gic gases, occlusion (or
microfoam and 101 declared
210
Exclusion: C5 and C6 excluded; history and principally for surgery,

compared randomis for the
of major superficial thrombophlebitis; avulsion oxygen absence) of
with surgery ed to provision
venographic or ultrasonographic phlebeco and the treated
or surgery. of
evidence of current or previous DVT; my in carbon vein AND
sclerotherapy Varisolve
immobility; BMI >32kg/m ;
2
53.2%. dioxide, elimination
in the .
contraindications for polidocanol combined of junctional
management
Withdrew including severe hypertension, diabetes, with a 1% reflux.
of varicose
from asthma and advance arteriosclerosis. aqueous
veins in the
study solution
presence of
after Baseline characteristics: of
trunk vein Adverse
treatment polidocan
incompetence Surgery Varisolve events:
: 32 ol.
: European foam common
patients Maximal
randomized (n=94) sclerotherapy treatment-
from dose
controlled (n=178) related
Varisolve initially
trial. adverse
group and set at
Phlebology Mean 49±11.2 49.9±12.6 events (i.e.
7 from 60mL and
2006;21:180 – age ±SD contusion,
the subseque
190. (years) skin
Patient characteristics

surgery ntly discolouratio
group. M:F 34:60 66:112 reduced n, pain in
to 30mL. limb,
CEAP C3 11 (11.7%) 14 (7.9%)
The headache
CEAP C4 10 (10.6%) 20 (11.2%) Varisolve and
technique haematoma)
Primary VV carried and serious
out under adverse
GSV 77 (81.9%) 141 (79.2%) ultrasoun events (i.e.
d DVT, PE)
SSV 8 (8.5%) 12 (6.7%) guidance.
30-
GSV+SSV 0 8 (4.5%)
40mmHg
Recurrent VV thigh
length
GSV 6 (6.4%) 11 (6.2%) compressi
211
on
SSV 2 (2.1%) 1 (0.6%) stocking
worn 14
GSV+SSV 1 (1.7%) 3 (1.7%) days post
treatment
.
Results:
Surgery (n=94) Varisolve foam sclerotherapy (n=178) p

Response (i.e. occlusion of trunk vein and elimination of reflux)
at 3 months 82/94 (87.2%) 120/176 (68.2%)
at 12 months 81/94 (86.2%) 111/176 (63.1%)
Post-procedure pain at Day 9 2 <0.001

6 (Median score on a
Patient characteristics

100mm VAS scale)
Most common treatment-related adverse events

Contusion 80 (85.1%) 122 (68.5%) -
Skin discolouration (= hyper 39 (41.5%) 98 (55.1%) -
pigmentation)
Pain in limb 39 (41.5%) 73 (41%) -
Headache 20 (21.3%) 41 (23%) -
Haematoma 1 (1.1%) 11 (6.2%) -
Serious adverse events

Deep vein thrombosis 0 9 (4.5%) -
Pulmonary embolism 0 0 -
212
Author's conclusions: Varisolve was non-inferior to alternative treatment. Surgery was more efficacious, but Varisolve caused less pain. The Varisolve technique is a
useful additional treatment for varicose veins and trunk vein incompetence.
1
1 G.5.2 Stripping surgery vs. endothermal ablation
2 Table 66: Carradice201147
Carradice D, RCT. Non 280 Inclusion: patients with primary Stripping surgery. EVLA. GSV 1 week, 6 SF-36 None
Mekako AI, blinded. randomised symptomatic unilateral varicose Flush SFJ ligation cannulated weeks, 3
Mazari FAK, “Randomisation” (140 from veins, with isolated SFJ followed by at the months EuroQoL 5D
Samuel N, through choice each group). incompetence, and reflux in the ligation of all lowest point and 1
AVVQ
Hatfield J and of sealed In GSV. Incompetence defined as tributaries to the of reflux. year.
nd
Chetter IC. envelopes by the endovenous reflux of at least 1 sec on 2 branch, then EVLA at CEAP
Randomised patient. This laser Doppler. inversion stripping 810nm
clinical trial method, though ablation of the GSV to the wavelength VCSS
of unorthodox, (EVLA) Exclusion: previous treatment knee. GA used. and power
endovenous ensures group, 1 did for ipsilateral varicose veins, 14W applied
laser ablation allocation not receive deep vein incompetence or Common during
post-op pain
213
compared concealment intervention; obstruction, age < 18 years, procedures: Multi- withdrawal.
with provided all in surgery pregnancy, impalpable foot phlebectomies LA used.
conventional envelopes are group, 3 did pulses. given to both
surgery for identical and not receive groups as needed. Satisfaction
Baseline characteristics: Only
great have been intervention with cosmetic
significant difference was for
saphenous properly (all result.
SF36 mental health (p=0.03).
varicose shuffled. withdrew
Continuous vars all mean (sd)
veins. British However, from trial).
unless stated. * median (IQR)
Journal of towards the end Over one
Surgery of the trial, it year, in EVLA
2011A; 98: may become group 24
501-510. easier to guess lost to
to which group follow-up EVLA Surgery
recruited subject and in Age 49 (14) 49 (13)
will be allocated, surgery
if it is known group 15 M:F 54:85 47:90
that there has lost to
ex smoker 35/132 37/130
been an follow-up.
current 35/132 30/130
imbalance of smoker
allocations up to
that point. In BMI 26.6 (5.0) 26.0 (4.3)
that sense, the
GSV diam 8.7 (2.7) 8.2 (2.7)
risk of allocation (groin) mm
concealment
breaking down is VCSS* 4 (3-5) 4 (3-5)
possible.
CEAP 2 95/138 96/137
CEAP 3-6 43/138 41/137
AVVQ* 12.6 (9.6- 13.7 (9.9-

17.2) 18.2)
SF36*
214
physical 90 (75- 90 (80-100)

functioning 100)
role 100 (50- 100 (75-100)

physical 100)
bodily pain 74 (52- 74 (52-100)

100)
gen health 77 (62- 77 (67-87)

92)
Vitality 70 (55- 70 (53-80)

80)
social 100 (75-

functioning 100)
role 100 100

emotional
mental 84 (68- 80 (68-90)

health 92)
EQ5d* 0.848 0.841 (0.796-

(0.796- 1)
1.00)
SF6D* 0.804 0.795 (0.717-

(0.744- 0.847)
0.856)
Results:
EVLA Surgery p
Health related QoL (SF36) Higher score is better outcome). Median (IQR)
physical functioning -1week 88 (70-95) 80(65-90) 0.012
role physical -1week 100 (25-100) 50(0-100) 0.005
bodily pain -1week 74(54-84) 62(41-74) 0.031
215
gen health -1week 81(67-92) 82(72-92) NS

vitality -1week 70(60-80) 65(55-800 0.049
social functioning -1week 100 (75-100) 75(63-100) 0.004
role emotional -1week 100 100(67-100) 0.027
mental health -1week 88(76-92) 84(68-92) NS
physical functioning -1year 95(85-100) 95(80-100)
role physical -1year 100 100 NS
bodily pain -1year 100(72-100) 94(72-100) NS
gen health -1year 82(67-92) 82(72-92) NS
vitality -1year 75(60-85) 75(65-85) NS
social functioning -1year 100(88-100) 100(75-100) NS
role emotional -1year 100 100 NS
mental health -1year 88(74-92) 88(76-92) NS
AVVQ 1 week 16.6 (12.4-21.1) 16.5(12.2-22.7) NS
AVVQ 1 year 2.0(0-5.3) 2.0(0-5.3) NS
EQ5D - 1 week 0.796(0.760-1) 0.801(0.691-0.895) NS
EQ5D – 1 year 1(0.877-1) 1(0.841-1) NS
SF-5D – 1 week 0.796(0.735-0.838) 0.759(0.672-0.830) 0.003
SF-5D – 1 year 0.843(0.773-0.876) 0.835(0.777-0.878) NS
pain at day 1 less pain from day 1 to day 6 in EVLA gp (p=0.004 to <0.001). But no
data given except in low resolution figure.
VCSS at 1 year 1(0-1) 1(0-1) NS
Adverse events
sensory disturbance 4/137 13/133 0.020
haematoma 1/137 11/133 0.003
infection 2/137 8/133 0.048
216
phlebitis 4/137 6/133 0.536

persistent pain 1/137 5/133 0.116
pigmentation 4/137 1/133 0.371
anaesthetic complication 0/137 3/133 0.118
persistent bruising 1/137 2/133 0.618
allergy 0/137 1/133 0.493
thromboembolism 0/137 0/133 1
Cosmetic satisfaction at 1 year EVLA higher satisfaction (p=0.034) but no data given.
Overall satisfaction at 1 year No difference between groups for overall satisfaction (NS) but no data given in paper.
1
2
1 Table 67: Carradice2011A48
Carradice D, This is the None Carradice D, Mekako AI, Mazari This is the same None Carradice This is the same None
Mekako AI, same study as FAK, Samuel N, Hatfield J, Chetter study as Carradice D, Mekako study as
Mazari FAK, Carradice IC. Clinical and technical 2011A, with some AI, Mazari Carradice
Samuel N, 2011A, with outcomes from a randomised additional FAK, 2011A, with
Hatfield J, some clinical trial of endovenous laser outcomes. See Samuel N, some additional
Chetter IC. additional ablation compared with Carradice 20011A Hatfield J, outcomes. See
Clinical and outcomes. See conventional surgery for great Chetter IC. Carradice
technical Carradice saphenous varicose veins. British Clinical 20011A
outcomes 20011A Journal of Surgery 2011; 98: and
from a 1117-1123. technical
randomised outcomes
clinical trial from a
of randomise
endovenous d clinical
217
laser ablation trial of

compared endoveno
with us laser
conventional ablation
surgery for compared
great with
saphenous convention
varicose al surgery
veins. British for great
Journal of saphenous
Surgery 2011; varicose
98: 1117- veins.
1123. British
Journal of
Surgery
2011; 98:
1117-
1123.
Results
Surgery EVLA p
Initial treatment failure [defined as failure to fully remove the GSV and all groin SFJ 10/132 1/137 0.005
tributaries (Surgery), or flow in competent GSV (EVLA)] – data collected within 6
weeks
Clinical recurrence after 1 year (defined as the development of neovascularisation 23/113 5/124 0.001
(Surgery) or recanalisation (EVLA), or the development of new segments of
incompetence in superficial veins and perforators.
1
2
218
1 Table 68: Darwood200867
Reference Study type No. of Patient characteristics Intervention Comparison Length of Outcome Source
patients follow-up measures of
fundin
g
Darwood RJ, RCT, UK. 136 legs from Inclusion: >18 years with symptomatic Saphenofemora Endovenous 1, 6, 12 Disease not
Theivacumar N, 118 patients varicose veins and primary l ligation, GSV laser ablation and 52 specific stated
Dellagrammatica Allocation – if bilateral saphenofemoral incompetence stripping to (EVLA) using a weeks QoL
s D, Mavor AID, concealment symptoms, confirmed with duplex US. knee level with 810nm diode post [Aberdeen
Gough MJ. likely through both legs perforation laser source. treatment VV
Randomised the use of were used in Exclusion: taking warfarin, or patient invagination The GSV was . symptom
clinical trial sealed the study, unsuitable for EVLA (twisted GSV, stripper, and cannulated score
comparing envelopes. and each leg large incompetent anterior accessory multiple near the knee (AVVSS)]
endovenous laser Randomisatio was given the saphenous vein) or surgery (co- phlebectomies under US-
ablation with n method same morbidity prohibiting general of varicosities guidance and
surgery for the unclear. treatment. anaesthesia). as a day case LA applied to
Abolition
treatment of This will have under GA. the vein. A 600
219
Baseline characteristics: Medians and of reflux

primary great artificially micron laser
IQR shown. No statistical testing as Prophylactic with
saphenous No ITT used. reduced fibre inserted
sample size calculation target not met heparin given Duplex
varicose veins. variance and drawn
(very sensible as lack of power would pre-surgery. LA imaging
British Journal of within back through
lead to over-confidence in group applied to the
Surgery 2008; 95: groups, but as the vein.
Drop out: equivalence). wound area but
294-301 data were
analysed non- not the GSV Two different Patient
EVLA1:3/49 EVLA1 EVLA2
parametricall tract. laser protocols symptoms
legs were used:
y this will not Age 42 (30.5- 52 935-59) and
Non stretch
EVLA2: 9/42 have 54.5) cosmesis
bandaging used EVLA1: 12W
legs mattered.
F:M ratio 22:16 16:11 for 1 day, power with 1
followed by full sec pulses and
SURGERY:
CEAP2 37/47 24/33 length grade II 1 sec intervals. Patient
11/45 legs
compression Catheter satisfactio
Reasons: CEAP3 4/47 6/33 stocking for 2 withdrawn 2-3 n
unclear weeks. mm on each
CEAP4 2/47 1/33
fundin
g
rest interval.
CEAP5 3/47 0/33 Physician
EVLA2: 14W outcomes
Loss to follow- CEAP 1/47 2/33 power – venous
up (none of unknown continuously clinical
those with constant severity
dropping out VCSS 4 (3-5) 4 (3-5) 2-3 mm/sec score
were followed withdrawal. (VCSS)
up): bilateral 9/47 6/33
Non stretch
EVLA1:5/46 AVVSS 11.76 (9.8- 14.3 (8.9-
compression
legs 19.4) 19.6) Adverse
bandage
applied events,
EVLA2: 4/33 including
postoperativel
220
legs post-
y for 1 week,
followed by a procedure
SURGERY:
grade II pain.
2/34 legs
compression
Reasons stocking for a
unclear further week.
Injection
sclerotherapy
would be
performed at 6
weeks for
residual
varicosities if
requested by
the patient.
This partially
controls for
the
fundin
g
phlebectomies
given to the
surgery group,
but there is
still a
possibility that
the differences
between
sclerotherapy
and
phlebectomies
would have
confounded
221
results.
Results: Median (IQR)
Outcome EVLA1 EVLA2 Surgery p
QoL – AVVSS 3months (score out of 100, with 5.6 (1.45-8.2); n=34 4.2 (1.7-7.9); n=20 5.32 (1.0-7.7); n=26 not stated
100 worst symptoms?)
QoL – AVVSS 12months 1.8 (0.1-5.9); n=22 2.5 (0-5.6); n=15 3.9 (0-10.3); n=9 not stated
QoL – AVVSS improvement from baseline at 9.4 (4.5-14.9) 10.3(5.0-15.0) 8.4 (4.5-13.2) 0.694
3months
Abolition of GSV reflux at 12 weeks 41/42 26/29 28/32 0.227
Abolition of GSV reflux at 52 weeks (includes 24/28 19/21 11/12
only those with abolition at 12 weeks)
Abolition of SFJ reflux at 12 weeks 39/42 27/29 32/32 0.307
Abolition of SFJ reflux at 52 weeks (includes 23/28 19/21 11/12
only those with abolition at 12 weeks)
VCSS 0 (0-1) 0 (0-1) 0 (0-1) NS
fundin
g
Patient satisfaction at 12 weeks (100mm VAS; 95 (81-95) 91 (84-97) 91 (81-95) 0.267
100 = high satisfaction)
Cosmesis at 12 weeks (100mm VAS; 100 = 92 (80-95) 92 (77-95) 93 (76-98) 0.980
high satisfaction)
Adverse events EVLA1 EVLA2 Surgery
Post-operative pain (mean of the first 7 days 11 18 14
medians
symptomatic phlebitis 6/42 3/29 0
paraesthesiae/ numbness 0 1/29 4/32
pruritis at cannulation site 0 1/29 0
upper thigh discolouration/bruising 0 1/29 2/32
222
wound infections requiring antibiotics 0 0 2/32

ARDS, leading to 7 days ventilation in ICU 0 0 1/32
Treatment failure see abolition of reflux results
return to work in one week 29/34 20/24 14/25
1
2
1 Table 69: Elkaffas 2011113
Reference Study type No. of Patient characteristics Intervention Comparison Length Outcome Source
patients of measures of
follow- funding
up
ElKaffas KH, RCT. 180 patients. Inclusion: SFJ and GSV reflux on SF high ligation Radiofrequency 1 week, Treatment None
ElKashef O, Randomisation 90 in EVRF duplex, either on standing manual and GSV ablation (EVRF) 1 month, failure
ElBaz W. Great method was group and compression/release or Valsalver stripping at used. Closure 6
Saphenous where 90 in surgery manoeuvres. ankle (n=40) or system (VNUS months,
Vein patients group. Drop knee (n=50). GA medical 12
Exclusion: Patients with deep or Adverse
Radiofrequency “blindly out data is used for all, all technologies) months
superficial venous thrombosis; events
Ablation versus choose an unclear, as were managed used. two 18
standard assignment 90 are patients on anticoagulants; PAD, as inpatients. operators months,
dtripping in the card that reported to pacemakers, serious systemic Stripping involved. Vein 24
management would put have had disease, pregnancy. Also GSV lumen performed after cannulated at months. Recurrence
of primary them in either treatment in diameter > 18mm in the thigh or very wrapping elastic point of most Mean
varicose veins – group”: this the EVRF twisted veins. bandage to distal reflux and FOLLOW-
223
a randomised has clear group, but reduce tip of RF UP 20.9

Baseline characteristics: surgery
clinical trial. scope for the drop-out postoperative catheter placed (6.8)
group older and with larger GSV
Angiology unconscious data for that haematoma, at least 2cm months.
diameter. All else not significant.
2011; 62: 49-54 bias from the group are with operating distal to the
researcher. reported EVLA Surgery table tilted 30 saphenofemoral
For example, with a deg foot up. junction or just
the card denominator Age 33.1 34.9 distal to the
relating to the of 88. Drop- (2.6) (3.7) superficial
preferred outs over 24 epigastric vein
M:F 42:48 45:45 Common
allocation months orifice. LA used
procedures:
could be were 7 for only. RF
discomfort 69/90 66/90 Both groups had
placed in a the EVRF catheter used
stab
certain group and 9 temperatures of
oedema 36/90 42/90 phlebectomies
position aimed for the 80-85 deg. One
as needed
at encouraging surgery skin changes 12/90 18/90 operator only.
(15/90 in EVRF
its choice. group. No
gp and 39./90 in
Allocation ITT C2 51 45
follow- funding
up
concealment is (imputation) surgery group).
inherent in the was C3 27 27 24/90 also
design, as the reported. needed later
C4 9 12 postoperative
allocation This would
cannot be only be sclerotherapy
C5 3 6 for small veins
known by the relevant to
researcher the Kaplan GSV diameter 7.8 (4.5- 8.6 (4- was needed
until it is made Meir (mm) 12) 14) (none in
by the patient; analysis, [mean(range)] surgery group).
however the which will
problems with hopefully op duration 40 (12) 45 (13)
unconscious have (mins)
bias remain. censored the
224
No evidence of data.
blinding.
Results:
EVLA Surgery p
Treatment failure at completion of intervention (no full occlusion or failure to 6/90 0/90
remove the GSV)
Adverse events (imm. Post op)
focal paresthesia 9/90 3/90
Thrombophlebitis 6/90 0/90
severe pain requiring analgesics 12/90 12/90
hematoma formation 1/90 12/90

iliofemoral DVT 0/90 1/90
severe groin infection 0/90 3/90
follow- funding
up
pulmonary embolism 0/90 0/90
Recurrence over 24 months 12/90 9/90
Average (?median) time to recurrence (Kaplan Meier graph provided but no data 23.3 months (95%CI: 22.5-24.1) 23.0 months (95%CI: 0.4
given) 21.3-24.6)
return to normal activity 3 (3) 7 (2.6)
1
2
225
1 Table 70: Flessenkamper 201299
Reference Study type No. of Patient characteristics Intervention Comparison Lengt Outcome Source
patients h of measure of
follow s fundin
-up g
Flessenkamper I, Hartmann RCT. Three 301 Inclusion: 18-72 years; clinical signs or High ligation 980nm laser 2 AEs Germa
M, Stenger D, Roll S. arm RCT, but randomised symptoms of superficial venous of the SFJ (EVLA) at month n
Endovenous laser ablation one arm not to the 2 arms insufficiency with proven reflux into and 30W in s GSV society
with and without high included in under GSV; life expectancy > 5 years; stripping continuous reflux of
ligation compared with high this review consideration using mode. phlebol
ligation and stripping in the (EVLA with . No attrition Exclusion: previous surgery of the GSV. invagination Performed ogy
treatment of great high ligation) at 2 months technique. under
All had insufficient terminal valve,
saphenous varicose veins: as it is not follow-up Open duplex
diameter of the GSV 5cm distal from
initial results of a “standard” surgery. guidance.
the junction was <16mm.
multicentre randomised treatment. Anaesthetic Tumescent
controlled trial. Phlebology Non Baseline characteristics: Groups very unclear. anaesthesia.
2012; DOI: computer Miniophlebe Miniophlebe
226
comparable:
10.1258/phleb.2011.01114 randomisatio ctomies ctomies
7 n but clear Strip EVLA carried out carried out
allocation as required as required.
age 47.7(11.5) 47.7(12.9)
concealment.
No assessor %male 29.8% 31.7%
or other
Hach stages
blinding.
II 5.1% 7.1%
III 51.3% 51.4%
IV 43.7% 41.4%
No pre-op pain 62.4% 51.8%
Localised 11.3% 7.2%

lipodermatosis
Results:
Reference Study type No. of Patient characteristics Intervention Comparison Lengt Outcome Source
patients h of measure of
follow s fundin
-up g
Stripping EVLA p
Adverse Events
DVT 1/159 1/142
Lymphoedema 4/159 2/142
Neurological sensory deficits 2/159 3/142
Ecchymosis 100/159 72/142
Post op pain day 1 6/159 4/142
Post op pain 2-5 days 23/159 20/142
Post op pain >5 days 50/159 57/142
Saphenous nerve damage 1/159 5/142
SFJ reflux at 2 months 0/159 38/142 P<0.0001
227
Work disability (days) 9.2 9.3

VDS - asymptomatic 77/159 84/142
1
1 Table 71: Hinchcliffe 2006114
Hinchliffe RJ, Randomised 16 Inclusion: recurrent varicose Ligation and EVRF with 6 weeks, 1 None
Ubhi J, Beech within-subject patients. veins previously treated by inversion stripping VNUS year
A, Ellison J, design. The No sapheno-femoral ligation; all to just below the closure
Brathwaite researchers used reports CEAP 2 and above; persistent and knee. to just below system. The
BD. A a non-specified of loss to incompetent GSV suitable for the knee. probe was
prospective random method follow- treatment with EVRF; >18 yrs; retracted in
randomised to decide which up. 1cm
controlled side was treated Exclusion: pregnancy, twisted increments.
GSV, GSV <3mm, > 12mm; Common
trial of VNUS with what.
thrombotic scarring of GSV; no procedures:
Closure Allocation
GSV present. Multiple stab
versus concealment not
avulsions, general
surgery for applicable, as
Baseline Characteristics: 12 anaesthetic,
the the decision on
women, 4 men; median age 54 compression
228
treatment of the side would

(44-66 yrs); median CEAP: 3 (class bandages for 2
recurrent be made after
2, n=1, class 2, n=14, class 4, weeks.
long the recruitment.
n=1).
saphenous Patients
varicose reported to be
veins. Eur J blinded as to the
Vasc treatments used
Endovasc on each side,
Surg. 2006; assisted by the
31: 212-218. use of opaque
dressings over
the groin.
Assessor
photographing
patients’ legs for
assessment of
bruising was
blinded to
patient group.
Results: No variances given for continuous variables.

Surgery EVLA p
Post Ix pain (time point not given) [VAS]; 3.8 (0.6-6.3) 1.7 (0.2-4) 0.02
median (IQR)
Post Ix bruising (time point not given) 5.2 (2.6-7.0) 1.7 (0.4-4.4) 0.03
[VAS]; median (IQR)
% of bruising covering legs (time point 21.8 (15.7-28.5) 11.9 (8.9-18.3) 0.02
not given); median (IQR)
Adverse events
DVT 0/16 0/16
vessel perforation 0/16 0/16
PE 0/16 0/16
229
skin burns 0/16 0/16

lymphatic leak 0/16 0/16
post operative neuralgia 0/16 2/16
thigh discomfort 0/16 2/16
wound infection 1/16 0/16
numbness 3/16 0/16
leg oedema 1/16 0/16
non-fully stripped / non- occlusion 6 2/16 3/16

weeks
persistent incompetence in accessory 2/16 3/16
truncal veins 6 weeks
1
2
1 Table 72: Lurie2003152
Lurie F, RCT. Multi- 85 patients Symptomatic varicose veins and GSV Physicians EV radio- 72 hours, Disease VNUS
Creton D, site in 3 (86 limbs) incompetence, confirmed with duplex. followed their frequency 1 wk, 3 specific QoL medical
Eklof B, countries: 2 used. 45 standard obliteration. wks, and technologie
Kabnick LS, sites in USA, (46limbs) Inclusion: Reverse flow lasting .0.5 secs in practice using The Closure 4 months. s, inc. Clear
Kistner RL, 2 in France allocated standing; age 21-80 yrs; C2-4 either an olive- catheter and conflict of
classification; ambulatory; saphenous Occlusion
Pichot O, and 1 in to the tipped device system (VNUS interest.
vein < 1.2 cm in supine; segmental deep and reflex
Schuller- Austria. Each EVRF or a PIN med
reflux permissible. rates
Petrovic S, site had group and stripper. technologies)
Sessa C. performed at 40 to the Ligation in the was used
Exclusion: vein diameter >1.2 cm or <0.2
Prospective least 15 EVLs surgery femoral according to
cm. Duplication of saphenous trunk or
randomised as well as group. 3 triangle. established patient
incompetent accessory saphenous
study of “previous patients methods. reported
branch; small SV reflux; thigh varices; Common
endovenous experience” immediate symptoms
prev. DVT; ABI<0.9; axial DV reflux; procedures:
radiofrequen in the ly
230
twisted GSV segment to be treated. Adjunctrive

cy Stripping and withdrew
obliteration ligation after procedure on
Baseline characteristics: Adverse
(closure surgery discoverin varices and
perforator events
procedure) methods. g they
versus were in vessels limited
ligation and Randomisati the to below-knee.
stripping in a on unclear: surgery
“via EVRF surgery
selected group. A
patient internet”. further
Allocation Age 49 (4) 47 (4)
population surgery pt
(EVOLVeS concealment did not VCSS 4.8 (0.34) 4.39
study). J Vasc unclear. receive (0.38)
Surg 2003; treatment
Blinding
38: 207-14 due to Female 32 (74.4) 26 (72.2)
unclear. Bilat
non-
treatment of Working 25/44 25/36
attendanc
one patient
e. One
in the EVRF CEAP2 36/44 28/36
group, thus EVRF
artificially patient CEAP4 4/44 4/36
decreasing was
GA used 12/44 19/44
variance in withdrawn
that group. after Adjunctive 42/44 36/36
discovery phlebectomies
of previous done
surgery in
the same mean 8.6 (2.6) 9.8 (2.8)
vein. avulsions/extre
mity
One
further mean length of 37 (2) 40 (2)
EVRF treated segment
patient (cm)
was
231
withdrawn site 1 20 14
from
follow-up site 2 6 9
after he
site 3 7 7
was found
to have C6, site 4 9 3
a protocol
violation. site 5 2 3
Results: Comparisons of QoL scores were adjusted for the type of anaesthesia and number of adjunctive procedures.
EVRF Surgery
CIVIQ2 Disease specific QoL (0-100, 100 worst) global score (mean -3 (2.7) 13.3 (3.1)
(se)). Change from baseline to 72 hrs.
CIVIQ2 Disease specific QoL (0-100, 100 worst) global score (mean -9.2 (2.3) 3.7 (2.5)
(se)). Change from baseline to 1 wk
CIVIQ2 Disease specific QoL (0-100, 100 worst) pain dimension -1.77 (0.6) 2.9 (0.7)
(mean (se)). Change from baseline to 72 hrs
CIVIQ2 Disease specific QoL (0-100, 100 worst) pain dimension -2.4 (0.6) 1.2 (0.7)
(mean (se)). Change from baseline to 1 wk
CIVIQ2 Disease specific QoL (0-100, 100 worst) physical score 0.82 (0.69) 4.85 (0.79)
dimension (mean (se)). Change from baseline to 72 hrs
CIVIQ2 Disease specific QoL (0-100, 100 worst) physical score -0.97 (0.65) 2.02 (0.72)
dimension (mean (se)). Change from baseline to 1 wks
NB: The other two dimensions of the CIVIQ2 are not reported except the fact that they were NS. Data at later follow-ups not reported!
Occlusion and reflux rates
reflux at 72 hrs 5/43 0/36
reflux at 1 week unclear 0/36
complete occlusion of GSV at 72 hours 36/43 0/36
complete occlusion of GSV at 1 wk 41/43 0/36
232
complete occlusion of GSV at 3 wks 41/43 0/36

complete occlusion of GSV at 4 months 42/43 0/36
patient reported symptoms No reporting in any detail, except that EVRF showed a clear advantage for “pain”. The VCSS is
mentioned vaguely but no reports of any data except at baseline.
Adverse events at 72 hrs
none 19/44 6/36
infection 0/44 2/36
superficial venous thrombosis 0/44 1/36
tenderness 2/44 9/36
lymphocele 0/44 0/36
bleeding from stab wound 3/44 3/36
eccymosis 12/44 19/36
erythema 6/44 3/36
hematoma 7/44 14/36
paresthesia 5/44 2/36
hyper pigmentation 0/44 0/36
Adverse events at 1 week

none 15/44 5/36
infection 0/44 1/36
eccymosis 14/44 23/36
erythema 2/44 1/36
hematoma 6/44 18/36
233

Adverse events at 3 weeks

none 31/44 14/36
infection 0/44 1/36
eccymosis 1/44 7/36
erythema 1/44 3/36
hematoma 1/44 12/36
Adverse events at 4 months
none 36/43 26/34
ecchymosis 0/43 1/34
erythema 0/43 2/34
hematoma 0/43 3/34
Treatment failure 2/44 0/36
return to normal activity 1.15 (1.5) 3.89 (1.5)
0.02 (sds calculated from the p value
and MD)
1
2
234
1 Table 73: Lurie2005153
Lurie F, RCT. Follow up As Lurie See Lurie 2003. see Lurie 2003 see Lurie As Lurie Some outcomes not stated
Creton D, to Lurie 2003. 2003. 2003 2003, plus missing from
Eklof B, Please see In addition CEAP scores at 1 year and the Lurie 2003
Kabnick LS, table for Lurie This study baseline were reported as 2 years. paper are
Kistner RL, 2003. involved equivalent, with 82% and included in this,
Pichot O, follow-up 78% at C2 in EVLA and as well as new 1
Sessa C and at 2 further surgery respectively, 9% yr and 2 year
Schuller- time points: and 11% at C3 and 9% data.
Petrovic S. 1 year and and 11% at C4 (chi sq. 0.2,
Prospective 2 years. P=0.9).
randomised
At one QoL
study of
year, data
endovenous
were
radiofrequen
235
missing for
cy Reflux rates
21 limbs in
obliteration
the EVLA
(closure)
group and
versus
20 limbs Recurrence
ligation and
from the rates
vein stripping
surgery
(EVOLVeS):
group.
Two-year
follow-up. At 2 years, VCSS
Eur J Vasc data were
Surg 2005; missing for
29, 67-73 10 limbs in
the EVLA
group and
11 limbs
from the
surgery
group.
Results:
EVRF Surgery
reflux at 4 months 4/43
reflux at 2 years 2/36 3/29
Cumulative rates of recurrent varicose 14.3% 20.9% long rank

veins at combined 1 and 2 years test NS
follow-up
CIVIQ2 Disease specific global QoL at 1 Data only shown in figure (low resolution of figure and ambiguity about whether variance is sd or SE makes data
236
year and 2 years extraction impossible). However reported that the EVLA group had a significantly lower (better) QoL at 1 year and at 2
years.
CIVIQ2 Disease specific pain dimension Data only shown in figure (low resolution of figure and no variance indicators makes data extraction impossible).
of QoL at all time points However reported that the EVLA group had a significantly higher improvement in pain score (from baseline values) at
all time points from 72 hrs to 2 years.
VCSS Data only shown in figure (low resolution of figure and ambiguity about whether variance is sd or SE makes data
extraction impossible). However reported that the EVLA group had a significantly lower (better) VCSS at 72 hrs and 1
week (this was unreported in earlier report) but not significantly different at other time points
EVRF Surgery
% %
CEAP scores at 4 mths (analysed C0 34.1 C0 41.2

categorically with a chi square
analysis)
C1 38.6 C1 32.4
C2 18.2 C2 20.6
C3 0 C3 2.9
C4 9.1 C4 2.9
% %
CEAP scores at 1 yr (analysed C0 28 C0 15

analysis)
C1 56 C1 40
C2 8 C2 30
C3 0 C3 5
C4 8 C4 10
237
% %
CEAP scores at 2 yrs (analysed C0 33.3 C0 27.6

analysis)
C1 41.7 C1 31
C2 22.2 C2 31
C3 0 C3 3.4
C4 2.8 C4 6.9
Treatment failure See Lurie 2003

1
1 Table 74: Perala2005 204
Reference Study type No. of patients Patient Intervention Comparison Length of Outcome Source of
characteristics follow-up measures funding
Perala J, Rautio T, 3 year follow- see Rautio 2002. See Rautio 2002 Stripping surgery. Radiofrequency 3 years. Decrease in not stated
Biancari F, up of Rautio No further drop Groin dissected to endovenous VCSS
Ohtonen P, Wiik 2002. out from 50 days expose the SFJ. obliteration
H, Heikkinen T, to 3 years. Side branches of carried out VDS at 3 years
Juvonen T. the GSV at the SFJ with the VNUS
VSDS at 3 years
Radiofrequency were divided and Closure system
endovenous ligated. After local (see Lurie Satisfaction
obliteration phlebectomy, the studies). with cosmetic
versus stripping GSV was stripped result.
of the long from just below
saphenous vein in the knee to the Recurrence
the management groin with the
of primary venostrip with a Treatment
varicose veins: 3 9mm olive. failure
238
year outcome of a
randomised
study. Ann Vasc
Surg 2005; 19:
669-672.
Results:
EVRF Surgery p
Average decrease in VCSS from 4.3 (2.3) 4.0 (1.2) 0.7
baseline to 3 years [mean(sd)]
VDS at 3 years (median (range)) 0 in all except for 1 0 in all except for 1 1
VSDS at 3 years 0 in all except for 3 0 in all except for 1 0.6
Lack of satisfaction with cosmetic 1/15 2/13
result at 3 years
Would not recommend to a 0/15 0/13
friend
Reference Study type No. of patients Patient Intervention Comparison Length of Outcome Source of
characteristics follow-up measures funding
Recurrence of varicose veins as 5/15 2/13 0.4??
determined by surgeon
Recurrence of varicose veins as 4/15 2/13 0.065??
determined by patient
Reoperation for recurrent 1/15 1/13
varicose veins
Adverse events
symptom relating to saphenous 1/15 5/15
nerve injury 1/15 0/15
superficial thrombophlebitis
Treatment failure see Rautio 2002
Reflux 3/15 0/15
1
239
2
1 Table 75: Pronk2010213
Reference Study type No. of patients Patient characteristics Intervention Comparison Length of Outcome Source
follow- measures of
up funding
Pronk P, Gauw RCT. Non 130 legs in 122 All GP referrals with primary varicose High ligation of EVLA. 1 week, 6 Post op pain None
SA, Mooij MC, blinded. patients (EVLA veins. GSV and ligation Proximal weeks, 6
Gaastra MTW, Computer n=62; surgery of all tributaries 10cm of the months,
Lawson JA, van randomisation n=68). Patients Inclusion: >18 years; CEAP > 2; Reflux via groin incompetent 12
>0.5 secs on duplex; GSV diameter Symptoms
Goethem AR, used. No with bilateral incision, GSV treated months.
van Vlijmen-van reporting of VV were between 0.3 and 1.5cm. followed by PIN with an
Keulen CJ. allocation randomised stripping, with energy does
Exclusion: Previous surgery of the
Randomised concealment. only once. All access via of 100 J/min CEAP score
GSV; intrafascial GSV reflux length
controlled trial had treatment. incision below followed by
<15cm measured from SFJ
comparing the knee. a targeted
At 6 weeks, 2 downwards; pregnancy; immobility;
saphenofemoral energy dose
lost to follow- intolerance of lidocaine; active Common Patient
ligation and determined
up from superficial phlebitis; previous or deep procedures: satisfaction
stripping of the by the
240
surgery group, VT; deep venous insufficiency. Tumescent

great diameter of
saphenous vein none from the anaesthesia the GSV
with EVLA group. given to all. (0.3-0.4 – 50
endovenous The 2 lost to Surgery EVLA (n=62) Sclerotherapy of J/cm up to
laser ablation follow-up did (n=68) superficial >0.6 cm – 80
(980nm) using complete their varicose veins J/cm).
local tumescent post-op M:F 15:53 16:46 also given to all.
anaesthesia: questionnaires. Short stretch
one year There was Age 50(10.5) 49(11) bandages
results. Eur J further loss to applied to the
follow-up at 1 BMI 24.5(3.7) 25(3.3) whole leg for 1
Endovasc Surg
2010; 40: 649- year (7 further week.
Diam 0.64(0.14) 0.64(0.16)
656. lost in surgery
GSV
group and 6
further lost in tired legs 35/68 31/62
the EVLA
group) oedema 32/68 21/62
follow- measures of
up funding
itching 26/68 20/62
cosmetic 13/68 13/62
pain 13/68 9/62
restless 6/68 11/62

legs
calf 8/68 8/62

cramps
CEAP 2 26/68 29/62
CEAP3 36/68 29/62

241
CEAP4 5/68 4/62
CEAP5 1/68 0/62
Results:
Surgery EVLA P
Post-op pain during op 3.39(2.57) 2.21(2.40)
Post-op pain day1 4.00(2.34) 3.58(2.600
Post-op pain day2 3.12(2.38) 3.05(2.48)
Post-op pain day3 2.38(2.11) 2.76(2.53)
Post-op pain day7 1.78(1.94) 3.74(2.72)
Post-op pain day10 1.18(1.49) 2.65(2.21)

follow- measures of
up funding
Post-op pain day14 0.77(1.46) 1.66(2.04)
Tired legs 1 year 8/62 5/56 0.49
oedema 1 year 10/62 6/56 0.39
itching 1 year 6/62 3/56 0.50
cosmetic 1 year 8/62 4/56 0.31
pain 1 year 6/62 1/56 0.12
restless legs 1 year 4/62 7/56 0.43

242
calf cramps 1 year 2/62 5/56 0.25
CEAP 0 1 year 21/61 19/56 0.96
CEAP 1 1 year 22/61 20/56 0.97
CEAP 2 1 year 11/61 9/56 0.78
CEAP 3 1 year 6/61 7/56 0.65
CEAP 4 1 year 0/61 1/56
CEAP 5 1 year 1/61 0/56
QoL – cosmetic concerns (VAS) at 6 7 (4-10) 7.5 (3-10)

months [10 best]
Willing to do the same procedure again 53/67 47/61

follow- measures of
up funding
Would recommend to a friend or 59/67 51/61

relative
Adverse events
wound infection 0/67 0/61
DVT 0/67 0/61
post op bleeding 2/67 0/61
Thrombus at SFJ 0/67 3/61

243
persistent neurological injury (1 year) 1/67 0/61
Recurrence at 1 year (presence of reflux) 5/56 5/49
Recanalisation of GSV 3/49
return to normal activities 3.2 (4) 3.2 (4.3)
1
2
1 Table 76: Rasmussen2007219
Length of Outcome Source of

Reference Study type No. of patients Patient characteristics Intervention Comparison follow-up measures funding
Rasmussen RCT. 121 patients Inclusion: varicose veins, CEAP EVL done under High ligation 12 d, 1,3 Physician Public
LH, Bjoern L, Randomisatio (137 legs). C2-4 EpAsPr. Aged 18-80 yrs. duplex guidance and perforate and 6 outcomes - health
Lawaetz M, n method ITT reported as GSV incompetence defined by with a 980mm invagination months. VVSS insurance
Blemings A, unclear, but used, but unclear reflux >0.5 sec on duplex. diode laser, with stripping research
Lawaetz B, blocks of 10 about how the Previous high ligation was pulse mode, 1.5 performed QoL – disease foundation
Ekolof B. were used. loss to follow-up permitted. sec impulse, 1.5 through a specific of
Randomised Allocation were managed. Exclusion: Duplication of the sec pause and groin incision AVVSS Denmark.
trial concealment No evidence of saphenous trunk, incompetent 12W. GSV of 4-6 cm,
comparing achieved data imputation. anterior accessory GSV, previous accessed with flush
endovenous through percutaneously. division of the QoL – general
Loss to follow-up DVT, arterial insufficiency
laser sealed Catheter GSV and SF-36
(cumulative): and/or ankle-brachial index
ablation of envelopes. <0.9, axial deep venous advanced until 1- division of all
the great Two insufficiency and twisted GSV. 2 cm below tributaries Adverse
saphenous experienced saphenofemoral behind the events
vein with junction. second level
244
surgeons Baseline characteristics: (n

high ligation involved, but of the Treatment
represents number of legs). For
and stripping unclear Common division. If the failure
baseline values of outcomes,
in patients whether these procedures: vein broke
variance given is range.
with did both or Tumescent then
varicose Authors stated no group attempts
just one kind anaesthesia
veins: short differences. But note the were made to
of administered with
term results. numerical difference in C4 remove it
intervention. a syringe with US
J Vasc disease. from a more
Two centres guidance to the
Surgery also involved, GSV. Post surgery, distal position
2007; 46: but unclear compressive below the
308-15 how these bandaging knee.
were applied, and then
distributed replaced with a Common
across groups. class 1 procedures:
Bilateral compressive See
treatment stocking left in intervention
allowed, with situ for 2 weeks column.
the same (not entirely clear
treatment this was used for
given to both EVL Surg Surgery EVLA EVL patients,
legs (risk of A ery however). Both
artificial 12 2 0 prev 8/59 8/62 groups also had
reduction in d high lig multiple
variance). phlebectomies as
1 4 2 M:F 16:43 21:41 needed.
No blinding
mo Diclofenac given
achieved.
3 6 5 CEAP 2 51/59 50/62 as pain relief.
mo
6 15 18 CEAP4 3/59 9/62
mo GSV 7.6 (2.1) 7.9 (2.7)
diam
(mm)
245
reflux 2.5 (1.0) 2.6 (1.1)

time (s)
AVVSS 16.1 18.6 (3.6-
(4.4- 40.2)
34.3)
VCSS 2.4 (2- 2.8 (1-8)
12)
SF36 – 89.3 87 (25-
physical (25-100) 100)
function
SF36 – 89.3 87 (25-
role- (25-100) 100)
physical
SF36 – 77.1 76.6 (22-
bodily (22-100) 100)
pain
SF36 – 67.6 65.2 (32-
gen (28-80) 80)
health
SF36 – 73.1 69 (12.5-
vitality (12.5- 100)
100)
Results: For continuous variables, only mean and ranges given.
All outcomes measured at 3 months Stripping surgery Endovenous laser ablation
AVVSS 3 (score out of 100, with 100 worst symptoms) 8.2 (0-31.2) 6.9 (0-43.8)
VCSS 0.2 (0-2) 0.1 (0-2)
SF36 – physical function 92.2 (43.7-100) 93.9 (56.2-100)
SF36 – role-physical 92.2 (43.7-100) 93.9 (56.2-100)
SF36 – bodily pain 89.5 (31-100) 89.1 (32-100)
246
SF36 – gen health 66.7 (20-80) 67.7 (32-80)

SF36 – vitality 79 (37.5-100) 76.2 (18.7-100)
SF36 – social functioning 97.1 (12.5-100) 94.5 (37.5-100)
SF-36- role emotional 95.8 (58.3-100) 94.4 (33.3-100)
SF-36 – mental health 89.2 (60-100) 84.3 (25-100)
All outcomes measured at 6 months Stripping surgery Endovenous laser ablation
AVVSS (score out of 100, with 100 worst symptoms) 5.3 (0-33.1) 7.1 (0-38.7)
VCSS 0.2 (0-2) 0.4 (0-7)
SF36 – physical function 92.6 (50-100) 93.9 (43.7-100)
SF36 – role-physical 92.6 950-100) 93.9 (43.7-100)
SF36 – bodily pain 86.5 (20-100) 90.9 (51-100)
SF36 – general health 67 (33.6-80) 67.9 (40-80)
SF36 – vitality 82.9 (56.2-100) 77 (18.7-100)
SF36 – social functioning 98.8 (62.5-100) 98.2 (62.5-100)
SF-36- role emotional 95.7 (50-100) 95 (58.3-100)
SF-36 – mental health 90.2 (70-100) 86.2 (40-100)
Adverse events Stripping surgery Endovenous laser ablation
major complication – infection of groin (12days) 1/68 0/67
phlebitis (12days) 2/68 2/67
phlebitis (1month) 2/66 2/65
bruising (12days) 15/68 7/67
hematoma (12days) 5/68 3/67
hematoma (1month) 1/66 0/65
parasthsia (1 month) 0/66 1/65
paraesthesiae (6months) 1/50 0/54
NOT stripped /occluded 12 days 0/67 2/68
247
NOT stripped/occluded 1 month 0/65 2/66

NOT stripped/occluded 3 months 1/63 0/63
NOT stripped/occluded 6 months 3/53 1/50
time to resume normal activity (days) 7.7 (6.1) 6.9 (7)
Author's conclusions: The treatments were equally safe and efficient at eliminating GSV reflux.
1
2
Rasmussen LH, Bjoern L, RCT. Follow Follow up Follow up to Rasmussen Follow up to Follow up to 2 yrs Recurrence Public
Lawaetz M, Lawaetz B, up to to 2007 Rasmussen 2007 Rasmussen health
Blemings A, Eklof B. Rasmussen Rasmussen 2007 Insurance
Randomised clinical trial 2007 2007 Research
Clinical
comparing endovenous Foundation
severity score
laser ablation with of
stripping of the great Denmark
saphenous vein: clinical
outcome and recurrence Quality of life
after 2 years. Eur J Vasc
Surg 2010: in press. Doi:
10.1016/j.ejvs.2009.11.040
Results:
248
AVVSS, VCSS and domains of the SF36 were reported to not differ at 2 years, but no data given (except in very low resolution figures)
EVLA Surgery p
Recurrence (legs) at 2 years [note the denominators do 18/69 25/68 ns
not reflect the drop outs that occurred earlier in the
study, so ITT? But no mention of ITT or imputation].
Reflux into the AAGSV 6/69 3/69
Reflux in the groin 2/69 3/69
Reflux in thigh perforators 4/69 9/69
Reflux in lower leg perforators 3/69 6/69
Retreatment (mainly for cosmetic reasons) 9/69 6/69
2
3
2 See Table 63 for evidence table.
3 Table 79: Rass2011222
Rass K, Frings RCT. 400 Inclusion: GSV insufficiency with SF Endovenous Laser Flush ligation Post op, 3 Reflux None
N, Glowacki Randomisation randomised incompetence and reflux to knee therapy done with of SFJ and months, 1 reported
P, Hamsch C, method – 200 level; CVI and/or symptoms caused a 810mm diode invagination year and
Graber S, unclear. initially by GSV incompetence and/or severe laser, using stripping of 2 years.
Advers e
Vogt T, Tilgen Allocation allocated to clinical findings at risk of varicose Seldinger’s the GSV just
events
W. concealment each group. vein bleeding, thrombophlebitis and technique, and a below the
Comparable likely through DVT; age 18-65 years; performance 20W laser power. knee.
effectiveness use of an status, according to the American
of independent Society of Anaesthesiologists of class Common HVVSS (higher
15 did not procedures:
249
endovenous remote centre 1-11. means worse)

receive EVLT Tumescent Common
laser ablation for treatment
as they Exclusion: Previous groin surgery anaesthesia procedures:
and high allocation.
declined to except inguinal herniotomy; ant or administered. See
ligation with
Only one limb participate. post accessory saphenous vein Both groups also intervention CIVIQ-
stripping of
used per Of the 185 incompetence; small saphenous vein had multiple column. 2(higher
the great
patient. If who insufficiency requiring treatment; phlebectomies as means worse)
saphenous
bilaterally received thrombophilia; PAD; Malignant needed.
vein. Arch
affected the EVLT, 12 disease diagnosed in past 5 years; Analgosedation
Dermatol
worst limb were lost to pregnancy or lactation. using intravenous
2011; ecopy Patient
was used for follow-up midazolam
published assessed
the study. (11 refused Baseline characteristics: The allowed at the
online symptoms
or baseline characteristics of those for surgeon’s
unavailable whom outcome data is available are discretion given as
and 1 died). not shown. The baseline data below pain relief.
Each includes those lost to follow-up, and
treatment for whom no ITT was undertaken!
given in a
separate site, 39 did not EVLT Surgery
leading to risk receive
that site stripping as Age 47.9(10.9) 48(10.7)
effects, rather they
F 67% 70%
than declined to
treatment participate. BMI 26.2(4.1) 26.3(4.9)
effects, could Of the 161
explain study who CEAP 2 53/185 47/161
results. received
stripping, 18 CEAP3 95/185 76/161
were lost to
follow-up CEAP4 36/185 35/161
Blinding not
(18 refused
reported. CEAP5 1/185 2/161
or were
unavailable). CEAP6 0/185 1/161
250
HVVSS 16.1 (4.4- 18.6 (3.6-

No ITT done 34.3) 40.2)
– 173
GSV 8.7(2.8) 8.7(2.2)
evaluated in
diameter
EVLT group
at SFJ
and 143
(mm)
evaluated in
the stripping CIVIQ-2 28.6(19) 29.4(16)
group.
High risk of
attrition bias
due to
differential
loss to
follow-up
rates and no
ITT.
Results: For continuous variables, only mean and ranges given.
EVL Surgery
Reflux at 2 years 31/173 2/143

Adverse events
DVT 1/185 1/161
Phlebitis 20/185 4/161
Pain at 1 week 118/185 91/161
Pain (VAS) mean (sd) [higher worse] 1.6(0.8) 1.3(0.6)
Neural damage/injury 3 months
Hyper-pigmentation 3 months 17/185 22/161
251
57/185
19/161
HVSS 3 months 3.9(3) 3.8(3)
HVSS1 year 2(2) 2.1(3)
HVSS2 years 2.1(3)
1.9(3)
CIVIQ-2 [note only done on last 100 patients enrolled] – 3 months 12.8(14) [43] 18(16) [37]
CIVIQ-2 [note only done on last 100 patients enrolled] – 1 yr 10.5(14)[40] 11.1(14)[32]
CIVIQ-2 [note only done on last 100 patients enrolled] – 2 yrs 10.8(13)[41] 9.5(11)[33]
Pt reported pain from varicose veins (taken from CIVIQ) at 3 months 3(3) 4.6(4)
Author's conclusions: Both EVLT and HLS are comparably safe and effective procedures to treat GSV incompetence.
1
2
1 Table 80: Rautio2002224
Reference Study type No. of patients Patient characteristics Intervention Comparison Length Outcome Source
of measures of
follow- funding
up
Rautio T, RCT. 36 enrolled. 3 Patients scheduled for surgical Stripping surgery. Radiofrequency 7, 14, 28 Physician not
Ohinmaa A, Randomisation withdrew treatment of primary varicose veins. Groin dissected to endovenous and reported stated
Perala J, method because of an expose the SFJ. obliteration approx outcomes
Ohtonen P, unclear, but unsuitable Inclusion: A valsalver manoeuvre- Side branches of carried out 49-56 (VSDS, VCSS,
Heikkinen T, allocation schedule and induced reversal of blood flow the GSV at the SFJ with the VNUS days. VDS).
Wiik H, concealment so 33 were lasting > 2 seconds was considered were divided and Closure system Mean
Karjalianan likely through randomised. the threshold for inclusion. Patients ligated. After local (see Lurie 50 days.
P, Haukipuro sealed After suitable for day case surgery with phlebectomy, the studies). The
symptomatic, previously untreated QoL (RAND
K, Juvonen T. envelopes. randomisation, GSV was stripped catheter with
and complicated GSV tributary 36)
Endovenous 4 withdrew from just below sheathed
obliteration No evidence of from the varicosis and isolated unilateral SFJ the knee to the electrode was
versus blinding. stripping group and GSV trunk insufficiency were groin with the inserted
252
conventional due to eligible for the study. venostrip with a percutaneously Post-
All treatments
stripping disappointment 9mm olive. with US scan operative
performed by Exclusion: Coagulopathy, multiple,
operation in in being guidance into pain
the same tortuous and large diameter (>12 Common
the assigned to the GSV at the
single surgeon. mm) GSV trunks were excluded. procedures:
treatment of that group. A ankle level, and
Veins with a curve >90 degrees. General
primary further patient then passed up
anaesthetic given. Adverse
varicose withdrew from Baseline characteristics: Only age to the SFJ. The
Local phlebectomy events
veins: a the EVRF group was deemed different between entire length of
randomised because of and the GSV was
groups at baseline. Hence the small
controlled pregnancy. microsclerotherapy exsanguinated
numbers in each group did not lead
trial with Hence drop out performed as with Treatment
to chance differences of note at
comparison was surgery:4, necessary. Knee compression failure
baseline.
of the costs. EVRF 1. and groin anti- and elevation,
JVasc Surg mean (sd) unless stated. embolism stockings and the probe
2002; 35: Ultimately 28 used for first 7 was then
EVRF Surgery
958-965. participated, 15 days. slowly
in the EVRF age 33 (6.7) 38 (6.8)
withdrawn (3
group and 13 in F:M 14:1 12:1
of measures of
follow- funding
up
the surgery BMI 23.3(5.3) 24.0 (1.7) cm/min). To
group. A avoid damage
max GSV 6.4 (1.7) 6.1 (1.3)
further patient to the
diam.
“retired” saphenous
(mm)
[declined any nerve,
treatment?] Office/light 14/15 12/13 treatment was
but was not work kept above the
withdrawn heavy 1/15 0/13 medial tibial
from the study. work condyle.
It is not retired 0/15 1/13
reported from
which group VCSS 5 (4-9) 4 (4-6)
this patient (median
and range)
253
was.
VSDS 1 (1-1) 1 (1-1)
VDS 1 (1-2) 1 (1-1)
operation 75 (16.6) 57 (11)
time (mins)
Rand – 8 All were
dimensions similar
across
groups
Results:
EVRF Surgery p
VSDS (post operative). Median (range) 0 (0-0) 0 (0-1) 1
Decrease in VCSS [mean(sd)]. Unclear time 5.1 (1.5) 4.4 (1.1) 0.19
point.
VDS (post operative). Median (range) 0 (0-1) 0 (0-1) 1
of measures of
follow- funding
up
Adverse events (intraoperative)
groin hematoma 0/15 1/13
thermal skin injuries 3/15 0/13
Adverse events (post-operative)

saphenous nerve paraesthesiae 2/15 3/13
clinical thrombophlebitis 3/15 0/13
local heamatoma 1/15 4/13
thermal skin injury 1/15 0/13
total 7/15 7/13
Post-op Pain at rest (VAS) averaged over 0.7 (0.5) 1.7 (1.3) 0.017
254
first 14 days [mean(sd)]

Post-op Pain on standing (VAS) averaged 1.3 (0.7) 2.6 (1.9) 0.026
over first 14 days [mean(sd)]
Post-op Pain when walking (VAS) averaged 1.8 (0.8) 3.0 (1.8) 0.036
over first 14 days [mean(sd)]
RAND Physical functioning 1 week 30 (21-48) 50 (35-65) 0.07
[median(IQR)] for all
RAND Physical functioning 4weeks 0 (-5-4) 5 (0-10) 0.11
RAND role functioning physical 1 week 75 (38-100) 75 (25-100) 0.8
RAND role functioning physical 4weeks 0 (0-0) 0 (-25 – 0) 0.9
RAND bodily pain 1 week 23 (5-25) 38 (20-45) 0.05
RAND bodily pain 4weeks -23 (-28 -0) -10 (-33-0) 0.6
RAND general health perception 1 week 0 (0-8) 0 (-5 – 10) 0.7
RAND general health perception 4weeks -5 (-8 – 0) -5 (-5-10) 0.7
RAND energy 1 week 10 (-3 – 20) 0 (-10 – 15) 0.5
of measures of
follow- funding
up
RAND energy 4weeks -10 (-10-0) -10 (-25-10) 0.13
RAND social functioning 1 week 23 (0-31) 25 (13-50) 0.4
RAND social functioning 4weeks 0 (-13-0) 0 (0-0) 0.3
RAND role functioning emotional 1 week 0 (0-0) 0 (0-0) 0.9
RAND role functioning emotional 4weeks 0 (0-0) 0 (0-0) 0.5
RAND emotional well being 1 week -4 (-6 – 4) -4 (-8 -4) 0.7
RAND emotional well being 4weeks -4 (-8 – 4) -8 (-8-0) 0.4
Reflux 0/15 1/13 (reflux in an accessory
branch of the GSV
analgesic use (number of 600mg ibuprofen 0.4 (0.49) 1.3 (1.09)
tabs/day
255
1
2
1 Table 81: Stotter2006256
follow- funding
up
Stotter L, RCT. 60 patients Inclusion: Primary varicose veins; >0.5sec Ligation and EVRF with 24hrs, 1 Treatment None
Schaaf I, Randomisation (60 limbs).20 reflux on duplex. invagination VNUS week, 6 failure
Bockelbrink A. carried out by allocated to stripping to just closure weeks, 1
Comparative a statistical cryostripping Exclusion: requiring avulsion below the knee. system. Aim year.
outcomes of department, (NA). 40 phlebectomies in the thigh. to just below was to
Patient
radiofrequency but no other (20+20) the knee. increase
Baseline Characteristics: (all reported as satisfaction
endoluminal details given, allocated to temp. To 85
not different): Common
ablation, and no reports the two deg C and
invagination of allocation groups of procedures: the probe
Surgery EVLA (n=)
stripping, and concealment. relevance. 1 General was Physician
(n=)
cryostripping lost from Anaesthetic retracted at global
in the each group 3cm/min. assessments
256
M:F 5:15 6:14

treatment of at 1 year
great follow-up. age 54 men; 41 men;
saphenous 51 women 44
vein women
insufficiency.
2006; 21: 60- duration of 7.1 yrs 9.6 years
64. pathology
GSV diam. 7.1 (5-14) 6.8(4.5-

Distal to 12)
saphenofemoral
ostium
Results: No variances given for continuous variables.
Surgery EVLA
Physician global impression score (6 0.86 0.62

weeks?)[lower better]
follow- funding
up
Treatment failure (immediate in terms of 0/20 1/20

open segments)
Hematoma surface area at 1 week (cm2) 109 55
Numbers with heamatoma 24 hours 19/20 14/20
Numbers with heamatoma 1 week 18/20 11/20
Cumulative up to 6 weeks impairment score 7.9 2.8
Cumulative up to 6 weeks pain score 7.5 4.6
Adverse events up to 6 weeks

257
DVT 0/20 0/20
PE 0/20 0/20
Saphenous nerve injury 0/20 0/20
Treatment failure (Recanalisation or 2/19

neovascularisation)
Patient satisfaction with appearance of leg 1 7/19 17/19

year – very satisfied
11/19 2/19
Patient satisfaction with appearance of leg 1
year –satisfied 1/19 0/19
Patient satisfaction with appearance of leg 1

year – not satisfied
follow- funding
up
Patient satisfaction with treatment 1 year – 7/19 17/19

very satisfied
12/19 1/19
Patient satisfaction with treatment 1 year –
satisfied 0/19 1/19
Patient satisfaction with treatment 1 year –

not satisfied
1
2
258
1 Table 82: Subramonia2010B 258
follow- funding
up
Subramonia S, RCT. 93. 48 Inclusion: Patients with Tributaries of the GSV ligated. EVRF: GSV 1 CEAP None
Lees T. Randomisation randomised symptomatic varicose veins GSV ligated (high ligation). PIN accessed week,
Randomised using a web to EVRF and (CEAP 2-6); primary or stripper used. percutaneously, 5
clinical trial of based 45 to recurrent GSV reflux on and VNUS weeks.
Common procedures: Micheales
radiofrequency randomisation surgery. No duplex; patient fit for GA; Closure
Multiple phlebectomies. Both classification
ablation or method treatment: ambulatory. catheter
conventional stratified for EVRF: 1; groups had general anethetic. introducing,
high ligation age and sex. surgery 4 Exclusion: small saphenous Above knee graduated with tip just
and stripping No evidence of (not related or deep saphenous compression stockings worn below TCSS
for great allocation to trial or incompetence; twisted GSV for 2 weeks. Activity advice superficial
saphenous concealment. treatment above knee; GSV diam. <3 given. epigastric vein.
varicose veins. No blinding. allocation). or >12mm; GSV thrombus; With a target
259
pacemakers or internal VDS

British Journal No further temperature of
of Surgery loss to defibrillator; PAD [ABPI 85C the probe
2010; 97: 328- follow-up. <0.9]; pregnancy. was withdrawn
336. No ITT (i.e. at a rate of 1.5- AVVQ
those 2 cm/min for
No differences reported.
withdrawing the first 3cm
from EVLA Surge and then 1-3cm VEINES-
NB notes that
treatment (n=47) ry per min for the QoL/Sym
its companion
not (n=41) rest of the GSV.
paper, the HE
assessed,
paper, is
and no Age 47 45
excluded and
imputations (38- (37-
should go in
made). 58) 53)
exclusion list:
Subramonia S, M:F 13:34 14:27
Lees T.
Radiofrequenc CEAP2 37/47 33/41
follow- funding
up
y ablation vs.
conventional CEAP3 9/47 7/41
surgery for
CEAP 4- 1/47 1/41
varicose veins –
6
a comparison
of treatment TCSS 0 25/47 27/41
costs in a
randomised TCSS 1 12/47 7/41
trial. European
journal of TCSS 2 4/47 1/41
vascular and
TCSS 3 1/47 1/41
endovascular
Surgery 2010; TCSS >4
260
39: 104-111.
VDS 0 2/47 2/41
VDS 1 44/47 35/41
VDS 2 1/47 4/41
ASA 1 36/47 34/41
ASA II 11/47 7/41
Recurre 3/47 2/41

nt
Results:
EVLA Surgery P
Immediate treatment failure (? As immediately rectified in the case of 2/47 (occlusion failure, detected on 7/41 (complete
EVRF, not clear if we should refer to this as treatment failure) intra-op duplex, corrected after stripping not possible
follow- funding
up
immediate retreatment) for these)
1 week treatment failure (defined by duplex imagining of reflux in 0/47 5/41

GSV)
Adverse events
cutaneous sensory abnormalities 1 week 9/47 20/41 0.003
cutaneous sensory abnormalities 5 weeks 7/47 19/41 0.003
parasthesia 1 week 5/47 11/41 0.049
parasthesia 5 weeks 6/47 5/41 0.936

261
groin wound problems 1 week 0/47 7/41
non tender palpable GSV with overlying pigmentation 1 week 5/47 0/41
pain level (VAS) during first week post op (med[IQR]) 1.7 (0.5-4.3) 4 (2.35-6.05) 95% CI= -2.75, -0.79
numbers with pain requiring anaesthesia post op 30/47 40/41
satisfaction (VAS)(med[IQR]) 10 (8.4-10) 8.5 (7.5-10) 95% CI= 0.15, 1.44
Numbers completely satisfied (VAS score of 10) 27/47 11/41 0.004
numbers unwilling to recommend the procedure to others 1/47 9/41 0.005
TCCS and VDS Incomplete outcome reporting; “more than three quarters in each group had an improved
TCSS and VDS after surgery. Two patients, one in each group, had worsening of VDS by one
point after treatment”
improvement in AVVQ QoL score (mean; variance for each group not -9.12 -8.24 -3.64, 1.89; p=0.532
given, but CIs for the main difference given) 5 weeks [negative score
follow- funding
up
better]
V-Q/Sym Q analysis improvement in symptom score (mean; variance 12.62 9.94 -1.65, 7.01; p=0.220
for each group not given, but CIs for the main difference given) 5
weeks
V-Q/Sym Q analysis improvement in QoL score (mean; variance for 12.80 7.83 0.80, 9.14; p=0.02
each group not given, but CIs for the main difference given) 5 weeks
improvement in AVVQ QoL score (mean; variance for each group not -9.12 (6.405) -8.24 (6.405)
given, but CIs for the main difference given) 5 weeks
imputed by using the equation SE=
(upper – lower CI)/3.92, and then
converting SE OF THE MEAD DIFF to
262
within gp sd for each.
Actually /4.042 as used t dist for small

sample of 40.
1
Foam sclerotherapy vs. endothermal ablation
See Table 63 for evidence table

Table 83: Rasmussen2011221
G.5.3
263
3
4
1 Table 84: Lattimer2012 143
Reference Study Number of Patient characteristics Intervention Comparison Length of Outcome Source of
type patients follow-up measures funding
Lattimer CR et Random 110 Inclusion: Primary Outpatient FS – EVLA to GSV in 3 months AVVQ STD
al. Cost and ised randomised – symptomatic VV; SFJ max 12ml foam. 1% day surgery pharmaceut
effectiveness of controll 56 EVLA and 54 reflux on duplex; suitable STDS used. Injected theatre, using VCSS icals
laser with ed trial. FS. 6 did not for both techniques. into saphenous ELVes painless
Reflux
phlebectomies Number receive EVLA or trunk at knee level. diode laser;
compared with ed switched Exclusion: SPJ Tributaries treated 1470 nm; Post procedure
foam sealed groups and 4 incompetence, GSV as required on a tumescent pain
sclerotherapy in envelop did not receive >12mm; prev surgery or FS subsequent anaesthesia
superficial es used FS or switched of study leg; history of occasion using a 21 used. Access Return to normal
venous so groups. Per DVT; arterial occlusive gauge needle. point near knee. activities
insufficiency. probabl protocol disease (ABPI<0.8); active Incompetent
Early results of a e analysis used malignancy; pregnancy; saphenous
randomised allocati as only those known relevant allergies. tributaries
controlled trial. on completing treated
Baseline Characteristics
264
Eur J Vasc and conceal treatment (50 concurrently.

Endovasc Surg ment. and 50) EVLA Foam
2012; 43: 594- Blinding analysed at 3 sclero
600 not week follow-
carried up. Then 4 and Age 47.4 48.5
out. 5 (respectively) (21-74) (22-78)
Strictly lost to follow-
1 leg up at 3 month Fema 62% 54%
per follow-up. le
particip Overall, the
Bilat 56% 64%
ant- if loss was
disea
bilateral comparable
se
the across groups
worse so minimal risk CEAP
leg was of selection
studied. bias. 2 44% 20%
3 14% 16%
4 30% 48%
5/6 12% 16%
VCSS 6 (2-20) 7 (3-17)
AVVQ 20 (1- 25 (4-

53) 50)
VFI 4.7 5.9(1.1-

(0.9- 15.5)
17.8)
GSV 7 (4-12) 8 (5-12)

diam
BK 58% 74%
265
GSV
reflux
Results
p
EVLA Foam Sclerotherapy
Median (IQR) pain for 7 days after 33(18-54) 14(6-34) P=0.005 Man Whitney U test
treatment (VAS score with 100 worst
pain)
Median (IQR) time to return to 7.5(2-15) 3(1-10) P=0.011 Man Whitney U test
normal activities
Median days requiring analgesia 2(0-21) 0(0-14)
tablets
Reflux (Above knee) 3 weeks 1/50 8/50
Reflux (Above knee) 3 months 9/46 9/45
Reflux (Below knee) 3 weeks 7/50 24/50

Reflux (Below knee) 3 months 21/46 19/45
Need for further treatment 3/50 28/50 (but this may be because concurrent treatment
unavailable for FS group, in contrast to EVLA group)
Median (IQR) AVVQ at 3 months 5.8(2.5-12.2) 12.4(6-21.9)
Median (IQR) VCSS at 3 months 1(0-3) 2(1-4)
Median (IQR) VFI at 3 months 1.5(1.1-2.4) 1.9(1.3-2.7)
Change from baseline in AVVQ by 3 12 9 0.062
months
Change from baseline in VCSS by 3 3 3 0.721
weeks
Change from baseline in VCSS by 3 5 4 0.817
months
Change from baseline in VCSS VFI by 2.6 3.1 0.791
266
3 months
Adverse event: DVT 1/50 0/50
Adverse event: thrombosis 2/50 8/50
1
2
1 Table 85: Gonzalez-Zeh2008107
Reference Study type No of Patient Intervention Comparison Length of Outcome Source of

patients characteristics follow-up measures funding
Gonzales- Prospective 98. No Inclusion: Primary US guided foam Endovenous laser 1 week, 1 Reflux Not stated
Zeh R, cohort study patients incompetence of the sclerotherapy. ablation. GSV at month, 6
Armisen R, (effectively a non- dropped GSV and SFJ Policodanol was used the point of most months
Barahona S. randomised trial). out and insufficiency with a with a sclerosant to air distal reflux was and 1
VSCC
Endovenous Patients were all reflux time of 0.5 ratio of 1:4. Single punctured with a year.
laser and told each followed seconds measured injection using a 21 gauge needle
echo-guided treatment option up. over a distance of at venflon of 3% foam under US
foam was equivalent least 20cm in the applied with the guidance, and a
ablation in and were allowed upper leg. patient in supine. guide wire passed
great to choose their Injection at the point up the GSV,
saphenous own group [NB Exclusion: pregnancy; of most distal reflux in followed by a 5 Fr
vein reflux: this probably active GSV. Volume of introducer sheath
one year carries less of a thrombophlebitis, injection decided by to a point 1cm
follow-up bias risk than clotting disturbances; surgeon. Immediate 2 below the SFJ.
267
results. physician thrombophilia or minute compression 600 micron laser

Journal of allocation, as less coagulation disorders; applied afterward. filament passed
vascular risk, albeit in the history of DVT; history through the
surgery internet age, of of malignancies. Common procedures: sheath to a point
2008; 48: allocation based Full length class II 1 cm below the
Baseline compression stocking
940-6. on prognostic SFJ. Then it was
characteristics: applied 10 minutes
characteristics]. withdrawn at 1-2
Despite the lack of post procedure with
Only one limb per mm/sec in
randomisation the the patient lying
patient was continuous mode,
groups were well down. The stockings
included and with energy
matched. were to be continued
treated in this delivered by a
study. A single EVLA Sclero for 7 days and nights 980 nm diode
surgeon with n 45 53 continuously and for 7 laser at a power
experience of 800 additional days where of 15 W.
M:F 7:38 11:42
EVLA procedures usage in the day only
Age 51.1( 53.7( was required. Patients Common
and 2000 foam
11.9) 12) advised to walk for 30 procedures: See
sclerotherapy
CEAP 15/4 16/53 minutes immediately intervention
Reference Study type No of Patient Intervention Comparison Length of Outcome Source of
patients characteristics follow-up measures funding

procedures did 2 5 16/53 post procedure and to column.
both 3 16/4 10/53 walk daily for 30
interventions. 4 5 minutes. Simple non-
6/53
Patients were not 9/45 prescription analgesia
5 5/53
allowed to mix, to allowed for pain.
6 3/45
avoid
contamination of 2/45
patient supe 45/4 45/53
expectations. rficia 5
Clinical and l
ultrasound VCSS 3 (3- 3 (3-
follow-ups done (med 5) 5)
by a blinded ian[I
assessor. QR])
Results
268
EVLA Foam sclerotherapy p

Reflux at 7 days (not all reflux, includes open and flux) 0/53 4/45 not given
Reflux at 6 months (not strictly reflux, but referred to as partial 1/53 2/45 not given
recanalisation)
Reflux at 1 year (true reflux) 1/45 8/45 0.0360
Non occlusion at one year 3/45 12/45 0.04650
VCSS at 1 year (only includes those with no recanalisation at one 3(3-2) 2(3-2) No p for between group effects
year) [median (IQR)]
Adverse events
pain (VAS 1-10, 10 worst) 4.9 (1.5); n=45 4.0 (1.5); n=53 0.0082
phlebitis 10/45 22/53 0.0529
paraesthesia 2/45 1/53 0.5923
DVT 0/45 2/53 0.4982
1
1 G.5.4 Truncal and tributary treatment vs. truncal treatment alone
2 Table 86: Carradice 200946
Reference Study No. patients Patient characteristics Intervention Comparison Length of Outcome Source of
type follow-up measures funding
Carradice D, RCT. 50, 25 Inclusion: Patients with primary, Endovenous Endovenous 6 weeks AVVQ None
Mekako AI, “rando randomised to unilateral, symptomatic great laser therapy - laser (after 6 specified
Hatfield J, Chetter mised each group. Per- saphenous varicose veins; SFJ cannulation at therapy as weeks,
IC. Randomised to one protocol analysis incompetence and GSV reflux on the GSV. for sequential
SF36 & EQ-
clinical trial of of two used. In the duplex; perigenicular vein diameter 600nm laser intervention ambulatory
5D
concomitant or groups truncal > 4mm. fibre group, but phlebectomi
sequential using +tributary group introduced, with no es allowed
phlebectomy after sealed one was lost to Exclusion: Saphenopopliteal, small delivering 14 concomitant after this
endovenous laser envelop follow-up by 6 saphenous or deep venous W continuous procedures. time in the VCSS
therapy for es”. weeks, and all incompetence on duplex. 810 nm laser. Sequential comparison
varicose veins. Thus received Target energy ambulatory group).
269
British Journal of allocati intervention. In delivery was phlebectomi Further

Comparable for all baseline Return to
Surgery 2009; 96: on the trunk only 80-100 J/cm. es allowed follow-ups
variables. normal
369-375 conceal group, one was Concomitant after 6 were used at
activity and
ment withdrawn after truncal + truncal ambulatory weeks if 3 months
work
likely, not receiving tributary alone phlebectomy required. and 1 year.
but intervention, and of varicosities
method none others lost age 51.1(14.3 52.5(15.6) also carried
of to follow-up by 6 ) out. Stab Post
random weeks. Thus 24 incisions of 1- procedure
isation in each group M:F 8:17 4:21 2mm made pain
unclear. analysed (4% over varicose
loss in each – VCSS 4(2.25-5) 4(2-5) tributaries,
unlikely to cause and veins Obliteration
SF-36 85(70- 93(80-100)
bias) at 6 weeks. avulsed.
physical 99)
At 3 months,
further losses to This is not
SF-36 74(51- 79(55-100)
follow-up led to clear, but looks Need for
bodily 84)
23 in the truncal likely that further
pain
+ tributary group BOTH groups procedures
and 22 in the AVVQ 13.29(11. 13.75(11.67 had an elastic
trunk only group, 09- -15.82) bandage
and at 1 year the 15.50) applied to the
analysed figures leg for 1 week,
EQ-5D 0.796(0.7 0.796(0.778
were 20 and 21 and replaced
69-1) -1)
respectively. by a class II
(20-30 mmHg)
full length
graduated
support
stocking for a
further 5
weeks.
Results:
270
Trucal + tributary Truncal only p

AVVQ 6 weeks (lower better) [median(IQR)] 7.9 (4.1 – 10.7)[24] 13.5 (10.9 – 18.1)[24] <0.001
AVVQ 3 months 2.0 (0.4-7.7) [23] 9.6(2.2 – 13.8) [22] 0.015
SF-36 no results given in text (only in low resolution graph)
EQ-5D
Reflux at 1 week 0/24 0/24
SFJ Reflux at 1 year 1/20 2/21
GSV reflux at 1 year 2/20 1/21
VCCS at 1-6 weeks (lower better) no data no date
VCSS at 3 months 0(0-1) [23] 2(0-2) [22] <0.001
VCSS at 1 year 0(0-1) [20] 1(0-1) [21] 0.433
Adverse events
phlebitis 0/24 1/24
pigmentation 2/24 0/24
thigh “neuralgia” 1/24 0/24
post op pain no data but recorded no difference between groups at days 1,3 and 7
return to work (days) 10 (4-21) 3(1-14) 0.054
return to normal activity (days) 8(1-14) 2(1-5) 0.166
need for subsequent ambulatory phlebectomy at 6 weeks 1/25 16/24
Patient satisfaction (would recommend to a friend or 20/20 19/21
would have it again)
1
2
271
G.6 Chapter 10 – compression after interventional treatment
2 Table 87: Hamel-Desnos 2010111
Hamel-Desnos RCT. Method of 60 (31 in Inclusion: Patients presenting Foam Foam 1 month reflux at 1 Some
CM, Guias BJ, randomisation combination, for treatment of symptomatic sclerotherapy sclerother month after funding (for
Desnos PR, unclear. It is 29 in varicose veins; aged >18; using one apy using treatment. stats) by
Mesgard A. Foam stated that sclerotherapy incompetence of the GSV or volume of one compressio
sclerotherapy of randomisation only). No SSV; trunk diameter >8mm for aetoxisclerol volume of QoL n stocking
the saphenous was done 5-10 drop-outs GSV and 6mm for SSV; venous and 4 volumes aetoxiscler company, as
Patient
veins: randomised minutes after reported. reflux lasting at least 1 sec; C2- of sterile air. ol and 4 well as free
assessed
controlled trial sclerotherapy 6. Up to 3 volumes of stockings.
symptoms
with or without using a sessions were sterile air.
compression. Eur J randomisation Exclusion: Any factors limiting permitted. Up to 3 Adverse
Vasc Endovasc list provided by the ability to participate in an sessions
272
events
Surg 2010; 39: the statistician. informed manner; isolated SFJ 5-10 minutes were
500-507 It is therefore incompetence; post-surgical after the first permitted.
likely that there recurrence of varices without sclerotherapy
was no trunk recurrence; chronic liver session, class No
allocation or renal disease; 2 French compressi
concealment. pregnancy/lactation; standard 15- on given.
There were two malignancy; history of DVT; 20 mmHg
study centres cardio-vascular/respiratory stockings
and two problems; Coagulopathy; (thigh length
regions of alcohol intolerance; allergies; for GSV and
treatment patent foramen ovale; previous knee length
(great or small migraine or CNS disturbance for SSV) were
saphenous after sclerosing therapy; lycra applied, to be
vein) and allergy; inability to apply worn during
randomisation compression. the day for 3
was stratified weeks
Only difference was for following
for these. No
age(p=0.018); overall mean
mention of CEAP class was 2.6 (range 2-6) treatment.
blinding.
Sclero + sclero only

compre
ssion
age 61(11) 53(14)
%men 13 3
GSV 19/31 17/29

affected
Results:
Sclerotherapy plus compression Sclerotherapy only p
Reflux at 28 days 0/31 0/29
273
CIVIQ 2 QoL global score – change from baseline -5.5 (10) [22] -9 (9.9) [21]
day 14 (-ve change = improvement)
CIVIQ 2 QoL global score – change from baseline -9.4 (10) [23] -11 (14) [24]
day 28 (-ve change = improvement)
rate of improvement at day 28 reportedly no difference between groups
heavy legs (20/30) 67% (16/29) 55%
pain (21/30) 70% (17/29) 59%
oedema (15/30) 50% (15/29) 52%
paraesthesia (17/30) 57% (13/29) 45%
cramp (11/30) 37% (16/29) 55%
NB: the denominator of 30 for the combination group and 29 for the sclera only group led to the best agreement with the
percentages given in the paper (no denominators given in the paper).
Patient satisfaction with sclerotherapy
“very effective” day 14 15/30 20/29
“very effective” day 28 22/30 19/29
Patient satisfaction with COMPRESSION 7/30
“very effective” day 14
Adverse events
major neurological events <24 hrs 0/31 0/29
visual disturbance (scotoma) resolving within 15 0/31 1/29
mins
moderate pain day 28 1/30 3/29
pigmentation 2/30 1/29
compliance with compression
number wearing every day 12/30
mean number of days use (max 21days) 11
274
1
2
1 Table 88: Houtermans-Auckel 2009118
Houtermans- RCT. 104 randomised – Inclusion: Primary varicose veins Crossectomy and Crossectomy 4 weeks post –op None
Auckel JP, van Random 52 allocated to due to GSV reflux; complete short GSV and short GSV post-op pain (VAS)
Rossum E, Teijink ised each group. 2 incompetence of the GSV on inversion inversion
JAW, Dahlmans using patients in the duplex US; C2-C3; stripping, done as stripping, Post
AAHR, Eussen EFB, comput comparison group day surgery, 90% done as day operative
Nicolai SPA, er and 6 patients in Excluson: Patients unable to of which was surgery, 90% adverse
Welton RJTJ. To generat the intervention wear compression stockings; under spinal of which was events
waer or not to ed group dropped out patient who had already used anaesthetic. under spinal
compression stockings; patients Return to
wear compression random 3 days post- Standard elastic anaesthetic.
with ulcers. full activity
stockings after isation operatively (prior bandaging with a Standard
varicose vein list. to starting the 4 rolled gauze over elastic
stripping: a Closed weeks the proximal part bandaging
randomised envelop compression). Described as comparable. of the GSV with a rolled
controlled trial. es used, These drop-outs applied for 3 gauze over the
275
Eur J Endovasc with were thus not due Ix Comparis days. proximal part
Surg 2009; 38: pre- to lack of efficacy on of the GSV
387-391. random or adverse events applied for 3
isation of compression as Men% 27 37 days.
Then fitted with
allocati an adjunct, and
age 50 49 class 2 medical
on this unlikely to
compression
conceal cause bias. All
R leg % 69 73 stockings No further
ment. unavailable for
(measured fit), at compression
No follow-up. Muller 52 48 23-32 mmHg for 4 given.
blinding Available case phlebecto weeks, day and
after analysis done, my done night for the first
random with 46 analysed as well 2 weeks and then
isation. in the intervention
day only for the
group and 50 in
final 2 weeks.
the comparison
group.
Results:
Surgery plus Surgery only
compression
Adverse events
post op pain (VAS) at 3 days 2.5(2.8)[46] 1.8(2.2)[50]
post op pain (VAS) at 2 weeks 2.2(2.3)[46] 2.2(2.4)[50]
post op pain (VAS) at 4 weeks 0.8(1.5)[46] 0.5(0.8)[50]
Numbness 3 days 4/46 3/50
Bleeding 3 days 0/46 0/50
Infection 3 days 2/46 1/50
Seroma 3 days 2/46 1/50
276
Return to work (measured at 4 weeks) 15(8.4)[46] 11(7.5)[50]

1
G.7 Chapter 11 - Pregnancy
2 Table 89: Mota-Capitao 1995175

No. of Length of Source of
Reference Study type patients Patient characteristics Risk factors studied Outcome measures follow-up funding
Mota-Capitao L, Cross- 474 patients Not all patients had CVI. Many “risk factors” in this A linear relationship NA Not stated
Menezes JD, sectional for presenting 4% were class 0 CVI study were measured between the risk
Gouveia- many to 18 (asymptomatic), 42% class cross-sectionally, but factors and the ordinal
Oliveira A. variables, different 1 (mild), 33% class 2 potentially prognostic outcome variable (class
Clinical but GPs with CVI (moderate) and 21class 3 variables are age, sex, of CVI) was taken as
predictors of effectively a symptoms. (severe). 70% had a pregnancy, parity, evidence of an
the severity of case-study history of varices. 3% had hormones, family history, association of the risk
chronic venous for the a history of DVT. 90% had medication and past factor with progression
insufficiency of potentially had symptoms for > 1 medical history. of CVI. However, only
the lower limbs: prognostic year. HHD used to retrospective risk
a multivariable variables of “confirm” diagnosis. factors could be said to
analysis. family have a causative effect.
277
Phlebology history and

1995; 10: 155- past medical
159. history.
Results:
After multivariable analysis of factors having a linear relationship with CVI class, the potentially prognostic variables that remained in the model were as follows:
Factor co-efficient p
age 0.036 <0.001
CVI in both parents 0.568 0.026
History of thrombophlebitis 0.775 0.019
History of post-thrombotic syndrome 1.627 0.028
History of lymphoedema 1.712 0.026
3
4
1 Table 90: Fischer 200698
3 Table 91: Zubilewicz 2009290
5 Table 92: Thaler 2001260

Thaler et al. Randomise 45 randomised. 3 Inclusion: Pregnant women with Two No stocking Up to 6-8 Emergence Ganzioni,
Compression d controlled drop outs from uncomplicated pregnancies <12 weeks treatment control weeks post- of any a stocking
stockings study. No treatment in gestation; absence of GSV reflux at SFJ. groups: group group partum varicose manufactu
prophylaxis blinding for group 1 of the 1 wore class I veins rer,
of emergent patients or intervention Exclusion (post entry): intolerance of compression (including provided
varicose HCP but group (see compression; miscarriage tights on the reticular stockings
278
veins in blinding of Intervention left leg and veins) and

pregnancy: a assessors. column) due to class II on the Duplex “logistic
prospective No mention miscarriage, Baseline characteristics: right leg; support”.
evidence
randomised of relocation abroad Contr Gp 1 Gp group 2 wore of GSV
controlled randomisati and failure to re- ols 2 class II reflux (>2
study. Swiss on method attend. No drop Maternal 28.8( 29(5) 33( compression secs).
Med Weekly nor of outs in the other age 5) 4) tights on the
2001; 131: allocation groups. There left leg and
parity 2(1.4) 1.7(0.9) 2.2
659-662. concealmen were 9 losses of class I on the
(0.8
t. Stratified final follow-up right leg; This
)
randomisati data (controls: 3, mirror division
on for group 1: 2; group Numbers 9/15 7/12 8/1 was to
venous 2: 4) but all were with 5 exclude a
status at included in the varicose laterality bias
entry (slight analysis using veins at in varicose
varicose earlier follow-up entry vein
changes measures. emergence.
present/abs Attrition bias However for
ent). minimal as there the purposes
was only a 10% of the review
differential in the results for
drop out between group 1 and 2
combined group have been
1,2 and the merged.
controls.
Results:
controls Group 1 Group 2 p
Patients with emergent varicose veins at 1 week 7/14 5/12 8/14 0.94
post-partum 13/26
Patients with emergent third trimester GSV reflux 4/15 1/27 0.047
at the SFJ during 3rd trimester
Leg symptoms at one week postpartum – better 0/14 3/12 4/14 0.03
279
than baseline 7/26

Evidence tables economic studies
1 Appendix H: Evidence tables economic studies

2 H.1 Chapter 7 – assessment for treatment
3 Table 93: Blomgren 2006A
L. Blomgren, N. Zethraeus, G. Johansson, B. Jonsson, and D. Bergqvist. Cost consequences of preoperative duplex examination before varicose vein surgery: a
randomized clinical trial. Phlebology 21 (2): 90-95, 2006.
Study details Population & interventions Costs Health outcomes Cost effectiveness
Economic analysis: CC Population: Patients aged Mean cost per patient: Quality of Life: ICER:
Study design: RCT – 20-75 admitted to hospital Intervention 1: SEK 13,051 No significant difference (no NR
with varicose veins. Excluding 25
Within trial analysis (£900) further data reported). Analysis of uncertainty: Uncertainty was not
Approach to analysis: those with pure cosmetic Intervention 2: SEK 11,193 explored.
Comparison of costs complaints, previous venous (£772)
surgery or sclerotherapy,
280
arising in the first 2 Incremental (2-1): SEK 1,858

years of varicose vein history of suspected or
(£128)
treatment manifest deep venous
thrombosis, active or healed Currency & cost year:
Perspective: Care- 2004 Swedish krona
leg ulcer, peripheral arterial
giver in Sweden (direct (presented here as 2004 UK
disease, previous significant
costs only) a
pounds )
trauma to the leg, general
Time horizon: 2 years illness and drug or alcohol
Discounting: Costs = abuse. Cost components
3%; Mean age: Duplex = 48 years, incorporated:
No duplex = 45 years. Costs for staff, physicians,
Gender: Duplex = 37% male, colour flow duplex imagers
No duplex = 33% male and overhead costs,
Intervention 1: operating room costs
Duplex for pre-operative (including salaries for
examination on top of anaesthetic and theatre staff,
participating surgeons’ drugs, materials for cleaning
standard procedure for and draping, gowns and
clinical examination (varied gloves), extra operative costs
by surgeon, sometimes (ie for preoperative

included hand-held Doppler mapping), and admission
24
testing). costs if the patient was
Intervention 2: required to stay overnight.
Participating surgeons’
standard procedure for
clinical examination (varied
by surgeon, sometimes
included hand-held Doppler
testing) only.
Data sources
Cost sources: All costs were taken from the hospital accounting system (Capio St Göran’s Hospital, Stockholm, Sweden).
Comments
Source of funding: NR. Limitations: The time horizon was restricted to two years and thus may not fully capture cost differences between the different assessment
strategies; costs of re-treatment post 2 years which are likely to favour use of duplex will not have been captured. Uncertainty is not formally explored, but the authors
note that with a longer follow-up the use of duplex could be cost-saving. QALYs are not considered, therefore no ICER can be presented. Finally, unit costs and resource
281
use estimates are obtained from the trial only, rather than via a systematic procedure.
b c
Overall applicability : Partially applicable Overall quality : Potentially serious limitations
1 Abbreviations: CC = cost comparison; ICER = incremental cost-effectiveness ratio; NR = not reported; QALYs = quality-adjusted life years; SEK = Swedish Krona
195
2 (a) Converted using 2004 purchasing power parities
3 (b) Directly applicable / Partially applicable / Not applicable
4 (c) Minor limitations /Potentially serious limitations / Very serious limitations
5
H.2 Chapter 8 – conservative management
2 Table 94: GOHEL2010106 See Table 97: GOHEL2010
3 Table 95: MICHAELS2006170

J. A. Michaels, W. B. Campbell, J. E. Brazier, J. B. Macintyre, S. J. Palfreyman, J. Ratcliffe, and K. Rigby. Randomised clinical trial, observational study and assessment
of cost-effectiveness of the treatment of varicose veins (REACTIV trial). Health Technol.Assess. 10 (13):1-196, 2006.
Economic analysis: Population: Mean cost per patient: Primary outcome measure:
CUA Patients with primary QALYs (mean per patient)
varicose veins. Subgroups: Moderate varicose veins Moderate varicose veins Moderate varicose veins (Group 2)
Study design: ‘moderate’ varicose veins Intervention 1: £473 (Group 2)Intervention 1: Intervention 2 versus Intervention 1:
Decision-analytic with reflux; and ‘severe’ 6.589 QALYs
Intervention 2: £920 ICER: £2,089 per QALY gained (d/a)
Markov models were varicose veins. Intervention 2: 6.803 QALYs
Incremental (2-1): £447
built for three Incremental (2-1): 0.214 Severe varicose veins (Group 3)
different patient Cohort settings:
282
QALYs
groups. Severe varicose veins Intervention 2 versus Intervention 1
Start age = 46 years
Intervention 1: £0 ICER: £1,938 per QALY gained (d/a)†
Female = 90% Severe varicose veins (Group
Approach to analysis: Intervention 2: £880
3)Intervention 1: 6.341
Cost effectiveness Incremental (2-1): £880 QALYs Analysis of uncertainty:
Intervention 1:
modelling was over a Intervention 2: 6.795 QALYs Univariate sensitivity analysis performed on:
Conservative treatment
period of 10 years (120 Currency & cost year: costs of surgery, costs of major complications
Incremental (2-1): 0.454
cycles). The analysis 2003 UK pounds after surgery, probability of residual veins
Intervention 2: QALYs
was not based solely after surgery, probability of minor
on data from the 2- Standard surgery complications after surgery and difference in
(saphenofemoral ligation, Cost components the progression rate of reflux versus no
year randomized
stripping and multiple incorporated: reflux.
controlled trial
because of small phlebectomies) Initial costs of treatment
sample size. A (surgery, sclerotherapy),
Generally, the cost-effectiveness results are
separate within-trial costs of retreatment, hospital
Liquid sclerotherapy was also fairly robust to the univariate and
economic analysis was admission/visits, visits to the
included as a comparator; multivariate sensitivity analyses. All ICERs fall
also carried out; GP, practice nurse and other
results are not presented below £20,000 per QALY.
results are as in healthcare professionals
here.
J. A. Michaels, W. B. Campbell, J. E. Brazier, J. B. Macintyre, S. J. Palfreyman, J. Ratcliffe, and K. Rigby. Randomised clinical trial, observational study and assessment
of cost-effectiveness of the treatment of varicose veins (REACTIV trial). Health Technol.Assess. 10 (13):1-196, 2006.
Radcliffe et al (2006) (e.g., visits to the A&E and
223
anticoagulation units).
Perspective: Also included are costs of

UK NHS developing major or minor
Time horizon: 10 yrs surgical complications, and
costs of co-morbidity.
Treatment effect
duration: 10 yrs
Discounting: Costs =
3.5%; Outcomes =
3.5%
Data sources
Health outcomes: Some outcomes (for example, risk of complications following surgery or sclerotherapy, and rate of progression/recurrence of varicose veins) were
taken from the randomized controlled trial contained in the report. Other outcomes (for example, probability of progression with reflux and progression without reflux)
283
228
were informed by systematic reviews including Rigby et al. 2004 .
34
Quality-of-life weights: Derived from SF-6D and EQ-5D scores. SF-6D scores were calculated from SF-36 data using an algorithm developed by Brazier et al. 2002 .
Cost sources: Unit costs for all resources used by patients in the randomized controlled trial were obtained from the data sources in the UK including the NHS
Reference costs, the Personal Social Services Research Unit and the British National Formulary (BNF). Data on resources use collected from the randomized controlled
trial.
Comments
Source of funding: NHS R&D Health Technology Assessment (HTA) programme; Limitations: The retreatment options and rates of retreatment modelled are based on
expert opinion, although no detail is given on the expert(s) or how this information was elicited. The clinical pathway is based on strict assumptions of who can receive
which treatment, and may not fully reflect what happens in current practice. Utility data is based on an average of SF-36 and EQ-5D data; no reason is given.
Overall applicability*: Directly applicable Overall quality**: Minor limitations
1 Abbreviations: CUA = cost-utility analysis; d/a deterministic analysis ICER = incremental cost-effectiveness ratio; NR = not reported.
2 †The within trial analysis was conducted for this group – results are as presented in Ratcliffe et al 2006 (Table 96)
3 ^ Surgery shows extended dominance over sclerotherapy in that a blend between conservative treatment and surgery offers better value for money than sclerotherapy;
4 * Directly applicable / Partially applicable / Not applicable; ** Minor limitations /Potentially serious Limitations / Very serious limitations
5
1 Table 96: RATCLIFFE2006223
J. Ratcliffe, J. E. Brazier, W. B. Campbell, S. Palfreyman, J. B. Macintyre, and J. A. Michaels. Cost-effectiveness analysis of surgery versus conservative treatment for
uncomplicated varicose veins in a randomized clinical trial. Br.J.Surg. 93 (2):182-186, 2006.
† † †
Economic analysis: Population: Mean per patient: Primary outcome measure: Intervention 2 versus Intervention 1
CUA Patients with uncomplicated Intervention 1: £345 QALYs per patient (using SF-6D (using SF-6D scores):
varicose veins and evidence Intervention 2: £733 scores, n=94) ICER: £4,682 per QALY gained (pa)
Study design: of saphenofemoral or Incremental (2-1): £389 Intervention 1: 1.420 QALYs 95% CI for ICER: £2,039 to £20,830 per
A randomized saphenopopliteal reflux. Intervention 2: 1.503 QALYs QALY gained
(95% CI: 282 to 506; p < 0.05)
controlled trial Patients with recurrent
Incremental (2-1): 0.083 QALYs
conducted at two varicose veins were
Currency & cost year: (95% CI: 0.005 to 0.162; p < Probability cost-effective:
vascular units within excluded.
2002-2003 UK pounds 0.05) With a threshold of £20,000 per QALY and
the NHS. QALY estimates based on SF-6D scores,
Cohort settings: the probability that surgery is cost-
Cost components Other outcome measures
Approach to analysis: Start age = NR effective was 70%. At a £30,000 per QALY
incorporated: (mean):
Economic analysis Male/ Female = NR threshold, the probability increases to
Hospital inpatient QALYs per patients (using EQ-
284
based on the 2-year 76%.

admissions, surgical 5D values, n=91)
data from the Intervention 1:
treatments, outpatient visits, Incremental (2-1): 0.133 QALYs
randomized controlled Conservative treatment Analysis of uncertainty:
trial other NHS visits (to the A&E,
(compression therapy plus anticoagulation clinics, GP or Uncertainty around cost-effectiveness was
lifestyle advice) practice nurse), retreatment assessed using bootstrap methods. The
Perspective: UK NHS N=124 costs, compression hosiery percentiles from the bootstrap
Time horizon: 2 years and treatment of replications were used to derive the cost-
Treatment effect complications. effectiveness acceptability curve.
Intervention 2:
duration: 2 yrs Stripping surgery
Discounting: Costs = Sensitivity analysis showed that the
N=122
3.5%; Outcomes = economic results are fairly robust. Using
3.5% EQ-5D values (instead of SF-6D scores)
gives an ICER of £3,299 per QALY. Using
NHS Reference Costs for surgical
treatment (instead of local unit costs)
gives an ICER of £5,708 per QALY.
Data sources
J. Ratcliffe, J. E. Brazier, W. B. Campbell, S. Palfreyman, J. B. Macintyre, and J. A. Michaels. Cost-effectiveness analysis of surgery versus conservative treatment for
uncomplicated varicose veins in a randomized clinical trial. Br.J.Surg. 93 (2):182-186, 2006.

169
Health outcomes: This was taken from the results of the randomized controlled trial reported by Michaels et al. 2006 .
Quality-of-life weights: SF-36 questionnaire scores at 1, 6, 12 and 24 months of follow-up were translated into preference-based SF-6D scores using the algorithm
34
developed by Brazier et al. 2002 . EQ-5D scores were also considered.
Cost sources: NHS Reference Costs and Personal Social Services Research Unit. Where national data was not available, local unit costs were obtained from the finance
departments of two hospitals.
Comments
Source of funding: NHS R&D Health Technology Assessment (HTA) programme; Limitations: No decision analytic model was conducted to capture long-term costs and
health outcomes. The short 2-year time horizon may underestimate the cost-effectiveness of surgical treatment as the clinical benefits of surgery including
improvements in health-related quality of life would be expected to endure beyond 24 months. Including long-term costs and health outcomes may still give lower
ICERs.
Overall applicability*: Directly applicable Overall quality**: Minor limitations
1 Abbreviations: CI = confidence interval; CUA = cost-utility analysis; d/a deterministic analysis; ICER = incremental cost-effectiveness ratio; NR = not reported; pa = probabilistic analysis *
2 Directly applicable / Partially applicable / Not applicable; ** Minor limitations /Potentially serious Limitations / Very serious limitations
170
3 †These results are also presented in Michaels 2006
4
285
H.3 Chapter 9 – interventional treatment
2 Table 97: GOHEL2010

M. S. Gohel, D. M. Epstein, and A. H. Davies. Cost-effectiveness of traditional and endovenous treatments for varicose veins. Br.J.Surg. 97 (12):1815-1823, 2010.
Economic analysis: Population: Mean cost per patient: Primary outcome measure: ICERs
CUA Patients with unilateral Intervention 1: £0 QALYs (mean per patient) Intervention 2 versus Intervention 1:
symptomatic primary Intervention 2: £429 Intervention 1: 3.522 QALYs £1,366 per QALY gained (d/a)
Study design: saphenous varicose veins Intervention 3: £1,031 Intervention 2: 3.836 QALYs Intervention 3 versus Intervention 2:
Decision-analytic Intervention 4: £1,110 Intervention 3: 3.940 QALYs £5,799 per QALY gained (d/a)
Markov model Cohort settings: Intervention 5: £1,242 Intervention 4: 3.944 QALYs Intervention 4 versus Intervention 3:
Start age = NR Intervention 6: £1,915 Intervention 5: 3.951 QALYs £17,350 per QALY gained (d/a)
Approach to analysis: Male/Female = NR Intervention 7: £1,964 Intervention 6: 3.954 QALYs Intervention 5 versus Intervention 4:
The model considers in
Intervention 8: £2,000 Intervention 7: 3.951 QALYs £19,012 per QALY gained (d/a)
the first 3 months the Intervention 1:
following outcomes: Intervention 8: 3.954 QALYs Intervention 7 versus Intervention 5:
286
Conservative care Currency & cost year: £100,451 per QALY gained (d/a)
(1) initial intervention
was successful and Intervention 2: 2008 UK pounds
patient had no residual Ultrasound-guided foam Intervention 6 was extendedly dominated
varicosities (2) veins sclerotherapy and intervention 8 was dominated.
Cost components
were occluded but Intervention 3: incorporated:
there remain residual Endovenous laser ablation Costs of catheter and Intervention 5 was the cost-effective strategy
varicosities, and (3) (local anaesthesia) generator, staff, with a probability of 0.29. Intervention 3 had
there is residual reflux Intervention 4: ultrasonography, outpatient a probability of being the cost-effective
or incomplete
Radiofrequency ablation visits and sclerosant option of 0.35, and Intervention 4 had a
occlusion. Thereafter,
(local anaesthesia) probability of 0.24.
the model considers
the recurrence of vein Intervention 5:
reflux but not the Surgery (day case) Analysis of uncertainty:
recurrence of Intervention 6: One-way sensitivity analysis was conducted
varicosities. Endovenous laser ablation by varying: (1) the costs of treatments (2)
(general anaesthesia) estimates of relative treatment effectiveness
Perspective: UK NHS Intervention 7: with regards to saphenous vein reflux and
residual varicosities and (3) the correlation
M. S. Gohel, D. M. Epstein, and A. H. Davies. Cost-effectiveness of traditional and endovenous treatments for varicose veins. Br.J.Surg. 97 (12):1815-1823, 2010.
Time horizon: 5 years Radiofrequency ablation between the risks of incomplete vein
Treatment effect (general anaesthesia) occlusion after treatment and residual
duration: 5 years Intervention 8: varicosities.
Discounting: Costs Surgery (in patient)
=3.5% ; Outcomes = The results changed significantly from the
3.5% base case in the following instances. If the
odds ratio for re-intervention for residual
varicosities after sequential versus
concomitant phlebectomy was 5.50,
radiofrequency ablation (under local
anaesthesia) and endovenous laser ablation
(under local anaesthesia) are equally likely to
be cost effective and day-case surgery is
dominated.
Data sources
Health outcomes: Some outcomes were taken from clinical trials whilst other outcomes were informed by meta-analytic studies. The probability of complete/
287
275
successful occlusion following surgical ligation and stripping, for instance, was informed by the results of the clinical trial van den Bos et al. 2008 ; and the relative
risks of retreatment for residual varicosities after sequential versus concomitant phlebectomy was taken from results of the randomized controlled study Carradice et
46
al. 2009 . The odds ratio of incomplete occlusion following stripping surgery versus sclerotherapy, on the other hand, was informed by the meta-analysis Wright et al.
286
2006 .
219 224 170
Quality-of-life weights: EQ5D-derived HRQoL scores and profile based on Rasmussen et al. 2007 , Rautio et al. 2002 and Michaels et al. 2006 .
Cost sources: 2008-2009 UK NHS Reference costs, published drug and device manufacturer’s list prices (for 2008-2009).
Comments
Source of funding: European Venous Forum Group, which is partly funded by the pharmaceutical industry; Limitations: Modelling was undertaken over a 5 year
horizon, yet the costs and health outcomes associated with recurrence of varicosities are not considered beyond the first 3 months. All treatments of residual
varicosities with ultrasound-guided foam sclerotherapy at 3 months are assumed to be successful.
Overall applicability*: Directly applicable Overall quality**: Potentially serious limitations
1 Abbreviations: CI = confidence interval; CUA = cost-utility analysis; d/a deterministic analysis ICER = incremental cost-effectiveness ratio; NR = not reported; pa = probabilistic analysis; *
2 Directly applicable / Partially applicable / Not applicable; ** Minor limitations /Potentially serious Limitations / Very serious limitations
3
Forest plots
1 Appendix I: Forest plots

2 I.1 Chapter 7 – assessment for treatment
3 I.1.1 Diagnostic accuracy of hand held doppler
Figure 26: Diagnostic accuracy of hand held Doppler (threshold 0.5 seconds) vs. Duplex
(threshold 1 second): Sapheno-femoral junction
Study TP FP FN TN Sensitivity Specificity Sensitivity Specificity
Kent 1998 70 3 5 30 0.93 [0.85, 0.98] 0.91 [0.76, 0.98]
Kim 2000 36 9 1 24 0.97 [0.86, 1.00] 0.73 [0.54, 0.87]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
Figure 27: Diagnostic accuracy of hand held Doppler (threshold 1 second) vs. Duplex (threshold 1
second): Sapheno-femoral junction
Figure 28: Diagnostic accuracy of hand held Doppler (threshold 0.5 second) vs. Duplex (threshold
0.5 second): Sapheno-femoral junction
Mercer 1998 43 2 16 28 0.73 [0.60, 0.84] 0.93 [0.78, 0.99]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
Figure 29: Diagnostic accuracy of hand held Doppler (threshold unknown) vs. Duplex (threshold
unknown): Sapheno-femoral junction
DePalma 1993 24 5 26 25 0.48 [0.34, 0.63] 0.83 [0.65, 0.94]
Salaman 1995 49 1 4 18 0.92 [0.82, 0.98] 0.95 [0.74, 1.00]
Van der Heijden 1993 45 1 2 20 0.96 [0.85, 0.99] 0.95 [0.76, 1.00]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
1 second): Sapheno-popliteal junction
Kent 1998 14 18 3 73 0.82 [0.57, 0.96] 0.80 [0.71, 0.88]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
second): Sapheno-popliteal junction

288
Forest plots
0.5 second): Sapheno-popliteal junction
Mercer 1998 20 4 6 59 0.77 [0.56, 0.91] 0.94 [0.85, 0.98]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
unknown): Sapheno-popliteal junction
Salaman 1995 10 6 8 50 0.56 [0.31, 0.78] 0.89 [0.78, 0.96]
Van der Heijden 1993 17 0 0 51 1.00 [0.80, 1.00] 1.00 [0.93, 1.00]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
1 second): Great Saphenous Vein
Kent 1998 79 8 4 17 0.95 [0.88, 0.99] 0.68 [0.46, 0.85]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
second): Great Saphenous Vein
unknown): Great Saphenous Vein
Darke 1997 83 0 4 13 0.95 [0.89, 0.99] 1.00 [0.75, 1.00]
Van der Heijden 1993 41 1 4 22 0.91 [0.79, 0.98] 0.96 [0.78, 1.00]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
unknown): Short Saphenous Vein
Darke 1997 19 5 2 74 0.90 [0.70, 0.99] 0.94 [0.86, 0.98]
Van der Heijden 1993 16 0 2 50 0.89 [0.65, 0.99] 1.00 [0.93, 1.00]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
1 second): Perforators
Kent 1998 13 69 2 24 0.87 [0.60, 0.98] 0.26 [0.17, 0.36]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1

289
Forest plots
Figure 39: Diagnostic accuracy of hand held Doppler (threshold 0.5 second)vs. Duplex (threshold
0.5 second): Perforators
Mercer 1998 18 8 17 46 0.51 [0.34, 0.69] 0.85 [0.73, 0.93]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
unknown): Perforators
Salaman 1995 2 13 5 54 0.29 [0.04, 0.71] 0.81 [0.69, 0.89]
Van der Heijden 1993 10 1 9 17 0.53 [0.29, 0.76] 0.94 [0.73, 1.00]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
1 second): Popliteal veins
Kent 1998 7 9 7 84 0.50 [0.23, 0.77] 0.90 [0.82, 0.95]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
unknown): Popliteal veins
Salaman 1995 2 1 3 68 0.40 [0.05, 0.85] 0.99 [0.92, 1.00]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
second): Popliteal fossa
Campbell 1997 28 8 11 74 0.72 [0.55, 0.85] 0.90 [0.82, 0.96]
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
1 I.1.2 Duplex assessment prior to interventional treatment
Figure 44: Duplex prior to treatment vs. no duplex: patient–assessed symptoms - Operated limbs
unchanged or worse
Duplex No duplex Risk Ratio Risk Ratio
Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI
1.1.1 2 years
Blomgren 2006A 15 130 19 120 100.0% 0.73 [0.39, 1.37]
Subtotal (95% CI) 130 120 100.0% 0.73 [0.39, 1.37]
Total events 15 19
Heterogeneity: Not applicable
Test for overall effect: Z = 0.98 (P = 0.32)
1.1.2 7 years
Blomgren 2011 16 123 28 108 100.0% 0.50 [0.29, 0.88]
Subtotal (95% CI) 123 108 100.0% 0.50 [0.29, 0.88]
Total events 16 28
0.01 0.1 1 10 100

Favours duplex Favours no duplex

290
Forest plots
Figure 45: Duplex prior to treatment vs. no duplex: SFJ reflux

1.2.1 6-8 weeks
Blomgren 2005 10 160 37 166 97.4% 0.28 [0.14, 0.54]
Smith 2002 1 92 1 97 2.6% 1.05 [0.07, 16.61]
Subtotal (95% CI) 252 263 100.0% 0.30 [0.16, 0.57]
Total events 11 38
Heterogeneity: Chi² = 0.84, df = 1 (P = 0.36); I² = 0%
1.2.2 2 years
Blomgren 2005 14 127 44 129 100.0% 0.32 [0.19, 0.56]
Subtotal (95% CI) 127 129 100.0% 0.32 [0.19, 0.56]
Total events 14 44
Test for overall effect: Z = 4.03 (P < 0.0001)
1.2.3 7 years
Blomgren 2011 11 95 38 99 100.0% 0.30 [0.16, 0.55]
Subtotal (95% CI) 95 99 100.0% 0.30 [0.16, 0.55]
Total events 11 38
0.01 0.1 1 10 100

Figure 46: Duplex prior to treatment vs. no duplex: SPJ reflux

1.3.1 8 weeks
Blomgren 2005 4 160 9 166 100.0% 0.46 [0.14, 1.47]
Subtotal (95% CI) 160 166 100.0% 0.46 [0.14, 1.47]
Total events 4 9
1.3.2 2 years
Blomgren 2005 7 127 13 129 100.0% 0.55 [0.23, 1.33]
Subtotal (95% CI) 127 129 100.0% 0.55 [0.23, 1.33]
Total events 7 13
1.3.3 7 years
Blomgren 2011 2 95 9 99 100.0% 0.23 [0.05, 1.04]
Subtotal (95% CI) 95 99 100.0% 0.23 [0.05, 1.04]
Total events 2 9
0.01 0.1 1 10 100


291
Forest plots
Figure 47: Duplex prior to treatment vs. no duplex: GSV reflux

1.4.1 12 months
Smith 2002 8 92 9 97 100.0% 0.94 [0.38, 2.33]
Subtotal (95% CI) 92 97 100.0% 0.94 [0.38, 2.33]
Total events 8 9
0.01 0.1 1 10 100

Figure 48: Duplex prior to treatment vs. no duplex: SSV reflux

1.5.1 6 weeks
Smith 2002 4 92 6 97 100.0% 0.70 [0.20, 2.41]
Subtotal (95% CI) 92 97 100.0% 0.70 [0.20, 2.41]
Total events 4 6
1.5.2 12 months
Smith 2002 6 92 8 97 100.0% 0.79 [0.29, 2.19]
Subtotal (95% CI) 92 97 100.0% 0.79 [0.29, 2.19]
Total events 6 8
0.01 0.1 1 10 100

Favours experimental Favours control
Figure 49: Duplex prior to treatment vs. no duplex: Perforators reflux

1.6.1 6 weeks
Smith 2002 1 92 5 97 100.0% 0.21 [0.03, 1.77]
Subtotal (95% CI) 92 97 100.0% 0.21 [0.03, 1.77]
Total events 1 5
1.6.2 12 months
Smith 2002 4 92 15 97 100.0% 0.28 [0.10, 0.82]
Subtotal (95% CI) 92 97 100.0% 0.28 [0.10, 0.82]
Total events 4 15
0.01 0.1 1 10 100


292
Forest plots
Figure 50: Duplex prior to treatment vs. no duplex: Development of new branch varicosities at 1
year
Smith 2002 8 92 9 97 100.0% 0.94 [0.38, 2.33]
Total (95% CI) 92 97 100.0% 0.94 [0.38, 2.33]

Total events 8 9
0.01 0.1 1 10 100
Test for overall effect: Z = 0.14 (P = 0.89) Favours duplex Favours no duplex
Figure 51: Duplex prior to treatment vs. no duplex: Need for, or actual, re-operation
1.8.1 2 years
Blomgren 2005 3 145 14 147 100.0% 0.22 [0.06, 0.74]
Subtotal (95% CI) 145 147 100.0% 0.22 [0.06, 0.74]
Total events 3 14
1.8.2 7 years
Blomgren 2011 15 124 38 134 100.0% 0.43 [0.25, 0.74]
Subtotal (95% CI) 124 134 100.0% 0.43 [0.25, 0.74]
Total events 15 38
0.01 0.1 1 10 100

Figure 52: Duplex prior to treatment vs. no duplex: Adverse events - DVT
Blomgren 2005 0 145 0 147 Not estimable
Total (95% CI) 145 147 Not estimable

Total events 0 0
0.01 0.1 1 10 100
Test for overall effect: Not applicable Favours duplex Favours no duplex
Figure 53: Duplex prior to treatment vs. no duplex: Complications of varicose veins at 7 years –
venous ulcer
Blomgren 2011 0 70 0 88 Not estimable

Total events 0 0
0.01 0.1 1 10 100
Test for overall effect: Not applicable Favours duplex Favours no duplex

293
Forest plots
Figure 54: Duplex prior to treatment vs. no duplex: Complications of varicose veins at 7 years –
pigmentation/eczema
Blomgren 2011 3 70 9 88 100.0% 0.42 [0.12, 1.49]
Total (95% CI) 70 88 100.0% 0.42 [0.12, 1.49]

Total events 3 9
0.1 0.2 0.5 1 2 5 10
Test for overall effect: Z = 1.34 (P = 0.18) Favours duplex Favours no duplex
1 I.2 Chapter 8 – conservative management

2 I.2.1 Compression vs. no treatment/lifestyle advice
Figure 55: Compression vs. no treatment/lifestyle advice: numbers with pain or no improvement
at end of treatment
Compression Control Risk Ratio Risk Ratio
Study or Subgroup Events Total Events Total Weight M-H, Random, 95% CI M-H, Random, 95% CI
Benigni 2003 27 61 37 53 64.6% 0.63 [0.45, 0.88]
Krijnen 1997 2 30 12 34 35.4% 0.19 [0.05, 0.78]
Total (95% CI) 91 87 100.0% 0.41 [0.12, 1.40]

Total events 29 49
Heterogeneity: Tau² = 0.57; Chi² = 3.08, df = 1 (P = 0.08); I² = 67%
0.01 0.1 1 10 100
Test for overall effect: Z = 1.42 (P = 0.15) Favours compression Favours control
Figure 56: Compression vs. no treatment/lifestyle advice: pain levels (VAS) at the end of
treatment (better indicated by lower values). SMD used as scale of VAS unclear in both
studies.
Figure 57: Compression vs. no treatment/lifestyle advice: numbers with heavy or tired legs or no
improvement in heavy or tired legs at end of treatment
Benigni 2003 20 59 35 54 68.4% 0.52 [0.35, 0.79]
Krijnen 1997 8 30 18 34 31.6% 0.50 [0.26, 0.99]
Total (95% CI) 89 88 100.0% 0.52 [0.36, 0.73]

Total events 28 53
0.01 0.1 1 10 100

294
Forest plots
Figure 58: Compression vs. no treatment/lifestyle advice: heavy or tired legs (VAS) at end of
treatment (better indicated by lower values)
Compression Control Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI IV, Fixed, 95% CI
Anderson 1990 34.1 30.9 66 36.3 28.4 66 100.0% -2.20 [-12.33, 7.93]
Total (95% CI) 66 66 100.0% -2.20 [-12.33, 7.93]

-50 -25 0 25 50
Figure 59: Compression vs. no treatment/lifestyle advice: numbers with no improvement in

cramps at end of treatment
Benigni 2003 37 61 44 55 100.0% 0.76 [0.60, 0.97]
Total (95% CI) 61 55 100.0% 0.76 [0.60, 0.97]

Total events 37 44
0.5 0.7 1 1.5 2
Figure 60: Compression vs. no treatment/lifestyle advice: night cramps level (VAS) at end of
treatment (better indicated by lower values)
Anderson 1990 22.4 25.2 66 24.9 24.4 66 100.0% -2.50 [-10.96, 5.96]
Total (95% CI) 66 66 100.0% -2.50 [-10.96, 5.96]

-20 -10 0 10 20
Figure 61: Compression vs. no treatment/lifestyle advice: numbers of patients reporting no

improvement in ankle swelling at end of treatment
Benigni 2003 35 61 43 53 100.0% 0.71 [0.55, 0.91]
Total (95% CI) 61 53 100.0% 0.71 [0.55, 0.91]

Total events 35 43
0.5 0.7 1 1.5 2
Figure 62: Compression vs. no treatment/lifestyle advice: self-reported swelling levels (VAS) at
end of treatment (better indicated by lower values)
Anderson 1990 28.2 29.25 66 35.3 30.1 66 100.0% -7.10 [-17.23, 3.03]
Total (95% CI) 66 66 100.0% -7.10 [-17.23, 3.03]

-100 -50 0 50 100

295
Forest plots
Figure 63: Compression vs. no treatment/lifestyle advice body image dissatisfaction (VAS) at end
of treatment (better indicated by lower values)
Anderson 1990 43.2 37.4 66 41.1 38.2 66 100.0% 2.10 [-10.80, 15.00]
Total (95% CI) 66 66 100.0% 2.10 [-10.80, 15.00]

-100 -50 0 50 100
Figure 64: Compression vs. no treatment/lifestyle advice: numbers reporting fewer complaints
compression control Risk Ratio Risk Ratio
Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI Year M-H, Fixed, 95% CI
Krijnen 1997 17 30 4 34 100.0% 4.82 [1.82, 12.73] 1997
Total (95% CI) 30 34 100.0% 4.82 [1.82, 12.73]

Total events 17 4
0.1 0.2 0.5 1 2 5 10
Test for overall effect: Z = 3.17 (P = 0.002) Favours control Favours compression
2 I.2.2 Compression vs. interventional treatment
3 I.2.2.1 Compression vs. surgery
Figure 65: Compression vs. surgery: quality of life (higher score indicates better outcome)
Surgery Compression Mean Difference Mean Difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI
1.5.1 SF-6D 1 year
Micheals 2006A 0.77 0.1 75 0.73 0.11 98 100.0% 0.04 [0.01, 0.07] 2006
Subtotal (95% CI) 75 98 100.0% 0.04 [0.01, 0.07]
1.5.2 SF-6D 2 years

Micheals 2006A 0.78 0.1 44 0.72 0.13 47 100.0% 0.06 [0.01, 0.11] 2006
Subtotal (95% CI) 44 47 100.0% 0.06 [0.01, 0.11]
1.5.3 EQ-5D 1 year

Micheals 2006A 0.87 0.14 78 0.78 0.18 101 100.0% 0.09 [0.04, 0.14] 2006
Subtotal (95% CI) 78 101 100.0% 0.09 [0.04, 0.14]
1.5.4 EQ-5D 2 years

Micheals 2006A 0.84 0.21 34 0.85 0.17 44 100.0% -0.01 [-0.10, 0.08] 2006
Subtotal (95% CI) 34 44 100.0% -0.01 [-0.10, 0.08]
-0.1 -0.05 0 0.05 0.1

Favours compression Favours surgery

296
Forest plots
Figure 66: Compression vs. surgery: Patient assessed symptoms (proportion the same or worse)
Compression Surgery Risk Ratio Risk Ratio
1.6.1 aching at 1 yr
Micheals 2006A 72 97 15 75 100.0% 3.71 [2.33, 5.92]
Subtotal (95% CI) 97 75 100.0% 3.71 [2.33, 5.92]
Total events 72 15
1.6.2 heaviness at 1 year

Micheals 2006A 52 97 9 75 100.0% 4.47 [2.36, 8.47]
Subtotal (95% CI) 97 75 100.0% 4.47 [2.36, 8.47]
Total events 52 9
1.6.3 itching at 1 year

Micheals 2006A 42 97 10 75 100.0% 3.25 [1.75, 6.04]
Subtotal (95% CI) 97 75 100.0% 3.25 [1.75, 6.04]
Total events 42 10
1.6.4 swelling at 1 year

Micheals 2006A 31 97 8 75 100.0% 3.00 [1.46, 6.13]
Subtotal (95% CI) 97 75 100.0% 3.00 [1.46, 6.13]
Total events 31 8
1.6.5 cosmetic concerns at 1 year

Micheals 2006A 75 97 13 75 100.0% 4.46 [2.69, 7.40]
Subtotal (95% CI) 97 75 100.0% 4.46 [2.69, 7.40]
Total events 75 13
0.01 0.1 1 10 100

Favours compression Favours surgery
Figure 67: Compression vs. surgery: Adverse events – neural injury/damage

Favours compression surgery Risk Ratio Risk Ratio
Micheals 2006A 0 122 1 124 100.0% 0.34 [0.01, 8.24]
Total (95% CI) 122 124 100.0% 0.34 [0.01, 8.24]

Total events 0 1
0.01 0.1 1 10 100
Test for overall effect: Z = 0.66 (P = 0.51) Favours compression Favours surgery
Figure 68: Compression vs. surgery: Patient dissatisfaction at 1 year

compression surgery Risk Ratio Risk Ratio
Micheals 2006A 53 107 3 65 100.0% 10.73 [3.50, 32.94]
Total (95% CI) 107 65 100.0% 10.73 [3.50, 32.94]

Total events 53 3
0.01 0.1 1 10 100
Test for overall effect: Z = 4.15 (P < 0.0001) Favours compression Favours surgery

297
Forest plots
1 I.3 Chapter 9 – interventional treatment

2 I.3.1 Stripping surgery vs. foam sclerotherapy
Figure 69: Stripping surgery vs. foam sclerotherapy:SF-36 Physical 4 weeks
Figure 70: Stripping surgery vs. foam sclerotherapy:SF-36 Physical 1 year
Figure 71: Stripping surgery vs. foam sclerotherapy: SF-36 mental 4 weeks
Figure 72: Stripping surgery vs. foam sclerotherapy: SF-36 mental 1 year
Figure 73: Stripping surgery vs. foam sclerotherapy: Patient- assessed outcomes: EQ-5D change
from baseline to 2 years (higher better)

298
Forest plots
Figure 74: Stripping surgery vs. foam sclerotherapy: Patient-assessed symptoms: Pain due to
varicose veins (subscale from SF-36)
Sclerotherapy Stripping Mean Difference Mean Difference
2.1.1 foam
Rasmussen et al, 2011 85.11 23.45 124 88.77 17.11 124 100.0% -3.66 [-8.77, 1.45] 2011
Subtotal (95% CI) 124 124 100.0% -3.66 [-8.77, 1.45]
-10 -5 0 5 10
Favours stripping Favours sclerotherapy
Figure 75: Stripping surgery vs. foam sclerotherapy: Patient-assessed symptoms: worsening of
symptoms at 2 years

299
Forest plots
symptoms at 1 year
symptoms at 3 months
2
3

300
Forest plots
Figure 78: Stripping surgery vs. foam sclerotherapy: Physician-reported outcomes: overall VCSS
score change from baseline by 2 years
Figure 79: Stripping surgery vs. foam sclerotherapy: Physician-reported outcomes: VCSS pain
Stripping Sclerotherapy Mean Difference Mean Difference
3.10.1 1 month
Figuerido 2009 0.93 0.53 29 0.89 0.51 27 100.0% 0.04 [-0.23, 0.31] 2009
Subtotal (95% CI) 29 27 100.0% 0.04 [-0.23, 0.31]
3.10.2 2 months
Figuerido 2009 0.79 0.49 29 0.59 0.5 27 100.0% 0.20 [-0.06, 0.46] 2009
Subtotal (95% CI) 29 27 100.0% 0.20 [-0.06, 0.46]
3.10.3 6 months
Figuerido 2009 0.72 0.53 29 0.56 0.51 27 100.0% 0.16 [-0.11, 0.43] 2009
Subtotal (95% CI) 29 27 100.0% 0.16 [-0.11, 0.43]
-0.5 -0.25 0 0.25 0.5

Figure 80: Stripping surgery vs. foam sclerotherapy: Physician-reported outcomes: VCSS oedema
3.11.1 1 month
Figuerido 2009 0.69 0.6 29 0.7 0.54 27 100.0% -0.01 [-0.31, 0.29]
Subtotal (95% CI) 29 27 100.0% -0.01 [-0.31, 0.29]
3.11.2 2 months
Figuerido 2009 0.59 0.63 29 0.56 0.64 27 100.0% 0.03 [-0.30, 0.36]
Subtotal (95% CI) 29 27 100.0% 0.03 [-0.30, 0.36]
3.11.3 6 months
Figuerido 2009 0.55 0.63 29 0.48 0.64 27 100.0% 0.07 [-0.26, 0.40]
Subtotal (95% CI) 29 27 100.0% 0.07 [-0.26, 0.40]
-0.5 -0.25 0 0.25 0.5


301
Forest plots
Figure 81: Stripping surgery vs. foam sclerotherapy: Physician-reported outcomes: VCSS
inflammation
3.12.1 1 month
Figuerido 2009 0.76 0.44 29 0.89 0.32 27 100.0% -0.13 [-0.33, 0.07] 2009
Subtotal (95% CI) 29 27 100.0% -0.13 [-0.33, 0.07]
3.12.2 2 months
Figuerido 2009 0.72 0.45 29 0.89 0.32 27 100.0% -0.17 [-0.37, 0.03] 2009
Subtotal (95% CI) 29 27 100.0% -0.17 [-0.37, 0.03]
3.12.3 6 months
Figuerido 2009 0.72 0.45 29 0.89 0.32 27 100.0% -0.17 [-0.37, 0.03] 2009
Subtotal (95% CI) 29 27 100.0% -0.17 [-0.37, 0.03]
-0.5 -0.25 0 0.25 0.5

Figure 82: Stripping surgery vs. foam sclerotherapy: Presence of reflux within 3 months

302
Forest plots
Figure 83: Stripping surgery vs. foam sclerotherapy: Presence of reflux >3–12 months
Figure 84: Stripping surgery vs. foam sclerotherapy: Presence of reflux >1-5 years
Figure 85: Stripping surgery vs. foam sclerotherapy: Need for further treatment from >3–12
months
Stripping surgery Sclerotherapy Risk Ratio Risk Ratio
4.7.1 crossectomy used with sclerotherapy
Bountouroglou 2006 2 28 4 30 100.0% 0.54 [0.11, 2.70]
Subtotal (95% CI) 28 30 100.0% 0.54 [0.11, 2.70]
Total events 2 4
0.05 0.2 1 5 20

303
Forest plots
Figure 86: Stripping surgery vs. foam sclerotherapy: Major neurological event
stripping surgery sclerotherapy Risk Ratio Risk Ratio
Kalodiki 2011 0 43 0 39 Not estimable
Subtotal (95% CI) 43 39 Not estimable
Total events 0 0
Test for overall effect: Not applicable
0.01 0.1 1 10 100

Figure 87: Stripping surgery vs. foam sclerotherapy: Adverse events from intervention: Phlebitis
Figure 88: Stripping surgery vs. foam sclerotherapy: Adverse events from intervention: PE

304
Forest plots
Figure 89: Stripping surgery vs. foam sclerotherapy: Adverse events from intervention: DVT
Figure 90: Stripping surgery vs. foam sclerotherapy: Adverse events from intervention: Nerve
injury/damage - with crossectomy
stripping surgery sclerotherapy Peto Odds Ratio Peto Odds Ratio
Study or Subgroup Events Total Events Total Weight Peto, Fixed, 95% CI Year Peto, Fixed, 95% CI
Kalodiki 2011 2 43 0 39 50.1% 6.90 [0.42, 112.53] 2011
Liu 2011 2 30 0 29 49.9% 7.40 [0.45, 121.22] 2011
Subtotal (95% CI) 73 68 100.0% 7.14 [0.99, 51.52]
Total events 4 0
0.001 0.1 1 10 1000

Favours Stripping Surgery Favours Sclerotherapy
Figure 91: Stripping surgery vs. foam sclerotherapy: Adverse events from intervention: Nerve
injury/damage - no crossectomy

305
Forest plots
Figure 92: Stripping surgery vs. foam sclerotherapy: Adverse events from intervention: Skin
discolouration/hyper pigmentation
Figure 93: Stripping surgery vs. foam sclerotherapy: Adverse events from intervention: Post
procedure pain
stripping surgery sclerotherapy Risk Ratio Risk Ratio
Abela et al, 2008 48 60 7 30 53.4% 3.43 [1.77, 6.64] 2008
Liu 2011 24 30 8 29 46.6% 2.90 [1.57, 5.37] 2011
Subtotal (95% CI) 90 59 100.0% 3.18 [2.01, 5.03]
Total events 72 15
5.8.2 no crossectomy used with sclerotherapy

Wright et al, 2006 39 94 73 178 100.0% 1.01 [0.75, 1.36] 2006
Subtotal (95% CI) 94 178 100.0% 1.01 [0.75, 1.36]
Total events 39 73
0.001 0.1 1 10 1000

Favours stripping surgery Favours sclerotherapy
Figure 94: Stripping surgery vs. foam sclerotherapy: Adverse events from intervention: Post
procedure pain VAS 1-10
stripping surgery sclerotherapy Mean Difference Mean Difference
5.8.1 no crossectomy used with sclerotherapy
Rasmussen et al, 2011 2.25 2.23 135 1.6 2.04 144 100.0% 0.65 [0.15, 1.15]
Subtotal (95% CI) 135 144 100.0% 0.65 [0.15, 1.15]
-2 -1 0 1 2
Favours stripping surgery Favours sclerotherapy

306
Forest plots
1 I.3.2 Stripping surgery vs. endothermal ablation
2 I.3.2.1 Primary varicose veins
Figure 95: Stripping surgery vs. endothermal ablation in primary VV: SF-36 Physical 4 weeks
Figure 96: Stripping surgery vs. endothermal ablation in primary VV: SF-36 mental 4 weeks
Figure 97: Stripping surgery vs. endothermal ablation in primary VV:SF-36 Physical 1 year

307
Forest plots
Figure 98: Stripping surgery vs. endothermal ablation in primary VV: SF-36 mental 1 year
Figure 99: Stripping surgery vs. endothermal ablation in primary VV: Global quality of life – follow-
up 1-12 weeks, 1 year and 2 years
3 [ Note that Subramonia 2010 used AVVQ, whilst Rass 2012 and Lurie 2003 used CIVIQ -2 – hence the use of standardised
4 mean differences]

308
Forest plots
1 Figure 100: Stripping surgery vs. endothermal ablation in primary VV: Patient reported
2 symptoms – oedema and pain (dichotomous)
Endothermal Stripping Risk Ratio Risk Ratio
1.9.2 oedema
Pronk 2010 6 56 10 62 100.0% 0.66 [0.26, 1.71]
Subtotal (95% CI) 56 62 100.0% 0.66 [0.26, 1.71]
Total events 6 10
1.9.4 pain
Pronk 2010 1 56 6 62 100.0% 0.18 [0.02, 1.49]
Subtotal (95% CI) 56 62 100.0% 0.18 [0.02, 1.49]
Total events 1 6
0.01 0.1 1 10 100

Favours endothermal Favours stripping
3 Figure 101: Stripping surgery vs. endothermal ablation in primary VV: dissatisfaction with body
4 image
6 Figure 102: Stripping surgery vs. endothermal ablation in primary VV: Physician reported
7 disease severity (post-test; continuous)

309
Forest plots
Figure 103: Stripping surgery vs. endothermal ablation in primary VV: Physician reported
disease severity (change from baseline; continuous)
Endothermal Stripping Mean Difference Mean Difference
1.10.1 change from baseline (VCSS) <50 days
Rautio 2002 -5.1 1.5 15 -4.4 1.1 13 100.0% -0.70 [-1.67, 0.27]
Subtotal (95% CI) 15 13 100.0% -0.70 [-1.67, 0.27]
1.10.2 change from baseline (VCSS) 3 years

Perala 2005 -4.3 2.3 15 -4 1.2 13 100.0% -0.30 [-1.63, 1.03]
Subtotal (95% CI) 15 13 100.0% -0.30 [-1.63, 1.03]
-4 -2 0 2 4
3 Figure 104: stripping surgery vs. endothermal ablation in primary VV: Physician reported
4 disease severity (dichotomous)
Endothermal Stripping Risk Ratio Risk Ratio
1.12.1 1 week FU
Lurie 2005 8 43 6 36 100.0% 1.12 [0.43, 2.92]
Subtotal (95% CI) 43 36 100.0% 1.12 [0.43, 2.92]
Total events 8 6
1.12.4 1-2 year FU

Lurie 2005 9 36 12 29 43.5% 0.60 [0.30, 1.23]
Pronk 2010 17 56 18 61 56.5% 1.03 [0.59, 1.79]
Subtotal (95% CI) 92 90 100.0% 0.84 [0.55, 1.30]
Total events 26 30
0.05 0.2 1 5 20
5 Figure 105: Stripping surgery vs. endothermal ablation in primary VV: Physician reported
6 disease severity (dichotomous) – asymptomatic according to VDS
10

310
Forest plots
1 Figure 106: Stripping surgery vs. endothermal ablation in primary VV: GSV reflux

311
Forest plots
Figure 107: Stripping surgery vs. endothermal ablation in primary VV: Adverse events – post
op pain (dichotomous
Figure 108: Stripping surgery vs. endothermal ablation in primary VV: Adverse events - Post op
pain (continuous variable)
1.25.1 1 day laser
Pronk 2010 3.58 2.6 62 4 2.34 68 100.0% -0.42 [-1.27, 0.43]
Subtotal (95% CI) 62 68 100.0% -0.42 [-1.27, 0.43]
1.25.5 10-14days laser

Pronk 2010 1.66 2.04 62 0.77 1.46 68 45.1% 0.89 [0.27, 1.51]
Rasmussen 2011 2.58 2.41 143 2.25 2.23 123 54.9% 0.33 [-0.23, 0.89]
Subtotal (95% CI) 205 191 100.0% 0.58 [0.17, 1.00]
1.25.7 10-14 days RF

Rasmussen 2011 1.21 1.72 146 2.25 2.23 123 70.7% -1.04 [-1.52, -0.56]
Rautio 2002 0.7 0.5 15 1.7 1.3 13 29.3% -1.00 [-1.75, -0.25]
Subtotal (95% CI) 161 136 100.0% -1.03 [-1.43, -0.62]
-4 -2 0 2 4

312
Forest plots
Figure 109: Stripping surgery vs. endothermal ablation in primary VV: Adverse events –
phlebitis/thrombophlebitis
Figure 110: Stripping surgery vs. endothermal ablation in primary VV: Adverse events –
sensory deficits/neural injury

313
Forest plots
Figure 111: Stripping surgery vs. endothermal ablation in primary VV: Adverse events - DVT
Figure 112: Stripping surgery vs. endothermal ablation in primary VV: Adverse events – limb
discolouration
Figure 113: Stripping surgery vs. endothermal ablation in primary VV: Return to normal
activities by endothermal type
1.20.1 RF
Lurie 2003 1.36 0.92 44 6.65 6.76 36 8.5% -5.29 [-7.51, -3.07] 2003
ElKaffas 2011 3 3 90 7 2.6 90 62.4% -4.00 [-4.82, -3.18] 2011
Subtotal (95% CI) 134 126 70.8% -4.15 [-4.92, -3.38]
1.20.2 Laser
Rasmussen 2007 6.9 7 69 7.7 6.1 68 8.7% -0.80 [-3.00, 1.40] 2007
Pronk 2010 3.2 4.3 62 3.2 4 68 20.5% 0.00 [-1.43, 1.43] 2010
Subtotal (95% CI) 131 136 29.2% -0.24 [-1.44, 0.96]
Total (95% CI) 265 262 100.0% -3.01 [-3.66, -2.36]

Heterogeneity: Chi² = 30.50, df = 3 (P < 0.00001); I² = 90%
-10 -5 0 5 10
Test for overall effect: Z = 9.12 (P < 0.00001) Favours endothermal Favours stripping
Test for subgroup differences: Chi² = 29.00, df = 1 (P < 0.00001), I² = 96.6%

314
Forest plots
Figure 114: Stripping surgery vs. endothermal ablation in primary VV: Return to work by
endothermal type
1.22.1 RF
Rautio 2002 6.5 3.3 15 15.6 6 13 9.3% -9.10 [-12.76, -5.44] 2002
Lurie 2003 4.7 11.86 44 12.4 11.59 36 4.7% -7.70 [-12.86, -2.54] 2003
Subtotal (95% CI) 59 49 14.1% -8.63 [-11.62, -5.64]
1.22.2 Laser
Rasmussen 2007 7 6 69 7.6 4.9 68 37.3% -0.60 [-2.43, 1.23] 2007
Pronk 2010 4.4 5.4 62 4.2 3.7 68 48.6% 0.20 [-1.41, 1.81] 2010
Subtotal (95% CI) 131 136 85.9% -0.15 [-1.36, 1.06]
Total (95% CI) 190 185 100.0% -1.34 [-2.46, -0.22]

Heterogeneity: Chi² = 27.22, df = 3 (P < 0.00001); I² = 89%
-10 -5 0 5 10
Test for overall effect: Z = 2.34 (P = 0.02) Favours endothermal Favours stripping
Test for subgroup differences: Chi² = 26.62, df = 1 (P < 0.00001), I² = 96.2%
3 I.3.2.2 Recurrent varicose veins
Figure 115: Stripping surgery vs. endothermal ablation in recurrent VV: GSV reflux – 6 weeks
Figure 116: Stripping surgery vs. endothermal ablation in recurrent VV:Adverse events –
thrombophlebitis (6 weeks)
Figure 117: Stripping surgery vs. endothermal ablation in recurrent VV:Adverse events –
sensory deficits / neural injury (neuralgia and numbness at 6 weeks)

315
Forest plots
Figure 118: Stripping surgery vs. endothermal ablation in recurrent VV: Adverse events –
infection (6 weeks)
Figure 119: Stripping surgery vs. endothermal ablation in recurrent VV: Adverse events -
oedema
2 I.3.3 Foam sclerotherapy vs. endothermal ablation
Figure 120: Foam sclerotherapy vs. endothermal ablation: SF-36 Physical 4 weeks
Figure 121: Foam sclerotherapy vs. endothermal ablation: SF-36 mental 4 weeks

316
Forest plots
Figure 122: Foam sclerotherapy vs. endothermal ablation: SF-36 Physical 1 year
Figure 123: Foam sclerotherapy vs. endothermal ablation: SF-36 mental 1 year

317
Forest plots
Figure 124: Foam sclerotherapy vs. endothermal ablation: Pain due to varicose veins (1 year)
(higher better as taken from SF-36 sub-scale)
Figure 125: Foam sclerotherapy vs. endothermal ablation: Reflux above knee at 3 days
Figure 126: Foam sclerotherapy vs. endothermal ablation (Laser):Reflux above knee at 3-4
weeks

318
Forest plots
Figure 127: Foam sclerotherapy vs. endothermal ablation (RF): Reflux above knee at 1 month
Figure 128: Foam sclerotherapy vs. endothermal ablation(Laser): Reflux above knee at 3
months
Figure 129: Foam sclerotherapy vs. endothermal ablation: Reflux above knee 1 year
Figure 130: Foam sclerotherapy vs. endothermal ablation: Reflux at 1 year observational data

319
Forest plots
Figure 131: Foam sclerotherapy vs. endothermal ablation: Reflux below knee 3 weeks
Figure 132: Foam sclerotherapy vs. endothermal ablation: Reflux below knee 3 months
Figure 133: Foam sclerotherapy vs. endothermal ablation: Adverse events – pain (VAS)
observational data
Figure 134: Foam sclerotherapy vs. endothermal ablation: Adverse events – post op pain 10
days

320
Forest plots
Figure 135: Foam sclerotherapy vs. endothermal ablation: Adverse events – DVT observational
data
Figure 136: Foam sclerotherapy vs. endothermal ablation: Adverse events – neural
injury/damage
Figure 137: Foam sclerotherapy vs. endothermal ablation: Adverse events – paraesthesia
observational data

321
Forest plots
Figure 138: Foam sclerotherapy vs. endothermal ablation: Adverse events PE
Figure 139: Foam sclerotherapy vs. endothermal ablation: Adverse events – Phlebitis
Figure 140: Foam sclerotherapy vs. endothermal ablation: Adverse events – Phlebitis
observational data

322
Forest plots
Figure 141: Foam sclerotherapy vs. endothermal ablation: Adverse events – hyper-
pigmentation
Figure 142: Foam sclerotherapy vs. endothermal ablation(Laser): Need for further treatment
2 I.3.4 Truncal treatment with tributary treatment vs. truncal treatment alone
Figure 143: Truncal + tributary vs. truncal alone: Reflux at one week
endo + tributary endo alone Risk Ratio Risk Ratio
1.1.1 SFJ 1 week
Carradice 2009 0 24 0 24 Not estimable
Total events 0 0
1.1.2 GSV 1 week

Carradice 2009 0 24 0 24 Not estimable
Total events 0 0
0.01 0.1 1 10 100

Favours endo + tributary Favours endo alone

323
Forest plots
Figure 144: Truncal + tributary vs. truncal alone: Adverse events - phlebitis
Carradice 2009 0 24 1 24 100.0% 0.33 [0.01, 7.80]
Total (95% CI) 24 24 100.0% 0.33 [0.01, 7.80]

Total events 0 1
0.01 0.1 1 10 100
Test for overall effect: Z = 0.68 (P = 0.49) Favours endo + tributary Favours endo alone
Figure 145: Truncal + tributary vs. truncal alone: Adverse events - pigmentation
endo + tributary endo alone Peto Odds Ratio Peto Odds Ratio
Study or Subgroup Events Total Events Total Weight Peto, Fixed, 95% CI Year Peto, Fixed, 95% CI
Carradice 2009 2 24 0 24 100.0% 7.72 [0.47, 127.14] 2009
Total (95% CI) 24 24 100.0% 7.72 [0.47, 127.14]

Total events 2 0
0.005 0.1 1 10 200
Favours endo + tributary Favours endo alone
Source: <Insert Source text here>
Figure 146: Truncal + tributary vs. truncal alone: Adverse events – thigh neuralgia
endo + tributary endo alone Peto Odds Ratio Peto Odds Ratio
Study or Subgroup Events Total Events Total Weight Peto, Fixed, 95% CI Peto, Fixed, 95% CI
Carradice 2009 1 24 0 24 100.0% 7.39 [0.15, 372.38]
Total (95% CI) 24 24 100.0% 7.39 [0.15, 372.38]

Total events 1 0
0.01 0.1 1 10 100
Figure 147: Truncal + tributary vs. truncal alone: Need for ambulatory phlebectomy at 6 weeks
Carradice 2009 1 25 16 24 100.0% 0.06 [0.01, 0.42]
Total (95% CI) 25 24 100.0% 0.06 [0.01, 0.42]

Total events 1 16
0.01 0.1 1 10 100

324
Forest plots
1 I.4 Chapter 10 – compression after interventional treatment

2 I.4.1.1 Compression after surgery vs. surgery alone
Figure 148: Compression after interventional treatment vs. interventional treatment alone:
adverse events – post operative pain (higher worse)
surg with comp surg alone Mean Difference Mean Difference
1.1.1 3 days
Houtermans-Auckel 2009 2.5 2.8 46 1.8 2.2 50 100.0% 0.70 [-0.31, 1.71] 2009
Subtotal (95% CI) 46 50 100.0% 0.70 [-0.31, 1.71]
1.1.2 2 weeks
Subtotal (95% CI) 46 50 100.0% 0.00 [-0.94, 0.94]
1.1.3 4 weeks
Subtotal (95% CI) 46 50 100.0% 0.30 [-0.19, 0.79]
-2 -1 0 1 2
Favours surg + comp Favours surg alone
adverse events - numbness
surg with comp surg alone Risk Ratio Risk Ratio
1.2.1 3 days
Houtermans-Auckel 2009 4 46 3 50 100.0% 1.45 [0.34, 6.13] 2009
Subtotal (95% CI) 46 50 100.0% 1.45 [0.34, 6.13]
Total events 4 3
1.2.2 2 weeks
Houtermans-Auckel 2009 0 46 2 50 100.0% 0.22 [0.01, 4.40] 2009
Subtotal (95% CI) 46 50 100.0% 0.22 [0.01, 4.40]
Total events 0 2
1.2.3 4 weeks
Houtermans-Auckel 2009 0 46 0 50 Not estimable 2009
Total events 0 0
0.01 0.1 1 10 100

Favours surg with comp Favours surg alone
return to work (days)
surg with comp surg alone Mean Difference Mean Difference
Houtermans-Auckel 2009 15 8.4 46 11 7.5 50 100.0% 4.00 [0.80, 7.20]
Total (95% CI) 46 50 100.0% 4.00 [0.80, 7.20]

-4 -2 0 2 4
Test for overall effect: Z = 2.45 (P = 0.01) Favours surg with comp Favours surg only

325
Forest plots
1 I.4.1.2 Compression after foam sclerotherapy vs. foam sclerotherapy alone
QoL – CIVIQ global score – change from baseline (greater negative change is better)
sclero + comp sclero alone Mean Difference Mean Difference
2.1.1 14 days
Hamel-Desnos 2010 -5.5 10 22 -9 9.9 21 100.0% 3.50 [-2.45, 9.45] 2010
Subtotal (95% CI) 22 21 100.0% 3.50 [-2.45, 9.45]
2.1.2 28 days
Hamel-Desnos 2010 -9.4 10 23 -11 14 24 100.0% 1.60 [-5.33, 8.53] 2010
Subtotal (95% CI) 23 24 100.0% 1.60 [-5.33, 8.53]
-10 -5 0 5 10
Favours sclero plus comp Favours sclero alone
reflux at 28 days
sclero + comp sclero alone Risk Ratio Risk Ratio
Hamel-Desnos 2010 0 31 0 29 Not estimable

Total events 0 0
0.01 0.1 1 10 100
Test for overall effect: Not applicable Favours sclero + comp Favours sclero alone
adverse events – major neurological events
Hamel-Desnos 2010 0 31 0 29 Not estimable 2010

Total events 0 0
0.01 0.1 1 10 100
Test for overall effect: Not applicable Favours sclero + comp Favours sclero alone
adverse events – visual disturbance (scotoma) resolving within 15 minutes
Hamel-Desnos 2010 0 31 1 29 100.0% 0.31 [0.01, 7.38]
Total (95% CI) 31 29 100.0% 0.31 [0.01, 7.38]

Total events 0 1
0.01 0.1 1 10 100
Test for overall effect: Z = 0.72 (P = 0.47) Favours sclero + comp Favours sclero alone

326
Forest plots
adverse events – moderate pain day 28
Hamel-Desnos 2010 1 30 3 29 100.0% 0.32 [0.04, 2.92]
Total (95% CI) 30 29 100.0% 0.32 [0.04, 2.92]

Total events 1 3
0.01 0.1 1 10 100
adverse events - pigmentation
Hamel-Desnos 2010 2 30 1 29 100.0% 1.93 [0.19, 20.18]
Total (95% CI) 30 29 100.0% 1.93 [0.19, 20.18]

Total events 2 1
0.01 0.1 1 10 100
adverse events - thrombophlebitis
Hamel-Desnos 2010 3 30 3 29 100.0% 0.97 [0.21, 4.41]
Total (95% CI) 30 29 100.0% 0.97 [0.21, 4.41]

Total events 3 3
0.01 0.1 1 10 100

327
Forest plots
patient assessed symptoms
2.8.1 heavy legs
Hamel-Desnos 2010 20 30 16 29 100.0% 1.21 [0.80, 1.83]
Subtotal (95% CI) 30 29 100.0% 1.21 [0.80, 1.83]
Total events 20 16
2.8.2 pain
Hamel-Desnos 2010 21 30 17 29 100.0% 1.19 [0.81, 1.76]
Subtotal (95% CI) 30 29 100.0% 1.19 [0.81, 1.76]
Total events 21 17
2.8.3 oedema
Hamel-Desnos 2010 15 30 15 29 100.0% 0.97 [0.59, 1.60]
Subtotal (95% CI) 30 29 100.0% 0.97 [0.59, 1.60]
Total events 15 15
2.8.4 paraesthesia
Hamel-Desnos 2010 17 30 13 29 100.0% 1.26 [0.76, 2.11]
Subtotal (95% CI) 30 29 100.0% 1.26 [0.76, 2.11]
Total events 17 13
2.8.5 cramp
Hamel-Desnos 2010 11 30 16 29 100.0% 0.66 [0.37, 1.18]
Subtotal (95% CI) 30 29 100.0% 0.66 [0.37, 1.18]
Total events 11 16
0.5 0.7 1 1.5 2

Favours scler + comp Favours scler alone

328
Excluded clinical studies
1 Appendix J: Excluded clinical studies

2
3 J.1 Chapter 5 – patient perceptions and expectations

4 Table 98: Studies excluded from the clinical review for chapter 5
Reference Reason for exclusion
31
Bradshaw 1999 Does not match the review question
56
Ching 2010 Only covered new Zealand-based websites and so not relevant to the UK
68
Davies 1995 Does not match the review question
179
Murphy 2001 This paper was deemed too old for its survey of internet information to have
any continued relevance.
235
Sains 2005 Does not match the review question
243
Scurr 2008 Does not match the review question
254
Srilekha 2005 Does not match the review question
6 J.2 Chapter 6 – referral to a vascular service

7 J.2.1 Risk factors associated with disease progression
8 Table 99: Studies excluded from the clinical review: risk factors associated with disease
9 progression
22
Bernardini, 2010 No relevant outcomes and also does not match review question
32
Brand, 1988 No relevant outcomes and also does not match review question
45
Carpentier, 2008 Abstract. Authors contacted for more information but no reply received.
58
Christenson, 2012 Abstract. Authors contacted for more information but no reply received.
63
Cushman, 2010 No relevant outcomes and also does not match review question
78
Diamond, 2012 No relevant outcomes and also does not match review question
Abstract only
91
Dzieciuchowicz, 2011 Incorrect study design (cross-sectional)
101
Gasparis, 2008 No relevant outcomes and also does not match review question
Abstract only
138
Kostas, 2010 No relevant outcomes and also does not match review question
142
Labropoulos, 2012 No relevant outcomes and also does not match review question
155
Mackenzie, 2003 No relevant outcomes and also does not match review question
162
McLafferty, 2009 Abstract. Authors contacted for more information but no reply received.
172
Moore, 2011 Incorrect study design (cross-sectional)
Abstract only
203
Pannier, 2012 No relevant outcomes and also does not match review question
Abstract only
175
Mota-Capitao, 1995 Incorrect study design - a cross-sectional study rather than a case control or

329

prospective cohort study
216
Rabe, 2010 Incorrect study design (commentary)
229
Robertson, 2011 No relevant outcomes and also does not match review question
Abstract only
271
Treiman, 2001 No relevant outcomes and also does not match review question
274
Uhl, 2005 Incorrect study design - a cross-sectional study rather than a case control or
prospective cohort study
2 J.2.2 Factors associated with better/worse response to treatment
3 Table 100: Studies excluded from the clinical review: Factors associated with better/worse
4 response to treatment
Ref ID Reason for exclusion
5
Ali, 2007 No relevant outcomes and does not match review question
6
Allegra, 2007 Incorrect study design - no multivariable analysis
10
Atkin, 2007 Incorrect study design - no multivariable analysis
12
Barrett, 2004 Incorrect study design - no multivariable analysis
38
Bush, 2012 Abstract only
39
Calcagno, 2009 Incorrect study design - no multivariable analysis
48
Carradice, 2011 No relevant outcomes and does not match review question
51
Chaar, 2011 Incorrect study design - retrospective
55
Chi, 2011 Abstract only
59
Ciostek, 2004 Incorrect study design - no multivariable analysis
61
Corbett, 2011 Incorrect study design - no multivariable analysis
Abstract only
74
Defty, 2008 Incorrect study design - no multivariable analysis
94
Einarsson, 1993 Intervention does not match protocol (liquid sclerotherapy)
108
Goode, 2009 No relevant outcomes and does not match review question
112
Hartmann, 2006 Incorrect study design - no multivariable analysis
115
Hingorani, 2009 Intervention does not match protocol
123
Jagtman, 2003 Intervention does not match protocol - liquid sclerotherapy
128
Kakkos, 2006 Incorrect study design - no multivariable analysis for the analysis frelevant
to the review question
133
Kim, 2006 Incorrect study design - no multivariable analysis
157
Magnusson, 2006 Incorrect study design – retrospective study
160
Marsh, 2010 Incorrect study design - no multivariable analysis
161
Marston, 2008 Incorrect study design - no multivariable analysis
164
Meissner, 2012 Abstract only
171
Miyazaki, 2005 Incorrect study design – retrospective study
177
Mouton, 2008 Population does not match protocol - inguinal varices
181
Nash, 1991 Incorrect study design - no multivariable analysis
183
Nelzen, 2010 Abstract only
192
Oguzkurt, 2010 Abstract only

330

196
Ozsvath, 2010 Abstract only
211
Pittaluga, 2009 Incorrect study design - no multivariable analysis
210
Pittaluga, 2012 No relevant outcomes and does not match review question
214
Puggioni, 2005 Incorrect study design - no multivariable analysis
215
Puggioni, 2009 Incorrect study design - no multivariable analysis
237
Sarvananthan, 2012 Incorrect study design - no multivariable analysis
246
Shepherd, 2009 Abstract only
245
Shepherd, 2010 Multivariable analysis, considering confounders such as sex, BMI or clinical
disease severity, but no report of the independent effects of each
confounder.
255
Stother, 1974 intervention does not match protocol (liquid sclerotherapy)
273
Tzilinis, 2005 Incorrect study design - no multivariable analysis
277
Van Neer, 2006 Incorrect study design - no multivariable analysis
278
Vandy, 2011 Abstract only
280
Ward, 2011 Abstract only
285
Wright, 2006 Incorrect study design - no multivariable analysis
289
Zamboni, 2010 Incorrect study design - no multivariable analysis
2 J.3 Chapter 7 – assessment for treatment

3 J.3.1 Diagnostic assessment of hand held Doppler
4 Table 101: Studies excluded from the clinical review: diagnostic assessment of hand held Doppler
Author/title Reason for exclusion
8
Antoch 2002 Does not address diagnostic accuracy
43
Campbell 2005 No diagnostic data presented
88
Dixon 1996 Does not address diagnostic accuracy
95
Engel 1991 Does not address diagnostic accuracy
194
Olivienca 1998 Does not address diagnostic accuracy
205
Phillips 1995 No HHD diagnostic data
209
Pierik 1997 No HHD diagnostic data
250
Singh 1997 No usable diagnostic data presented
288
Yamaki 2002 Does not address diagnostic accuracy
5 J.3.2 Duplex assessment prior to treatment
6 Table 102: Studies excluded from the clinical review

42
Campbell 1996 No relevant outcomes and does not match review question
49
Cavezzi 2000 Comparator does not match protocol - no comparator
50
Cavezzi 2007 No relevant outcomes and does not match review question
60
Coleridge-Smith 2007 No relevant outcomes and does not match review question

331

69
De Maeseneer 2011 No relevant outcomes and does not match review question
136
Krodowicz 2010 No relevant outcomes and does not match review question
145
Levi 1995 Population does not match protocol - population were patients
undergoing infrainguinal bypass procedures;
Comparator does not match protocol - no comparator
158
Makris 2006 No relevant outcomes and does not match review question
197
Pachler 1998 Comparator does not match protocol - no comparator
208
Pichot 2000 Comparator does not match protocol - no comparator
212
Pleass 1996 No relevant outcomes and does not match review question
234
Safar 2004 Comparator does not match protocol - no comparator
253
Somjen 1996 No relevant outcomes and does not match review question
42
Campbell 1996 No relevant outcomes and does not match review question
193
Oinonen 2007 No relevant outcomes and does not match review question - both
Duplex and hand held doppler were both used for pre-op marking, with
some patients only having been examined with HHD. Also, all patients
had a duplex/doppler assessment, the difference between groups being
that in one group the duplex/doppler findings were only communicated
to the surgeons in written form, whereas in the other group the
surgeon was allowed to do a pre-op marking, by utilising HHD and the
previous duplex/doppler findings.
1 J.4 Chapter 8 – conservative management

2 J.4.1 Compression vs. no treatment
3 Table 103: List of excluded studies

4
Ahfmr 1997 Incorrect study design - review
11
Bachoo 2009 Incorrect study design - review
37
Brown 1992 Comparator does not match protocol - other form of compression
52
Chant 1989 Comparator does not match protocol - other form of compression
54
Chant 1985 Comparator does not match protocol - other form of compression
81
Diehm 1996 Incorrect outcomes reported
102
Geraghty 1989 Probably the same study as Anderson 1990.
125
Jones 1980 Comparator does not match protocol - other form of compression
127
Kakkar 1982 Comparator does not match protocol - other form of compression
141
Labropoulos 1994 Incorrect study design – laboratory study
147
Lippmann 1994 Intervention does not match protocol - Unna’s boot
170
Michaels 2006 Comparator does not match protocol – liquid sclerotherapy).
174
Mosti 2011 Comparator does not match protocol- other form of compression
178
Murad 2011 Incorrect study design – systematic review
200
Palfreyman 2009 Incorrect study design – systematic review
260
Thaler 2001 No relevant outcomes and does not match review question
269
Tisi 2011 Incorrect study design – systematic review
4

332
1 J.4.2 Compression vs. interventional treatment

3
Abramowitz 1973 Intervention does not match protocol - liquid sclerotherapy only
13
Barwell 2004 Population does not match protocol - treatment of chronic ulceration
105
Gohel 2007 Population does not match protocol - treatment of chronic ulceration
104
Gohel 2005 Population does not match protocol - treatment of chronic ulceration
109
Guest 2003 Population does not match protocol - treatment of chronic ulceration
144
Leu 1993 Intervention does not match protocol – foam sclerotherapy and
compression applied concomitantly
200
Palfreyman 2009 Incorrect study design - systematic review.
240
Schul 2011 Population does not match protocol - CEAP1 only – not a true varicose
veins population.
248
Shingler 2011 Incorrect study design - systematic review.
3
4

333
1 J.5 Chapter 9 – interventional treatment

2 J.5.1 Stripping surgery vs. foam sclerotherapy

16
Belcaro2003 Intervention does not match protocol – avulsion
18
Belcaro2000 . Intervention does not match protocol – flush ligation and avulsion
20
Beresford1978 Comparator does not match protocol – liquid sclerotherapy
53
Chant1972 Comparator does not match protocol – liquid sclerotherapy
89
Doran1975 Comparator does not match protocol – liquid sclerotherapy
93
Eifell2006 . Incorrect study design - study protocol .
94
Einarsson1993 Comparator does not match protocol – liquid sclerotherapy
110
Haas2006 . Non English language publication
116
Hobbs1968 Comparator does not match protocol – liquid sclerotherapy
117
Hobbs1974 No relevant outcomes and does not match review question
124
Jakobsen1979 Comparator does not match protocol – liquid sclerotherapy
146
Liamis2005 . Abstract only
169
Michaels2006A Comparator does not match protocol – liquid sclerotherapy
171
Miyazaki2005 Incorrect study design - retrospective observational study and not an RCT.
178
Murad2011 No relevant outcomes and does not match review questions
94
Neglen1993 No relevant outcomes and does not match review questions
228
Rigby2004 . No relevant outcomes and does not match review questions
232
Rutgers1994 Comparator does not match protocol – liquid sclerotherapy
275
VanDenBos2009 . Incorrect study design - systematic review .
5 J.5.2 Stripping surgery vs. endothermal ablation

163
Anon2010 Incorrect study design - systematic review
14
Basel2012 Incorrect study design - probably non-randomised. Although stated in the
abstract that this paper was randomised, there is no mention of randomisation
in the paper itself. Instead, the methods section states that “the study was
planned as a retrospective study”.
33
Brar2010 Incorrect study design - systematic review
57
Christenson2010 Some patients with bilateral symptoms had each leg randomised to a different
group, making QoL and pain results rather meaningless (as perception will be
global not per leg).
66
Darwood2009 Incorrect study design - systematic review
71
De Medeiros2005 Intervention does not match protocol - laser group had high tie of SFJ – thus
“non-standard” laser
70
De Medeiros2006 Same study as de Medieros 2005, with identical outcomes
85
Disselhoff2008 intervention does not match the protocol - cryostripping
87

334

84
Disselhoff2009 Comparator does not match protocol - cryostripping instead of standard
stripping
86
130
Kalteis2008 Intervention does not match protocol - laser was combined with SFJ ligation –
thus “non standard” laser
140
Kundu2011 Incorrect study design - systematic review
149
Luebke2008 Incorrect study design - systematic review
184
Nesbitt2011 Incorrect study design - systematic review
257
Subramonia2010 Economic analysis and otherwise same study as Subramonia 2010B
259
Tellings2011 Incorrect study design - systematic review
261
Theivacumar2009 Incorrect study design - cohort study
279
Vuylsteke2006 Incorrect study design - not randomised
287
Xenos2009 Incorrect study design - systematic review
2 J.5.3 Foam sclerotherapy vs. endothermal ablation

135
King2009 Endovenous ablation and sclerotherapy applied concomitantly – not a
comparison.
137
Koroglu2011 Endovenous ablation and sclerotherapy applied concomitantly – not a
comparison.
150
Luebke2008 Incorrect study design - systematic review
4 J.5.4 Tributary treatment: avulsion vs. foam sclerotherapy

18
Belcaro 2000 Intervention does not match protocol - did not include avulsion surgery
16 Unclear if the foam sclerotherapy was a tributary treatment.
Belcaro 2003
15
Belcaro 2003B Identical report to the included Belcaro 2003 study.
35
Brethauer 2001 Comparator does not match protocol - liquid sclerotherapy
73 Comparator does not match protocol - liquid sclerotherapy
De Roos 2003
6

335
1 J.5.5 Truncal and tributary treatment vs. truncal treatment alone

17
Belcaro 1998 Non English speaking publication
18
Belcaro 2000 Intervention does not match protocol - liquid sclerotherapy
15
Belcaro 2003B Foam sclerotherapy was done up to 6 months after the surgery
132
Kim Comparator does not match protocol - included tributary treatments given
with endovenous ablation.
135
King 2009 Incorrect study design - no comparator
137
Koroglu Did not address the review question.
165
Mekako 2006 Incorrect study design - no comparator
168
Merchant 2005
No relevant outcomes and does not match review question
188
Nicolini 2005 Intervention does not match protocol - those receiving tributary treatments
included those receiving such treatments during the follow-up period (i.e. not
just those who had tributary treatments at the same time as the truncal
treatment)
233
Sadick 2007 Incorrect study design - no comparator
238
Schanzer 2010 Study comparator does not match protocol
264
Theivacumar 2006 Abstract only
265
Theivacumar 2007 Contained information that 40% of patients undergoing laser ablation to GSV
required delayed tributary treatment. However this paper did not address the
review question.
266
Theivacumar 2008 No relevant outcomes and does not match review question
267
Theivacumar 2008A This study had one group where sclerotherapy was used concomitantly with
EVLA, but this was not to treat tributaries (it was to treat below knee truncal
reflux).
261
Theivacumar 2009
263
Theivacumar 2009A
262
Theivacumar 2009B Contained information that 44% of patients undergoing laser ablation to GSV
required delayed tributary treatment. However this paper did not address the
review question.
283
Welch 2006
282
Weiss RA, Weiss MA.
3
4

336
1 J.6 Chapter 10 – compression after interventional treatment

23
Biswas 2007 Compared different durations of compression; this would have met the
inclusion criteria for part b) of the research question if part a) had shown a
reasonable level of efficacy for compression as an adjuvant therapy.
29
Bond 1999 Compared different types of compression; this would have met the inclusion
criteria for part b) of the research question if part a) had shown a reasonable
level of efficacy for compression as an adjuvant therapy.
72
de Roos 2008 Incorrect study design - no comparator
75
De Jode 1970
Intervention does not match protocol - liquid sclerotherapy used
83
Din 1992
73,100
Fraser 1985 Intervention does not match protocol - liquid sclerotherapy used
151
Lugli 2009 Compared different forms of compression; this would have met the inclusion
159
Mariani 2011 Compared different forms of compression; this would have met the inclusion
166
Melrose 1979 No relevant outcomes and does not match review question
173
Mosti 2009 Compared different levels of compression; this would have met the inclusion
190
O’Hare 2010 Compared different durations of compression; this would have met the
218
Raraty 1999 Compared different durations of compression; this would have met the
227
Rhodes 1972
231
Rodrigus 1991 Compared different durations of compression; this would have met the
248
Shingler 2011 Incorrect study design - systematic review
249
Shouler 1989 Compared different levels of compression; this would have met the inclusion
270
Travers No relevant outcomes and does not match review question
272
Tretbar 1970
281
Weiss 1999A

337
Excluded economic studies
1 Appendix K: Excluded economic studies

2 K.1 Chapter 8 – conservative management
3 K.1.1 Compression vs. interventional treatment
4 Table 111: Studies excluded from the economic review

96
Eskelinen et al. 2009 Economic analysis is based on a cohort study and it is unclear whether the
QALYs reported are correct. It is unclear whether the 15-dimension
quality-of-life instrument has been validated.
5 K.1 Chapter 9 – interventional treatment

6 K.1.1 Stripping surgery vs. foam sclerotherapy

20
Beresford et al 1978 Dated article
30
Bountouroglou et al 2006 This study did not report QALYs. More applicable evidence was available
for this comparison.
207
Piachaud & Weddell 1972 Dated article
206
Piachaud & Weddell 1972A Dated article
185
ZonMw 2005 Study results are not published. It is stated that a full report is available
from the authors. Attempts to make contact with the authors, however,
failed.
9 K.1.2 Stripping surgery vs. endothermal ablations

84
Disselhoff et al 2009 The study is an economic analysis carried out alongside a randomized
controlled comparing cryostripping with endovenous laser ablation.
92
Eidson et al 2011 This is a retrospective cohort study comparing the relevant treatments
over a 6 month period.
Medical Advisory Secretariat This is a costing and budget impact study to identify resource and cost
163
2010 differences between the two interventions compared.
Ontario Health Technology This is a costing and budget impact study to identify resource and cost
1
Advisory Committee differences between the two interventions compared.
219
Rasmussen et al 2007 This study was excluded as more recent results are reported in
221
Rasmussen et al. 2011 .
219
Rasmussen et al 2011 This study was based on the Danish healthcare system and does not
report QALYs. It has a lower applicability than other evidence for this
comparison.
224
Rautio et al 2002 This study was based on the Finish healthcare system and does not report

338
Excluded economic studies

QALYs. It has a lower applicability than other evidence for this
comparison.
252
Solis et al 2009 Actual cost estimates are not provided but rather symbols are used to
indicate that endovenous laser ablation is more expensive than stripping
surgery.
257
Subramonia and Lees 2010 This study does not report QALYs. It has a lower applicability than other
evidence for this comparison
279
Vuylsteke et al 2006 This study was based on the Belgian healthcare system and does not
report QALYs. It has a lower applicability than other evidence for this
comparison.
2 K.1.3 Foam sclerotherapy vs. endothermal ablation

221
Rasmussen et al 2011 This study was based on the Danish healthcare system and
does not report QALYs. It has a lower applicability than other
evidence for this comparison.

339
Cost-effectiveness analysis of interventional treatments and conservative care
1 Appendix L: Cost-effectiveness analysis of

2 interventional treatments and conservative care
3 L.1 Introduction
4 Interventional treatments for varicose veins (surgery, foam sclerotherapy and endothermal ablation
5 techniques) are likely to have significant resource implications, and as such it is important to identify
6 which of these treatments represents a cost-effective use of NHS resource. Two published UK
7 economic evaluations were identified in this area106,170Michaels and colleagues (2006) compared
8 surgery, liquid sclerotherapy and conservative care in various groups with differing stages of disease
9 and found surgery to be the most cost-effective option. However this analysis did not look at
10 endothermal techniques or foam sclerotherapy, and is therefore not complete for our purposes. The
11 second evaluation, Gohel and colleagues (2010), was subject to several limitations; in particular, the
12 costs were not thought to be representative of common practice as they were based on modified
13 reference costs, and the authors appear to assume that recurrence rates do not differ after different
14 modalities of treatment. The conclusions of the model must therefore be interpreted with caution,
15 and are of limited value in informing recommendations.
16 We are also aware of an on-going NHS Health Technology Assessment (HTA) project to investigate
17 the cost effectiveness of minimally invasive techniques.239 There is overlap between the HTA project
18 and the analysis presented here, however we are aware of a few key differences: in contrast to our
19 model, the aforementioned project does not include conservative care as a comparator, the clinical
20 outcomes included in the network meta-analysis (NMA) are different, and as such the model is based
21 on different clinical data. The HTA project is still being revised, therefore no further comment can be
22 made here. Overall, the GDG did not deem the existing literature to be sufficient on which to base
23 recommendations. Interventional treatments were therefore identified as a priority for original
24 economic analysis.
25 Initially it was planned that analyses would also look at the cost-effectiveness of these treatments at
26 different stages of the disease, thereby addressing the question of the optimal timing of
27 intervention. However, a lack of relevant data meant this was not possible. This analysis therefore
28 focuses on the cost effectiveness of the various interventional treatments for varicose veins, in
29 comparison to non-invasive conservative care, in the general primary varicose veins population.
30 Analysis of patients with bilateral disease was carried out separately as a cost-comparison, with the
31 results and their implications discussed thoroughly by the GDG.
32 L.2 Methods
33 L.2.1 Model overview
34 A cost-utility analysis was undertaken where costs were considered from a UK NHS and personal
35 social services perspective and health outcomes expressed as quality adjusted life years (QALYs).
36 Costs and QALYs were both discounted at 3.5% per annum, in accordance with the NICE reference
37 case182.
38 L.2.1.1 Comparators
39 Four treatments were considered in the base case:

340
1 • Surgery (stripping and ligation) – with or without tributary treatment, carried out as a day case
2 procedure under general anaesthetic
3 • Endothermal techniques (RFA & EVLA) with concurrent phlebectomy – carried out as an
4 outpatient procedure under local anaesthetic
5 • Foam sclerotherapy – with or without tributary treatment, carried out as an outpatient procedure
6 under local anaesthetic
7 • Conservative care (compression therapy)
8
9 Endothermal techniques without concurrent phlebectomy were evaluated as a sensitivity analysis.
10 L.2.1.2 Population
11 Adults with primary unilateral great saphenous vein (GSV) incompetence, who are potentially
12 suitable for treatment by any of the four treatment options.
13 In some cases, particular treatments may not be suited to an individual patient. Decision models are
14 designed to identify the optimal choice between two or more alternative strategies; the choice
15 between the comparators only applies to people for whom all of these are a possibility.
16 Sensitivity analyses included unilateral patients receiving concurrent treatment of the small
17 saphenous vein (SSV), and a cost comparison to inform GDG discussion around treatment of patients
18 with bilateral varicose veins.
19 L.2.1.3 Time horizon
20 The time horizon of the model was five years in the base case. This was chosen as the appropriate
21 horizon as there is no differential mortality effect between treatment options, and no reliable
22 evidence was found to document differences in costs and health related quality of life past this time
23 horizon. Extrapolation of follow-up data (data is limited to a 3 year follow-up) past the 5 year time
24 horizon would have been subject to a great deal of uncertainty and was not deemed to be
25 appropriate in this instance.
26 Sensitivity analyses included evaluation over a 3 year time horizon, in line with the maximum follow-
27 up time of the clinical data.
28 L.2.2 Approach to modelling

29 Interventional treatments for varicose veins are used to occlude, obliterate or strip varicose veins,
30 thereby reducing patient symptoms and improving quality of life. When these outcomes are not
31 achieved, top-up treatment can be given to supplement the initial treatment. For the purpose of the
32 model, this combination of initial treatment and top-up treatment was considered to be one
33 treatment episode. All patients in the model have an initial treatment episode (either outpatient or
34 day case depending on the treatment option), with different treatments leading to different
35 proportions of individuals requiring top-up treatment, resulting in a difference in costs and QALYs
36 associated with the initial treatment episode.
37 Patients in the model experience an increase in quality of life (QoL) once the initial treatment
38 episode is complete. The difference in QALYs was driven by the length of time this increase in QoL
39 was sustained for, before a patient experienced recurrent varicose veins. The probability of having
40 recurrent varicose veins differed by treatment and for the purpose of the model was taken from a
41 network meta-analysis described in section L.2.3.2.2 below. The NMA was based on clinical
42 recurrence data, which was used to capture the development of symptoms of varicose veins in a
43 treated limb. Clinical recurrence was chosen over other possible definitions of recurrence because

341
1 symptoms (as opposed to reflux, recanalisation, or any other definition) have a direct impact on QoL.
2 Patients could undergo a second treatment episode in the model, to alleviate symptoms of recurrent
3 varicose veins and improve QoL again. Further information and technical details are given in the
4 subsequent sections.
5 L.2.2.1 Key definitions
6 A treatment episode consists of a treatment for every patient, and a top-up treatment for the
7 proportion of individuals who require it. There is potential for two treatment episodes in the model;
8 an initial treatment episode which all patients in the model receive, and a second treatment
9 episode which is given to a proportion of individuals following clinical recurrence. The second
10 treatment episode is distinct from top-up treatment, which is considered to be part of a treatment
11 episode.
12 Top-up treatment is given as part of a treatment episode (within 2 months of the initial treatment) if
13 treatment is not deemed to be complete (i.e. if the vein undergoing treatment has not been
14 occluded or obliterated, or if additional treatment of residual varicosities is needed). Top-up
15 treatment was assumed to always be foam (see Table 115). In some cases the need for top-up
16 treatment could be identified by a follow-up appointment if one is given, or the top-up treatment
17 could have been planned before the initial treatment; in other cases, the patient may present with a
18 need for top-up treatment. The inclusion of top-up treatment in the model is not intended to imply a
19 recommendation of routine follow-up appointments. The concept of top-up treatment is adapted
20 from the aforementioned HTA project,239 in which it is used to refer to residual varicose veins, and
21 does not include unsuccessful occlusion.
22 Clinical recurrence is defined as development of symptoms of varicose veins in a treated limb. For
23 the purpose of the network meta-analysis, papers which report clinical recurrence as an outcome
24 were taken at face value.
25 L.2.2.2 Model structure
26 A Markov model was constructed to calculate costs and QALYs for each comparator; the key health
27 states and transitions can be seen in Figure 159. The simplified diagram does not show death, but
28 patients could die of all-cause mortality at any point during the model’s five year time horizon.
29 Patients enter the model through the ‘First treatment episode’ state. Following completion of the
30 treatment episode, patients move to a state of ‘treatment episode complete’, where they do not
31 require any further treatment. They remain in this state until they experience clinical recurrence, at
32 which point they transition to the state ‘Physical symptoms with recurrent VVs (1)’. Patients cannot
33 experience clinical recurrence in the first three cycles post treatment, to allow time for all top-up
34 treatments to take place.
35 Only a proportion of patients with clinical recurrence go on to have further interventional treatment,
36 whilst the rest receive conservative care. For those who do receive further interventional treatment,
37 a delay of 6 months is assumed between the onset of clinical recurrence and the second treatment
38 episode. This delay is based on clinical opinion and captured in the model through a series of tunnel
39 states (these states are omitted from Figure 159 for simplicity). Following the second treatment
40 episode, a patient can experience clinical recurrence again, but will not receive further treatment;
41 instead they remain in the state of ‘physical symptoms with recurrence VVs (2)’ and receive
42 conservative care. Conservative care received at this point is assumed not have an impact on QoL
43 Conservative care was modelled separately to the other three interventions, as the outcomes of
44 completed treatment and clinical recurrence are not clinically meaningful when considering this
45 management technique. Instead, the difference in quality of life between patients undergoing
46 surgery and conservative care (as reported in Michaels2006170) was used to calculate the difference

342
1 in QALYs over time between these two treatments. This information was then used to calculate the
2 QALYs expected from conservative care, relative to the QALYs computed by the model for surgery.
3 Costs were calculated by applying an annual cost to all those individuals in the model and receiving
4 conservative care.
6 Figure 159: Model diagram
7
8 Schematic diagram of the Markov model designed to compare the cost-effectiveness of treatments for varicose
9 veins. The Markov modelling approach involves a transition between different health states over time. The model
10 is divided into monthly cycles. At the end of each cycle a transition to another health state is possible, unless
11 people enter into an ‘absorbing state’ from which they cannot transition. In this model, the absorbing state is
12 ‘Physical symptoms with recurrent VVs (2)’.
13 The model was built with a one month cycle length as this was deemed to be the minimum clinically
14 meaningful time interval to detect differences between interventions. All the probabilities, costs and
15 health utilities were converted to reflect the one-month cycle length.
16 L.2.2.3 Key assumptions
17 The model employed the following key assumptions:
18 Table 115: Key assumptions

Assumption Comment
Rates of top-up treatment are the same in the initial The GDG deemed this to be a reasonable
and second treatment episode (ie after retreatment) assumption
Top-up treatment is always foam sclerotherapy As the modality of top-up treatment does not affect
the rate of recurrence (see assumption below), this
will only effect the cost of top-up treatment. The
GDG deemed this to be a reasonable simplifying
assumption.

343
Assumption Comment
Patients who have had top-up treatment have the The GDG deemed this to be a reasonable simplifying
same probability of recurrence as those who haven’t assumption
had top-up
Constant hazard of recurrence This was deemed to be a reasonable simplifying
assumption as the time horizon of the model is
relatively short
There is a 6 month delay between the onset of This is included to reflect the time between the
clinical recurrence and the second treatment onset of symptoms and subsequent interventional
episode treatment.
A patient can only receive two treatment episodes in This is a simplifying assumption for the model but is
total expected to be a fair reflection of routine clinical
practice
Proportions of patients having each modality of The method of retreatment is more likely to be
second treatment is independent of the modality of based on individual patient characteristics and the
their initial treatment nature of the recurrence, rather than the modality of
initial treatment. As the model cannot capture these
factors for individual patients, the GDG deemed this
to be a reasonable assumption.
1 L.2.2.4 Uncertainty
2 The model was built probabilistically to take account of the uncertainty surrounding each input
3 parameter. In order to characterise uncertainty, a probability distribution was defined for each
4 parameter based on error estimates from the data sources (e.g. standard errors or confidence
5 intervals). The way in which distributions are defined reflects the nature of the data (see Table 116).
6 When the model was run, a value for each input was randomly selected from its respective
7 distribution. The model was run repeatedly (10, 000 times) to obtain mean cost and QALY values.
8 Various sensitivity analyses were also undertaken to test the robustness of model assumptions and
9 data sources. In these analyses, one or more inputs were changed and the analysis was rerun in
10 order to evaluate the impact of these changes on the results of the model.
11 Table 116: Distributions used in probabilistic cost-utility analysis

Type of
Parameter distribution Properties of distribution
Cost Gamma Bounded at 0, positively skewed. Derived from mean
and standard error
Pre-treatment utility Beta Bounded on 0 – 1 interval. Derived from mean and
sample size
Utility improvements and Lognormal Bounded at 0. Derived from log of mean utility change
decrements and standard error of log of utility change
Utility difference between Normal Derived from mean and variance
conservative care and surgery
Baseline risk and relative effects Distribution estimated by sampling from network meta-analysis output
12 L.2.3 Model Inputs
13 L.2.3.1 Summary table of model inputs
14 Model inputs were based on clinical evidence identified in the systematic review undertaken for the
15 guideline, supplemented by additional data sources as required. All inputs were checked for face

344
1 validity by the clinical members of the GDG. A summary of the model inputs used in the base-case
2 analysis is provided in Table 117 Table 118 below. More details on sources, calculations and rationale
3 for selection can be found in subsequent sections.
4 Table 117: Summary of base-case model inputs and cohort settings

Input Source
Comparators Surgery, foam sclerotherapy, endothermal GDG consensus
with phlebectomies, conservative care
Population Adults with primary unilateral GSV GDG consensus
incompetence
Initial cohort settings Age: 50 Weighted average across relevant
1
Female: 65% RCTs
182
Perspective NHS and PSS NICE reference case
Time horizon 5 years GDG consensus
182
Discount rate Costs: 3.5% NICE reference case
QALYs: 3.5%
5 GSV = great saphenous vein
1
6 the RCTs included in the network meta-analysis for clinical recurrence
7 Initial cohort settings
8 A starting age of 50 was used in the model to represent the average age of people undergoing
9 treatment for varicose veins, and the cohort was assumed to be 65% female, based on the
10 characteristics of patients in the included RCTs. These cohort characteristics were validated against
11 HES data121 which confirms that the average age of patients undergoing day case treatment for
12 varicose veins is approximately 50, and that roughly two thirds of these patients are female.
13 Table 118: Overview of parameters and parameter distributions used in the model
Point Probability Distribution
Parameter description estimate distribution parameters Source
Utility weights
119
Primary varicose veins 0.764 Beta α = 37600, β = 12800 PROMs
119
Change in utility (from +0.091 Lognormal μ = -2.397, σ = 0.0007 PROMs
baseline) post treatment
21
Change in utility (from -0.093 Lognormal μ = -2.206, σ = 0.0128 Beresford 2003
baseline) due to recurrent
varicose veins
170
Conservative care (relative -0.101 Normal μ = 0.0004, σ = 0.0198 Michaels 2006
to surgery at 1 year)
Transition probabilities
Probability of requiring top-up treatment (within 2 months post treatment)
Surgery 5% Deterministic SA only GDG estimate
Endothermal 5% Deterministic SA only GDG estimate
Foam Sclerotherapy 20% Deterministic SA only GDG estimate
Conservative care NA
Probability of recurrence (per month)
Surgery 0.008331 Point estimate and uncertainty from NMA
Endothermal 0.005833 Point estimate and uncertainty from NMA
Foam Sclerotherapy 0.009141 Point estimate and uncertainty from NMA

345
Point Probability Distribution

Parameter description estimate distribution parameters Source
Conservative care NA
Cost (£)
Surgery £908 Gamma See Table 126 See Table 126
Endothermal £624 Gamma See Table 128 See Table 128
Foam Sclerotherapy £315 Gamma See Table 129 See Table 129
a
Conservative care £234 Deterministic SA only
Additional cost associated £417 Gamma See Table 131 See Table 131
with retreatment
1 SA = Sensitivity analysis; NMA=network meta-analysis
a
2 this is an annual cost (first year incurs and additional £15)
3 L.2.3.2 Baseline event rates and relative treatment effects
4 L.2.3.2.1 Top-up treatment rates
5 Limited data on treatment failure was available from the randomised trials, often based on different
6 definitions of failure and very short follow-up of just a few days. In addition, treatment failure,
7 however defined, is not the only reason that top-up treatment may be undertaken. For example,
8 further treatment could be necessary to eradicate residual varicosities which were not treated
9 initially (this may or may not have been planned at the time of the initial treatment). The data on
10 treatment failure from the trials was therefore not considered to be relevant to the need for top-up
11 treatment as defined in our model. For this reason, the proportions of patients requiring top-up after
12 each treatment are based on GDG estimate (see Table 118).
13 L.2.3.2.2 Clinical recurrence
14 The results of conventional meta-analyses of direct evidence alone make it difficult to determine
15 which intervention is the most effective treatment. The challenge of interpretation has arisen for two
16 reasons:
17 • In isolation, each pair-wise comparison does not fully inform the choice between all the possible
18 treatments, and having a series of discrete pair wise comparisons can be disjointed and difficult to
19 interpret
20 • There are overlapping comparisons that could potentially give inconsistent estimates of effect.
21 This is particularly problematic for probabilistic analysis. To overcome these problems, a Bayesian
22 network meta-analysis (NMA)40 was conducted in WinBUGS.
23 Conventional meta-analysis assumes that, for a fixed-effect analysis, the relative effect of one
24 treatment compared to another is the same across an entire set of trials. In a random-effects model,
25 it is assumed that the relative effects are different in each trial but that they are from a single
26 common distribution and that this distribution is common across all sets of trials.
27 Network meta-analysis requires an additional assumption over conventional meta-analysis. The

28 additional assumption is that intervention A has the same relative effect across all trials of
29 intervention A compared to intervention B as it does across trials of intervention A versus
30 intervention C, and so on. Thus, in a random-effects network meta-analysis, the assumption is that
31 intervention A has the same effect distribution across all trials of A versus B, A versus C and so on.
32 The aim of the NMA was to calculate treatment-specific probabilities of clinical recurrence following
33 each of the different treatments. Clinical recurrence was chosen over other possible definitions of
34 recurrence because symptoms (as opposed to reflux, recanalisation, or any other definition) are most

346
1 likely to have an impact on QoL. The GDG did not think it was appropriate to combine different
2 measures of recurrence into one measure of effect. The definition of clinical recurrence as used in
3 this analysis was given in section L.2.2.1.
4 Statistical analysis
5 When modelling an outcome such as clinical recurrence, it is important to consider the different
6 follow-up times of the various trials, as longer follow-up is likely to result in more reported
7 recurrences. To account for this, an underlying Poisson process with a constant event rate was
8 assumed for each trial arm, and a complementary log-log (cloglog) link function used to model the
9 event rate. The following logic was used to calculate hazards and hazard ratios:
10 Let and denote the baseline hazard (from the surgery arms) and treatment-specific hazard
11 ratio for clinical recurrence; let represent the cloglog of the probability of recurrence, , and let
12
represent the duration of follow-up. Then:
= (
) + () + ()
13 And:
= 1 − exp {−exp }
14 Surgery was chosen as the baseline comparator as it featured in the most trials. The baseline hazard
15 was estimated on the clog-log scale through a meta-analysis of the surgery arms of the included
16 trials. The resulting predictive distribution was inputted to the NMA for adjustment by the treatment
17 specific hazard ratios to calculate the probability of clinical recurrence for each treatment. The codes
18 for both the baseline and relative effects models were adapted from that provided on the NICE
19 decision support unit website, and run in WinBUGS 14.
20 The baseline and relative effects models were run for 50,000 iterations with burn in periods of
21 50,000. Vague uninformative priors were combined with the data-driven likelihood functions to
22 produce posterior probability estimates. Convergence was assessed by examining the history and
23 kernel density plots.
24 Fixed and random effects NMAs were run, and goodness of fit estimated by calculating the total
25 residual deviance and deviance information criteria (DIC) for each of the models. A total residual
26 deviance close to the number of unconstrained data points (the number of trial arms in the analysis)
27 indicated a model explaining the data at a satisfactory level. The DIC provides a measure of goodness
28 of fit which penalises model complexity,79 which is useful for comparing models. The choice of a fixed
29 or random effects model can therefore be made by comparing their goodness-of-fit to the data.
30 Network and Data

31 A total of eight studies included in the clinical reviews of the relevant treatments included
32 clinical recurrence as an outcome. The trials included a variety of patients at differing
33 levels of severity of varicose veins, further information on the trials can be found in
34 chapters X and X of the full guideline. Surgery featured in all eight of the trials,
35 endothermal treatment featured in seven, and foam sclerotherapy in two. One trial
36 included all three comparators. The network of trials compared in the NMA is shown
37 in Figure 160 and the included data in

347
1 Table 119. In
2 Figure 160 the number of trials included for each pair-wise comparison is noted in parentheses.
3 Note that the comparison between sclerotherapy and endothermal treatment includes only one trial.
4 This single included study is a three arm trial which includes all of our comparators. Three arm trials
5 are internally consistent, and as such there is no potential for inconsistency within our network, only
6 for between-trial heterogeneity. This is discussed further by Dias and colleagues in technical support
7 document 4,80 in which the authors explain that ‘loops of evidence that are potentially inconsistent
8 can only arise from structures in which there are three distinct trials or sets of trials’.
9 Figure 160: Network of trials compared in the network meta-analysis
10
11 Surgery
12 (7)
13 (2)
14
15
16 (1)
Foam sclerotherapy Endothermal treatment
17
18

348
1 Table 119: Clinical recurrence trial data for network meta-analysis

Total number of Treatments
Clinical recurrence patients compared
Follow up
time Arm Arm Arm Arm Arm Arm Arm Arm Arm
Study name (months) 1 2 3 1 2 3 1 2 3
244
Shadid 2012 24 16 24 - 177 213 - S FS -
Rasmussen 12 16 17 23 108 123 245 S FS E
221
2011
Carradice 12 23 5 - 113 124 - S E -
46
2011
113
El Kaffas 2011 24 9 12 - 90 88 - S E -
204
Perala 2010 36 2 5 - 13 15 - S E -
213
Pronk 2010 12 3 3 - 56 49 - S E -
Rasmussen 24 25 18 - 68 69 - S E -
220
2010
222
Rass 2011 24 33 28 - 143 173 - S E -
2 Abbreviations: S = surgery; E = endothermal treatment; FS = foam sclerotherapy
3 Network meta-analysis results
4 The total residual deviance was 25.3 for the fixed effects model and 18.6 for the random effects
5 model which, when compared to 17 unconstrained data points, shows that the random effects
6 model fitted the data reasonably well. DIC statistics of 105.5 and 103.4 were calculated for the fixed
7 effects and random effects models respectively which, although the difference is small, suggests that
8 the random effects model is the preferred option. Results are therefore presented for the random
9 effects model only.
10 The final treatment-specific probability estimates and their associated confidence intervals can be
11 seen in Table 7.
12 Table 120: Network meta-analysis results – probability of clinical recurrence

Clinical recurrence (probability per month)
Treatment Mean Standard deviation Median Credible interval
Surgery 0.008818 0.00306 0.008331 0.004284 - 0.0161
Endothermal 0.006532 0.003448 0.005833 0.002424 – 0.01472
treatment
Foam 0.01115 0.009929 0.009141 0.002795 – 0.03093
sclerotherapy
13 As shown in Table 121, endothermal treatment was associated with the lowest probability of
14 recurrence per month. These estimates were used to parameterise treatment effects in the decision
15 model; deterministic point estimates were based on median values, with PSA values sampled from
16 the WinBUGs CODA output.
17 A posterior estimate of heterogeneity - the between trial standard deviation - was found to be 0.58.
18 An estimate of this magnitude indicates a large amount of variation in treatment effects calculated
19 from different trials.
20 L.2.3.2.3 Retreatment
21 Not all patients are retreated after experiencing clinical recurrence; for some patients this is because
22 they do not wish undergo further treatment, whereas for others it is because they are not deemed

349
1 suitable for further treatment. The GDG estimated that 75% of patients would receive further
2 interventional treatment, and it was assumed that the remaining 25% would receive conservative
3 care. This estimate was subject to wide ranging deterministic sensitivity analysis.
4 For those individuals who do undergo a second treatment episode, the mode of treatment is likely to
5 depend on the nature of their recurrence, alongside further patient characteristics. The GDG
6 estimated that the following proportions of patients would have each type of retreatment (Table
7 121).
8 Table 121: Method of retreatment

Second treatment % patients receiving each method of retreatment
Surgery 12%
Foam sclerotherapy 42%
Endothermal techniques 46%
9 These proportions represent an average over the 5 year time horizon, and were the same
10 irrespective of the modality of the initial treatment. There is substantial uncertainty surrounding
11 these estimates, however due to the nature of the model they are unlikely to drive the results.
12 Nevertheless, these proportions were subject to extensive deterministic sensitivity analysis (see
13 section 0).
14 L.2.3.2.4 Adverse events
15 Evidence on adverse events due to treatment identified by the clinical review was weak; different
16 trials report different outcomes, and measure them in different ways. For example, pain is measured
17 by VCSS at 1, 2 and 6 months in Figueiredo 2009,97, as a dichotomous outcome at one year in Pronk
18 2011,213 and by SF-36 in Rasmussen 2011.221 In addition, the GDG members felt that the adverse
19 event profiles of the different treatments were similar to the extent that their inclusion would not
20 benefit the model; therefore adverse events were not included in the analysis.
21 Whilst factors such as time to return from work, and time to return to usual activities may differ
22 between treatments, these do not fall within the model’s perspective of the NHS and PSS, and are
23 therefore outside the remit of this analysis.
24 L.2.3.2.5 Mortality
25 The treatments considered in the analysis are not assumed to have any differential effect on
26 mortality, yet patients can die at any point in the model. Age-specific all-cause mortality, weighted
27 for the gender split of the cohort population, was based on the most recent available life tables for
28 England and Wales (2008-20010).191
29 L.2.3.3 Utilities
30 In cost-utility analyses, measures of health benefit are valued in terms of quality adjusted life years
31 (QALYs). The QALY is a measure of a person's length of life weighted by a valuation of their health
32 related quality of life (QoL) over that period. The weight used is called a utility value, which is a
33 measurement of the preference for a particular health state, with a score ranging from 0 (death) to 1
34 (perfect health). Questionnaires such as the SF-36 and SF-12 provide generic methods of describing
35 QoL, while the EQ-5D, HUI, and SF-6D also include preference-based valuations of each health state,
36 allowing calculation of utility scores.
37 The preferred method for determining utilities for NICE economic evaluations is the EuroQoL (EQ-
38 5D) questionnaire182. The EQ-5D comprises five dimensions of health: mobility, ability to self-care,

350
1 ability to undertake usual activities, pain and discomfort, and anxiety and depression. For the NICE
2 reference case, preferences from the general public should be used. In keeping with this preference,
3 EQ-5D data was collected from the RCTs included in the clinical review. Only four studies provided
4 EQ-5D data, all of which are shown in Table 122. Studies which reported SF-36 data or disease
5 specific quality of life measures (such as the AVVQ or CIVIQ2) without EQ-5D are not included here.
6 Table 122: EQ-5D data from clinical trials

Relevant Utility values
Study comparators Baseline 3 months 6 months 12 months 24 months
461
Carradice 2009 EVLA + 0.81 (0.79- 1.0 NR 1.0 (1.0 – NR
2 2
phlebectomy 1.0) 1.0)
EVLA without 0.83 (0.75 0.82 NR 1.0 (0.89 – NR
2 2
phlebectomy – 1.0) 1.0)
48
Carradice 2011 Surgery 0.84 (0.8 – NR NR 1.0 (0.84 – NR
2 2
1.0) 1.0)
EVLA 0.85 (0.8 – NR NR 1.0 (0.87 – NR
2 2
1.0) 1.0)
Michaels Surgery 0.76 (0.19) NR 0.89 (0.13) 0.87 (0.14) 0.84 (0.21)
170
2006 (Group 3 Conservative care 0.77 (0.18) NR 0.80 (0.17) 0.78 (0.18) 0.85 (0.17)
only: severe
varicose veins)
244
Shadid 2012 Surgery Change from baseline at 2 years: +0.064 (NR)
Foam Change from baseline at 2 years: +0.061 (NR)
sclerotherapy
7 Abbreviations: NR = not reported
8 Values are mean (SD) EQ-5D scores unless otherwise stated
1
9 Mean utility values estimated from low resolution graph. Graph also reports data at 1 week and 6 week follow-up
2
10 median (interquartile range)
11 EQ-5D is not consistently reported in the trials. It is clear from Table 122 that this outcome is
12 reported at different follow-up times for the different comparators, thus the evidence does not lend
13 itself to an accurate comparison of the quality of life after each treatment individually. A search of
14 the economic and quality of life literature was therefore carried out to supplement the EQ-5D data
15 found in the trials. The search identified two economic analyses which included EQ-5D data106,170:
16 Gohel and colleagues employed the baseline and post treatment EQ-5D scores from the surgery arm
17 in Michaels, and the modelling section of Michaels used a combination of SF-6D and EQ-5D from the
18 same trial. Two additional economic evaluations84,223 were found which used utility data calculated
19 from the SF-6D. None of these economic analyses were considered beneficial in informing utility
20 inputs for our model.
21 The search also identified two further randomised trials which included EQ-5D data.90,189 Neither of
22 these studies were included in the clinical review for this guideline because the treatments compared
23 in these trials were not relevant to the clinical questions included in this guideline. These studies
24 were therefore not considered to be useful in informing inputs for the model.
25 An additional source of utility data is the Patient Reported Outcome Measures (PROMs), collated by
26 the Department of Health (DH). Since 2009, the DH has required providers of varicose veins surgeries
27 in England to collect and report PROMs. In practice, this means that all providers of NHS-funded
28 varicose vein surgeries are expected to invite patients to complete a pre-operative questionnaire.
29 Post-operative questionnaires are then sent to patients at least 3 months following their operation.
30 The questionnaires completed by the patient, record self-reported health status assessed through a
31 mixture of generic (EQ-5D and EQ-VAS) and condition-specific (AVVQ) questions. Where EQ-5D data

351
1 is collected, this can be used to calculate the mean pre- and post-treatment utility scores of
2 individuals receiving these treatments across England.
3 As of October 2012, finalised data are available for April 2010- March 2011. 8,624 records are
4 available from varicose veins patients with valid EQ-5D responses in both pre- and post-operative
5 questionnaires.120 The mean utility score pre- and post-treatment, is available on the HES website,
6 however this data does not specify results by varicose veins procedure. In theory, a dataset can be
7 purchased from the Department of Health which would allow the data to be analysed by varicose
8 veins procedure. However, given the likely population biases and computational time associated with
9 analysis of such a large, incomplete data set, it was not thought that the benefits of purchasing this
10 data set would justify the cost.
11 The PROMs data available from the HES website119 is documented in Table 123.
12 Table 123: PROMs data

Mean EQ-5D SD Number of completed questionnaires
Baseline 0.746 0.234 14533
1
Health gain post treatment +0.096 0.256 8624
1
13 all valid post-operative questionnaires, for which there is a valid pre-operative questionnaire
14 Neither the data from the clinical review, nor the PROMs data provide reliable differential figures on
15 the increase in utility following the different types of treatment. Therefore in the model patients
16 receive the same increase in utility after treatment, regardless of treatment type. The PROMs data
17 was used in preference to the clinical trial data in the model, as it reflects the mean change in utility
18 for individuals undergoing treatment for varicose veins in routine clinical practice.
19 The baseline value was used in the model to represent the utility of a patient with primary varicose
20 veins, i.e. when a patient first receives treatment. As PROMs data is measured at a minimum of 3
21 months after treatment, the health gain was applied 3 months after completed treatment (either
22 initial or secondary). The increase in utility over the 3 months immediately after treatment was
23 assumed to be linear, and was applied in the model through a series of tunnel states until the 3
24 month post utility value was achieved. For the probabilistic analysis, the baseline value was modelled
25 with a Beta distribution, and the health gain was modelled with a Lognormal distribution, as specified
26 in Table 118.
27 Utility decrement associated with recurrent varicose veins
28 We conducted a search to investigate whether recurrent varicose veins were associated with a
29 different level of QoL to primary varicose veins. Two studies21,198 were identified in this area,
30 although neither reported utility values. One study mentioned SF36 data but was only available in
31 abstract form,198 and the other reported SF-36 data.21 Both of these papers were co-authored by
32 GDG members, who we approached for further information, yet unfortunately no further data was
33 available.
34 In 2008, Ara and Brazier published a method of predicting mean EQ-5D preference based index score
35 using published mean cohort statistics from the eight dimensions of the SF-36 health profile.9
36 Therefore, in the absence of any utility data, we mapped the SF-36 data from Beresford 200321 to the
37 EQ-5D. In order to use the mapping algorithms, values for each of the eight dimensions of the
38 questionnaire are required. These values were only reported in graphical format, and were therefore
39 estimated using Grab it!, a programme which can be used to digitise graphs. The estimation was
40 made 3 times, and a mean value taken. The resulting values for each of the SF-36 domains are
41 documented in Table 124.
42 Ara and Brazier present several different equations to predict EQ-5D from SF-36, the choice of which
43 depends on the outcome to be mapped. Ara and Brazier state 'when comparing incremental

352
1 differences between study arms or changes over time, Equation 4 is the preferred choice'; the
2 outcome of interest here was the difference between the utility of people with primary and
3 recurrent varicose veins, thus Equation 4 was chosen. No measure of uncertainty was provided in the
4 graph, so the mapping algorithm was applied deterministically. The results of the mapping exercise,
5 including the difference in utility between individuals with primary and recurrent varicose veins, are
6 provided in Table 124. In the model, the utility of individuals with recurrent varicose veins was
7 calculated by subtracting the difference from the primary varicose veins utility weight, and was
8 modelled probabilistically using a Lognormal distribution (Table 118).
9 Table 124: SF-36 and EQ-5D data for primary and recurrent varicose veins
PF SF RP RE MH VT BP GH EQ-5D Difference
Primary 82.1 87.1 78.8 87.4 77.5 64.0 71.7 74.8 0.907
Recurrent 70.7 75.1 63.8 75.2 65.8 53.7 62.2 64.5 0.814 0.093
10 Abbreviations: PF = physical functioning; SF = social functioning; RP = role – physical; RE = role – emotional; MH = mental
11 health; VT = vitality; BP = bodily pain; GH = general health
12 Utility for conservative care
13 As mentioned previously, conservative care was modelled separately to the main analysis. The
14 difference in utility between patients undergoing surgery and conservative care was used to calculate
15 the difference in QALYs over time between these two treatments. The difference in utility between
16 these two treatments was taken from Michaels and colleagues170 (see Table 122), as this was the
17 only paper found to report such data. Utility values are given at baseline, 1 month, 6 months, 12
18 months and 24 months post treatment; however by the 24 month follow-up, a large proportion of
19 individuals had been lost to follow-up, and an unexpected large jump in utility is reported. This data
20 was included in the base case analysis, and sensitivity analyses investigated the impact of omitting
21 this 24 month data and extrapolating from the 12 month follow-up. The 1 month data was not
22 included, as the GDG did not consider data collected within 3 months post treatment to be reliable,
23 and because short term follow-up utility data was not included for the other treatment modalities.
24 The difference in utility was adjusted for the difference at baseline, and changes in utility over time
25 (for example between baseline and 6 months) were assumed to be gradual and linear. For the
26 probabilistic analysis the difference between utility following conservative care and surgery was
27 modelled using a Normal distribution to allow positive and negative differences.
28 L.2.3.4 Resource use and costs
29 Costs were associated with the following health states: initial treatment episode, physical symptoms
30 with recurrent VVs (1), second treatment episode and physical symptoms with recurrent VVs (2). The
31 cost of the initial and second treatment episodes included the cost of a main treatment, as well as
32 top-up treatment where applicable. The costs borne in the recurrent VVs states when no
33 interventional treatment was being delivered were due to the on-going costs of conservative care
34 given to people in those states.
35 Cost of interventional treatments
36 NHS reference costs do not distinguish between the different varicose vein treatments, but rather an
37 overall cost is given for primary unilateral varicose veins procedures (differs whether the procedure
38 is conducted as a day case, outpatient procedure etc.). Consequently NHS references costs could not
39 be used to capture the different costs of the treatments.
40 A review of existing economic literature was conducted in order to identify the costs of the various
41 treatments. Five UK studies30,106,143,170,257 were identified (See Table 125).
42

353
1 Table 125: UK relevant cost estimates from existing economic literature

Study Surgery Endothermal FS CC Costing technique
Bountouroglou £1,120.64 NA £672.97 NA Costs collected alongside
30
2006 RCT
106
Gohel 2010 £980 EVLA £1,524 £202 £0 Based on NHS reference
RFA £776 costs, adapted with
additional information from
manufacturers and list
prices.
143
Lattimer 2012 NA £724.72 £126.39 NA Costs collected alongside
1
(£676.74 - (NR) RCT
1
£773.85)
Michaels £642.66 NA NA £267.52 Costs collected alongside
170 2 2,3
2006 and (236.39) (350.91) RCT
223
Ratcliffe 2006
Subramonia £559.13 £1,275.90 NA NA Costs collected alongside
257
2010 RCT
2 All costs are mean initial treatment costs unless specified. Abbreviations: FS = foam sclerotherapy; CC = conservative care
1
3 Median (interquartile range)
2
4 Mean costs from group 3; severe varicose veins randomised to surgery or conservative care (SD).
3
5 Total undiscounted cost to NHS over 24 month period
6 It is clear from Table 125 that cost estimates obtained from the literature varied considerably, and as
7 such the GDG did not think these costs to be a reliable representation of UK practice. GDG members
8 attempted to gather cost information from their trusts, but there was inconsistency in how these
9 estimates were derived, so the GDG decided to construct cost estimates using a bottom up
10 approach.
11 Resource use was therefore based on GDG estimates. Where possible, unit costs for these resources
12 were collected from nationally available lists such as the NHS reference costs, or the PSSRU.
13 However, it was not always possible to find such costs, and in such cases unit costs were based on
14 GDG estimates. The cost estimates for the model are presented in the subsequent sections. The
15 estimates were intended to capture the differences between the costs, and therefore some aspects
16 (for example the cost of the initial appointments), have been omitted, as these are assumed not to
17 differ greatly between treatments. The cost of compression following treatment was limited to
18 bandages (applied immediately) and one pair of stockings, in line with the recommendation that
19 prolonged compression should not routinely be provided.
20 The majority of the unit costs provided below do not have an associated measure of uncertainty and
21 were therefore not modelled probabilistically. Probabilistic modelling was possible where unit costs
22 were taken from the NHS reference costs; a gamma distribution was fitted by manually adjusting the
23 standard error of the mean until the interquartile range of the distribution best matched that
24 reported for the unit cost. A gamma distribution was chosen so that the distribution was constrained
25 at zero (to avoid negative costs) and reflect the positive skew normally seen in cost data. Total costs
26 were subject to extensive deterministic sensitivity analyses.
27 Surgery
28 The breakdown of costs for surgery is provided in Table 126.
29 The GDG noted that greater perioperative care would be needed with surgery than with the other
30 treatments, thus a perioperative care estimate was included. No reliable figure was available to
31 reliably cost a few extra hours spent on a ward, thus the Band 5 time which would be spent looking
32 after a surgery patient was used as a proxy to capture the difference in perioperative care between
33 different treatments.

354
1 Table 126: Costs - Surgery

Hours/units Point
Components Unit cost Required estimate Distribution Source
62
Pre-op assessment (Band £82.00 0.25 hours £20.50 NA PSSRU
5)
62
Band 5 £82.00 1 hours £82.00 NA PSSRU
62
Band 5 (anaesthetic £82.00 1 hours £82.00 NA PSSRU
assistant)
62
Healthcare Assistant Band £20.00 1 hours £20.00 NA PSSRU
3
62
Consultant: surgical £136.00 1 hours £136.00 NA PSSRU
62
Consultant anaesthetist £136.00 1 hours £136.00 NA PSSRU
a
Disposables £250.00 1 £250.00 NA GDG estimate
Duplex £52.84 1 £52.84 Gamma NHS reference
77
costs
3
Stockings £5.99 1 £5.99 NA Cost of TED
stockings: NHS
supply chain
187
catalogue
Perioperative care
b 62
Band 5 £82.00 1.5 hours £123.00 NA PSSRU
Total £908.33
a
2 Includes gowns, surgical instruments, drapes, bandages and other disposable items
b
3 Based on 90mins pre-op where patient is looked after by ¼ nurse, 30 minutes post-op where patient is looked after by 1
4 nurse, additional 150mins post op ¼ nurse time
5 Endothermal techniques
6 The majority of the cost components for the two types of endothermal treatment (RFA & EVLA) were
7 considered to be the same as each other, with the only differences being the cost of the generators,
8 catheters and the controlled laser area required for EVLA. The cost of the catheter and generator
9 vary, as commercial companies have individual contracts with different trusts. The costs in Table 127
10 have been provided by commercial companies; due to the business sensitive nature of this
11 information individual company names have been removed.
12 Table 127: Catheter costs for EVLA and RFA

Procedure Company Generator cost Catheter cost
EVLA Company A Provided on long term loan free of charge £180 - £245
(List price is £15,000 - £22,000 but very rarely
bought)
Company B Provided on long term loan free of charge £200
(List price is £12,500 but very rarely bought)
RFA Company C Provided on long term loan free of charge £300
Company D Provided on long term loan free of charge £250 - £300
(List price is £10,000 but very rarely bought)
13
14 As indicated in Table 127, in the vast majority of cases the generator is loaned free of charge, usually
15 on the condition that the hospital carries out a certain amount of procedures per year. The cost of
16 the generator was therefore not considered in the analysis. The costs of the catheters were

355
1 approximated based on various estimates provided by commercial companies. Deterministic

2 sensitivity analyses will investigate the impact of changes in cost of catheters.
3 The GDG decided not to explicitly include the cost of the controlled laser area needed for EVLA in the
4 analysis, as the room would be used for a variety of laser procedures, and the cost per treatment
5 would be highly dependent on the number of procedures undertaken.
6 In practice, the two endothermal treatments (EVLA and RFA) compete directly with each other, and
7 this guideline assumes they have equal clinical effectiveness. The implication of this is that, in this
8 analysis, whichever of these two treatments is the cheapest will be cost-effective. However, due to
9 uncertainty around the costs, specifically that the RFA catheter is more expensive, but the EVLA
10 requires a laser controlled area, it is not straight forward to identify which of these treatments is
11 cheaper. For the purpose of this analysis it was assumed that once the cost of the laser controlled
12 area had been accounted for, the costs of the two treatments would be similar. The cost of
13 endothermal treatment used in the model was therefore £623.76. The breakdown of the costs is
14 provided in Table 128.
15 Table 128: Costs – Endothermal treatment

Hours/units Point
RFA catheter £300 1 £300 NA Table 127
EVLA catheter £200 1 £200 NA Table 127
a
Normal Saline £8.50 box of £0.43 1 £0.43 NA GDG estimate
20
62
Band 5 £82.00 0.75 hours £61.50 NA PSSRU
Healthcare Assistant Band 62
£20.00 0.75 hours £15.00 NA PSSRU
3
62
Consultant £136.00 0.75 hours £102.00 NA PSSRU
NHS reference
Duplex £52.84 1 £52.84 Gamma 77
costs
NHS supply
Stockings £5.99 1 £5.99 NA chain catalogue
187
RFA Total £623.76

£523.76 +
laser
EVLA Total
controlled
area
16 (a) includes gowns, procedure pack, surgical instruments, drapes, bandages, syringes and other disposable items
17 Foam sclerotherapy
18 The breakdown of costs for Sclerotherapy is provided in Table 129.
19 Table 129: Costs - Sclerotherapy

Hours/units Point
62
Consultant time £136.00 0.75 hours £102.00 NA PSSRU
62
Clinical nurse specialist £91.00 0.75 hours £68.25 NA PSSRU
time

356
Hours/units Point
a
Stockings (class II) £42.30 1 £42.30 NA NHS drug
186
tariff
Duplex £52.84 1 £52.84 Gamma NHS reference
77
costs
Total £315.39
1 (a) Includes gown, needles, bandages, syringes and other disposable items
2 Conservative care
3 The breakdown of costs for conservative care is provided in Table 130.
4 Based on clinical opinion, it was assumed that half of the patients who receive conservative care
5 return to their GP in the first year for further advice and reassurance. After the first year, the annual
6 costs were based on the assumption that the patient visits the practice nurse for a few routine
7 appointments over the course of the year, for advice and to be re-measured for stockings. We
8 acknowledge that in practice some of this measuring may be done by a pharmacist.
9 Table 130: Costs – Conservative care

Hours/units
Components Unit cost required Point estimate Source
First year costs
62
GP visits £30.00 0.5 £15.00 PSSRU
Annual costs
62
Practice nurse time £43.00 1.5 hours £64.50 PSSRU
a
Stockings (class II) £42.30 4 £169.20 NHS drug
186
tariff
First year total £248.70
Annual total £233.70
10 (a) based on an estimated lifespan of three months per stocking
11 Additional costs of retreatment
12 There are likely to be additional costs associated with re-treatment, over and above the cost of the
13 second treatment itself. The additional costs associated with a second treatment episode were
14 based on clinical opinion, and are provided in Table 131.
15 Table 131: Additional costs for retreatment

Hours/units Point
Components Unit cost required estimate Distribution Source
62
GP visit £30.00 2.5 £75.00 NA PSSRU
OP 1st attendance £165.49 1 £165.49 Gamma NHS reference
77
vascular surgery costs
OP 2+ attendance vascular £123.28 1 £123.28 Gamma NHS reference
77
surgery costs
Duplex scan £52.84 1 £52.84 Gamma NHS reference
77
costs
Total £416.61
239
16 Note the resource components here have been replicated from the aforementioned on-going HTA project

357
1 L.2.4 Sensitivity analyses

2 The sensitivity analyses described in Table 132 were undertaken to explore the effect of different
3 parameter inputs and assumptions on the results of the model. The results of all sensitivity analyses
4 are presented in section L.3.1.

358
1 Table 132: Alternative values and descriptions for deterministic sensitivity analyses
Analysis Parameter Description of sensitivity analysis Values Comment
244
SA1 Baseline recurrence Some members of the GDG felt that the baseline 0.00384 Recurrence rate from Shadid2012 (lowest
rate recurrence rate following surgery, to which the recurrence rate from included trials)
relative effects from the NMA were applied, was
too high. The baseline rate was calculated from 0.01548 Recurrence rate from Carradice2011
48
clinical recurrence reported in randomised trials, (highest recurrence rate from included trials)
and could be higher than those observed in UK
practice for several reasons. Sensitivity analyses
employ different baseline rates of recurrence
SA2 Endothermal The need for top up treatment and cost of 10% require top up The need for top up treatment will be higher,
treatment without procedure is likely to be different if concurrent treatment and the cost of procedure will be slightly
concurrent phlebectomy is not carried out. This sensitivity Cost of procedure: lower; clinical evidence does not distinguish
phlebectomy analysis evaluates the cost effectiveness of £272.27 + catheter between endothermal with/without
endothermal treatment without phlebectomies phlebectomy thus probability of clinical
compared to the other treatments recurrence remains unchanged
359
SA3 Utility for The data used for utility of conservative care 1 year adjusted The adjusted value reported at one year is
conservative care includes a sharp increase in utility at 2 years. This difference between extrapolated over the 5 year time horizon
increase is dramatic and unexpected, thus in this utility of conservative
SA we omit the two year data care and surgery: -0.1
SA4 GSV + SSV Treating an additional truncal vein will extend S: £1,119.12 Cost increase compared to base case due to
procedure time and have an impact on total F: £329.84 an extra 15 minutes treatment time
procedure cost E: £691.27
SA5 Time horizon The time horizon is shortened to avoid 3 years 3 years is the longest follow-up of the trials
extrapolation past the maximum follow-up time included in the NMA
found in the data
SA6 Costs Various SAs to investigate how robust the model Relative costs The GDG had no strong indication of what
is to the costs of treatment, around which there manipulated and plausible ranges for treatment costs were;
is great uncertainty costs for therefore threshold analyses conducted
conservative care within an arbitrary but wide interval
reduced
SA6b Cost of catheters for These SAs investigate how robust the model is to EVLA catheters: Maximum and minimum values (as at
Analysis Parameter Description of sensitivity analysis Values Comment
endothermal the costs of the endothermal catheters, around £180-£245 October 2012) provided by commercial
treatment which there is great variability RFA catheters: £250- companies
£300
Top-up treatment These SAs explore the impact of the GDG S: 0-5% Threshold sensitivity analyses within plausible
SA7 rates estimate of the proportion of patients who will F: 10-100% range suggested by GDG members
need top up treatment
E: 0-5%
Proportions receiving The proportion receiving a conservative care 75% Arbitrary, wide ranging values.
SA8 conservative care following clinical recurrence is varied (the 50%
following clinical remainder receive a second treatment episode)
recurrence (instead of
re-treatment)
SA9 Proportions receiving The type of retreatment a patient would receive S:20%; F:10%, E:70% Sensitivity analyses use alternative
each type of would be highly dependent on the nature of the S:5%; F:5%, E:90% proportions suggested by individual GDG
treatment during the recurrence and further patient characteristics. members.
second treatment This SA investigates the impact of the S:10%; F:45%, E:45%
360
episode assumptions around the proportions of patients S:15%; F:80%, E:5%

receiving each type of retreatment S:10%; F:60%, E:30%
S:10%; F:50%, E:40%
1 Abbreviations: F = Foam; S= Surgery; E= endothermal
3
1 L.2.5 Bilateral treatment

2 The model base case only considered unilateral patients, yet consideration should also be given to
3 treatment of bilateral patients. The model does not lend itself to bilateral analysis, as significant
4 assumptions would have to be made around whether top-up treatment was complete in one or two
5 legs, whether clinical recurrence was experienced in one or two legs, and whether both legs were
6 retreated. Furthermore, utility increases and decrements as used in the unilateral model would no
7 longer be applicable. The GDG therefore decided that a cost-comparison was the preferred method
8 to analyse the treatment of bilateral patients.
9 In order to calculate costs of bilateral surgery and endothermal treatment, a proportional increase
10 was applied to the unilateral costs documented in Table 126 and Table 128. A variety of scenarios
11 were presented in which this proportional increase was varied, in order to capture uncertainty. The
12 maximum that bilateral treatment could be expected to cost would be 200% of the cost of unilateral
13 treatment, as would be the case if both legs were to be treated completely separately. Therefore the
14 maximum cost of bilateral treatment was assumed to be 200% of the costs specified in Table 126
15 Table 128. The NHS reference costs77 indicate that for day case procedures, bilateral treatment costs
16 112% of the cost of unilateral treatment; this was taken as the minimum proportional increase in
17 costs.
18 The bilateral cost of foam sclerotherapy was assumed to be twice the cost of unilateral treatment.
19 This is because there are consensus recommendations on the maximum amount of sclerosant foam
20 which should be given per session.36 The recommended maximum volume per session is 10ml, and
21 the recommended average is lower, between 2 and 8ml of sclerosant foam. In many cases this would
22 prevent treatment of both legs in one sitting; indeed the recommendations add that it is advisable to
23 limit the amount of sclerosant foam given per session, even if this means the patient requires more
24 than one treatment. As the costs of initial appointment have been omitted, treating the legs
25 separately can be considered equivalent to two unilateral cases from a costing point of view.
26 The cost of conservative care for bilateral treatment was calculated by doubling the number of
27 stockings required. The number of GP appointments and practice nurse time was assumed to stay
28 the same as with unilateral treatment.
29 The results of the cost comparison are documented in section L.3.2.
30 L.2.6 Computations
31 The model was constructed in Microsoft Excel and was evaluated by cohort simulation.
32 L.2.6.1 Calculating cost effectiveness
33 The widely used cost-effectiveness metric is the incremental cost-effectiveness ratio (ICER). This is
34 calculated by dividing the difference in costs associated with two alternatives by the difference in
35 QALYs. The decision rule then applied is that if the ICER falls below a given cost per QALY threshold
36 the result is considered to be cost effective. If both costs are lower and QALYs are higher the option
37 is said to dominate and an ICER is not applicable.
38
Costs( B) − Costs( A)
ICER = • Cost-effective if:
QALYs( B) − QALYs( A)
ICER < Threshold
Where: Costs/QALYs(X) = total costs/QALYs for option X

361
1 When there are more than two comparators, as in this analysis, options must be ranked in order of
2 increasing cost then options ruled out by dominance or extended dominance before calculating ICERs
3 for the remaining options.
4 It is also possible, for a particular cost-effectiveness threshold, to re-express cost-effectiveness

5 results in term of net monetary benefit (NMB). This is calculated by multiplying the total QALYs for a
6 comparator by the threshold cost per QALY value (for example, £20,000) and then subtracting the
7 total costs (formula below). The decision rule then applied is that the comparator with the highest
8 NMB is the most cost-effective option at the specified threshold. That is the option that provides the
9 highest number of QALYs at an acceptable cost.
10
Net Benefit ( X ) = (QALYs ( X ) × λ ) − Costs ( X ) • Cost-effective if:
highest net benefit
Where: Costs/QALYs(X) = total costs/QALYs for option X; λ = threshold
11 Both methods of determining cost effectiveness will identify exactly the same optimal strategy. For
12 ease of computation NMB was used to identify the optimal strategy in the probabilistic analysis
13 simulations.
14 The probabilistic analysis was run for 10,000 simulations. Each simulation, total costs and total QALYs
15 were calculated for each strategy. Net benefit was also calculated and the most cost-effective option
16 identified (that is, the one with the highest net benefit), at a threshold of £20,000 per QALY gained.
17 The results of the probabilistic analysis were summarised in terms of mean costs, mean QALYs and
18 mean net benefit for each treatment option, where each was the average of the simulated estimates.
19 The option with the highest mean net benefit (averaged across the simulations) was the most cost-
20 effective at the specified threshold. The percentage of simulations where each strategy was the most
21 cost-effective gives an indication of the strength of evidence in favour of that strategy being cost-
22 effective.
23 Results are also presented graphically where mean total costs and mean total QALYs for each
24 treatment option is plotted. Comparisons not ruled out by dominance or extended dominance are
25 joined by a line on the graph where the slope represents the incremental cost-effectiveness ratio, the
26 magnitude of which is labelled.
27 L.2.7 Model validation

28 The model was developed in consultation with the GDG; model structure, inputs and results were
29 presented to and discussed with the GDG for clinical validation and interpretation.
30 The model was systematically checked by the health economist undertaking the analysis; this
31 included inputting null and extreme values and checking that results were plausible given inputs. The
32 model was peer reviewed by an experienced health economist who had not been involved in the
33 guideline; this included systematic checking of the model calculations.
34 L.2.8 Interpreting results

35 NICE’s report ‘Social value judgements: principles for the development of NICE guidance’ sets out the
36 principles that GDGs should consider when judging whether an intervention offers good value for
37 money. In general, an intervention was considered to be cost effective if either of the following
38 criteria applied (given that the estimate was considered plausible):
39 • The intervention dominated other relevant strategies (that is, it was both less costly in terms of
40 resource use and more clinically effective compared with all the other relevant alternative
41 strategies), or

362
1 • The intervention costs less than £20,000 per quality-adjusted life-year (QALY) gained compared
2 with the next best strategy.
3 L.3 Results
4 Detailed results are presented over the next few pages for the base case and various sensitivity
5 analyses. As the results of the deterministic and probabilistic analysis were comparable, all results
6 reported below are means from the probabilistic analysis unless otherwise specified.
7 Table 133 and Figure 161 show the base case results. Both conservative care and surgery were
8 dominated, as they provided less QALYs at increased cost when compared to endothermal
9 treatment. As these strategies are dominated, they are not further considered in the incremental
10 analysis and the ICER is not calculated.
11 Table 133: Mean base case results (probabilistic)

Mean per patient NMB at threshold Rank at threshold Probability of
a
Treatment QALYs Cost of £20,000 of £20,000 being CE
Conservative care 3.55 £1,102 £69,965 4 4%
Surgery 3.69 £1,222 £72,554 3 3%
Foam 3.67 £718 £72,681 2 23%
sclerotherapy
Endothermal 3.72 £869 £73,484 1 71%
12 (a) For interpretation of the probability of being cost-effective see section L.2.6.1.
13 Figure 161: Cost effectiveness plane showing incremental cost and QALYs per patient expected
14 with each strategy (Base case, probabilistic analysis)
15
£200.00
£100.00
£-
Incremental Cost
0.00 0.05 0.10 0.15 0.20

Foam
-£100.00
Endothermal
-£200.00 Conservative care
-£300.00 Surgery
ICER=£3,161
-£400.00
-£500.00
Incremental QALYs
16
17 In the base case analysis, the strategy which provided the most QALYs was endothermal treatment.
18 However, this came at an additional cost compared to foam sclerotherapy. Using the mean costs and
19 QALYs generated over the probabilistic sensitivity analysis, the ICER of endothermal treatment
20 compared to foam was £3,161 which is below the NICE threshold of £20,000 per QALY gained.
21 Endothermal treatment had a probability of being cost-effective of 71%, followed by foam which had
22 a lower chance of being the most cost-effective option of 23%.

363
1 Disaggregating the results of the analysis by cost and QALYs allows us to examine the impact of key
2 components of the model on the overall results. The QALYs associated with the initial treatment
3 episode are the same for each treatment, therefore we know that that the difference in total QALYs
4 is driven by the reduction in QoL associated with recurrence. Endothermal treatment has the lowest
5 probability of recurrence per cycle, thus the results of the model align with our expectation that this
6 treatment would lead to the highest total QALYs.
7 Table 134 provides the breakdown of total cost (the probabilistic costs of the initial treatment
8 episode are comparable to the deterministic estimates in Table 126 –Table 130). It shows that whilst
9 the costs due to recurrent treatment do differ (Note – this is the cost of retreatment averaged across
10 all patients), the difference in total costs between treatment methods is mainly due to the initial
11 treatment costs. Sensitivity analyses explored the impact of changes in the treatment costs – see
12 below.
13 Table 134: Breakdown of total costs (probabilistic base case)

Cost of initial treatment Cost of recurrent
a
Treatment episode treatment Total cost
b
Conservative care N/A N/A £1,102
Surgery £924 £299 £1,222
Foam sclerotherapy £378 £340 £718
Endothermal £639 £230 £869
14 (a) This is the average cost of treatment and management of recurrent varicose veins weighted by the proportion of
15 individuals who will require this, therefore this represents the expected per person cost of recurrence.
16 (b) Initial and recurrent treatment costs are not applicable for conservative care as this was modelled separately as an on-
17 going management technique
18
19 The number of clinical recurrences over time is shown in Figure 162 for each treatment. The GDG felt
20 these values were acceptable, but noted that it was difficult to judge face validity of these results, as
21 the majority of the GDG members do not see all clinical recurrence cases, only those patients who
22 are to be retreated. Sensitivity analyses investigated the impact of changing the level of clinical
23 recurrence.
24 L.3.1 Sensitivity analyses

25 Sensitivity analyses were run probabilistically unless otherwise stated. In all analyses endothermal
26 treatment was recorded as the optimal strategy. Table 136 summarises the results of these analyses.
27 Throughout all of the probabilistic sensitivity analyses, neither the probability of conservative care or
28 surgery being the optimal strategy rose above 5%. Overall, the sensitivity analyses demonstrated that
29 the results of this analysis were robust to changes in key assumptions, recurrence rates, and
30 substantial changes in relative costs.
31

364
1 Figure 162: Clinical recurrence over time
3 L.3.2 Bilateral treatment

4 The results of the cost comparison are presented in Table 135. The GDG discussed the figures in this
5 table alongside the bilateral results, and concluded that endothermal treatment is likely to be the
6 cost-effective treatment strategy for bilateral treatment.
7 Table 135: Bilateral treatment cost comparison (deterministic)

Cost of unilateral treatment Multiplier Cost of bilateral treatment
Conservative care
a a
£234 NA £403
Surgery
£924 112% £1,035
120% £1,109
140% £1,294
160% £1,479
180% £1,663
200% £1,848
Endothermal
£640 112% £716
120% £767
140% £895
160% £1,023
180% £1,151
200% £1,279
Foam sclerotherapy
£378 200% £757
8 (a) represents annual cost

365
1 Table 136: Results of sensitivity analysis

Mean QALYs per patient Mean costs per patient Optimal Probability CE at
Sensitivity analysis CC S FS E CC S FS E strategy £20,000 threshold
SA1 : Baseline recurrence rate
SA1a: Lowest baseline 3.62 3.75 3.74 3.77 £1,102 £1,067 £548 £746 Endothermal 74%
recurrence
SA1b: Highest baseline 3.48 3.61 3.59 3.66 £1,102 £1,402 £901 £1,015 Endothermal 74%
recurrence:
SA2 – SA5: Assumptions
SA2: Endothermal treatment 3.55 3.69 3.67 3.72 £1,102 £1218 £713 £822 Endothermal 73%
does not include phlebectomy
SA3: Utility for conservative 3.25 3.69 3.67 3.72 £1,102 £1224 £722 £871 Endothermal 75%
care extrapolated from 1 year
value
366
SA4: GSV + SSV 3.55 3.69 3.67 3.72 £1,102 £1355 £805 £943 Endothermal 72%
SA5: 3 year time horizon 2.19 2.32 2.31 2.33 £699 £1085 £569 £761 Endothermal 62%
SA6: Costs (deterministic)
SA6i: Surgery, sclerotherapy, 3.56 3.69 3.68 3.73 £558 £687 £432 £789 Endothermal N/A
conservative care costs
reduced by 50%, cost of
endothermal remains as base
case
SA6ii: Below knee standard 3.56 3.69 3.68 3.73 £511 £1,179 £653 £828 Endothermal N/A
stockings for conservative care
(£11 instead of £42 per pair)
SA6iii: Below knee standard 3.56 3.69 3.68 3.73 £211 £1,162 £635 £816 Endothermal N/A
stockings and no practice nurse
time for conservative care
SA6iv: Threshold cost analysis The cost of endothermal treatment would have to increase by £681, and the cost of all other treatments remain the same in order to
of increase in cost of no longer be considered cost-effective. In this instance, foam would be the optimal strategy.

Mean QALYs per patient Mean costs per patient
Optimal Probability CE at
Sensitivity analysis CC S FS E CC S FS E strategy £20,000 threshold
endothermal treatment
SA6b: Cost of catheters for endothermal treatment
£180 3.55 3.69 3.67 3.72 £1,102 £1,209 £703 £738 Endothermal 74%
£395 3.55 3.69 3.67 3.72 £1,102 £1,233 £730 £970 Endothermal 67%
SA7: Top-up treatment rate - threshold analyses (deterministic)
Surgery 0-10% N/A Endothermal N/A
Foam sclerotherapy 10-100% N/A Endothermal N/A
Endothermal 0-10% N/A Endothermal N/A
SA8: Proportions receiving conservative care following first recurrence instead of retreatment
SA8a: 75% 3.53 3.66 3.64 3.70 £1,102 £1,159 £648 £820 Endothermal 72%
SA8b: 50% 3.54 3.68 3.66 3.71 £1,102 £1,191 £682 £844 Endothermal 72%
SA9: Proportions receiving each type of treatment during the second treatment episode (deterministic)
367
S:20%; F:10%; E:70% 3.56 3.69 3.68 3.73 £1,102 £1,235 £714 £869 Endothermal N/A
S:10%; F:45%;E:45% 3.56 3.69 3.68 3.73 £1,102 £1,208 £685 £849 Endothermal N/A

1 L.4 Discussion
2 L.4.1 Summary of results
3 This analysis found that endothermal treatment is the most clinically and cost effective treatment
4 strategy for people with varicose veins (note - EVLA and RFA were considered together in the model,
5 and the results do not distinguish between these two endothermal techniques). This conclusion was
6 robust to a wide range of sensitivity analyses, demonstrating that although uncertainty surrounds
7 model inputs, variation within reasonable ranges does not change the results.
8 An area of particular uncertainty was the costs, yet sensitivity analyses revealed that the model is
9 robust to changes in relative costs. For example, even if the differences in costs have been
10 underestimated, endothermal treatment would remain the optimal strategy even if the costs of all
11 the other treatments are half of what we estimated in the base case. If the costs of surgery,
12 sclerotherapy and conservative care remain as specified in the base case, endothermal treatment
13 remains cost effective even with increases in cost of up to £681.
14 L.4.2 Limitations and interpretation

15 The clinical review was not designed to distinguish between different types of endothermal
16 treatment and as such the results presented here do not make any distinction between RFA and
17 EVLA, or any further variation within these treatment modalities. Whilst the decision to treat the
18 various endothermal treatments as one combined treatment was based on GDG consensus, this
19 could be considered a limitation of the analysis.
20 A further limitation of the model is the specific population to which it applies. The interventions
21 considered are only true comparators when considering patients for whom all four treatments are a
22 possibility, and in practice this may only be a small proportion of the varicose veins population. If
23 endothermal treatment is not suitable for a patient then foam sclerotherapy is the cost-effective
24 option, and if foam is not suitable either, surgery is the optimal strategy. Further issues of
25 generalizability are discussed in section L.4.3.
26 An additional drawback of this analysis is that the estimates of rates of top-up treatment were based
27 on GDG estimates, but the clinical recurrence data was based on trial outcomes. Depending on how
28 clinical recurrence was reported, it is likely that in some instances the trials recorded what would be
29 deemed here as a need for top-up treatment as clinical recurrence. The implication of this is that
30 some recurrences may have been double counted. This said, sensitivity analyses revealed that the
31 model was robust to changes in top-up rates and in clinical recurrence rates, therefore this drawback
32 represents only a minor limitation.
33 Assumptions were made around top-up treatments, as well as modality of retreatment, which could
34 potentially be considered as limitations to the model. However sensitivity analyses revealed that
35 reasonable changes in these assumptions did not impact the results.
36 The assumptions of the network meta-analysis model necessitated a constant hazard of clinical
37 recurrence over time. This represents a restriction of the analysis, yet this assumption was deemed
38 reasonable over the relatively short time horizon of the model. Ideally, utility data would have been
39 included which reflected treatment specific improvements in quality of life, however as discussed
40 earlier, reliable data to reflect this could not be found. Use of the PROMs data brings its own
41 limitations, such as the potential for sampling bias.
42 Finally, this analysis does not attempt to answer the questions of the optimal timing of intervention,
43 or the optimal choice of treatment at each stage of the disease. We initially hoped to address these

1 questions, but reliable data were not available. Consequently, conclusions are applicable to the
2 general varicose veins population, with no separate consideration of subgroups. Input data were
3 collected from individuals at various stages of varicose veins severity, and we cannot be certain that
4 interventional treatment is cost-effective in each subgroup.
5 L.4.3 Generalisability to other populations / settings

6 The conclusions of this analysis are expected to apply to the UK adult varicose veins population.
7 Whilst varicose veins are only rarely seen in children, the results of this analysis are unlikely to be
8 generalisable to this population.
9 Endothermal treatment and foam sclerotherapy were assumed to take place in an outpatient setting
10 and surgery as a day case procedure. The analysis has not considered different settings of treatment,
11 for example endothermal treatment as a day case procedure or surgery as an inpatient procedure.
12 Nevertheless, sensitivity analysis did show that the optimal strategy was fairly robust to increases in
13 the cost of endothermal treatment and so if outpatient endothermal treatment was not considered
14 suitable for a patient, day case endothermal treatment may represent a cost-effective alternative.
15 L.4.4 Comparisons with published studies

16 Gohel and colleagues (2010)106 present the only analysis published at present which compares all the
17 treatments included in this analysis in a UK setting. Whilst day case surgery offers the highest net
18 benefit, the authors conclude that RFA or EVLA performed as an outpatient procedure, or surgery
19 performed as a day case procedure, are likely to be cost-effective treatments, as differences in costs
20 and QALYs are small. The suggestion that RFA and EVLA are cost-effective aligns with our findings
21 that endothermal treatment is the optimal treatment strategy.
22 L.4.5 Conclusion = evidence statement

23 According to the results of this original economic model based on the current clinical evidence
24 review and GDG input, it is likely that endothermal treatment is the cost effective strategy for people
25 in whom all treatments are suitable. When endothermal treatment is not deemed suitable for a
26 patient, foam sclerotherapy is likely to be the optimal strategy. Surgery represents the optimal
27 choice if neither endothermal treatment nor foam sclerotherapy are thought suitable. This evidence
28 is directly applicable, with minor limitations.
29 L.4.6 Implications for future research

30 A major issue which remains to be addressed is the question of which patients should be treated,
31 which is closely related to the question of the optimal timing of intervention. To answer such a
32 question would require data on the natural progression of varicose veins, i.e. what happens to
33 patients who are not treated. Such data is unlikely to emerge from future research due to ethical
34 considerations.
35 Future research into the effectiveness of each intervention at each stage of the disease would be a
36 step towards solving this issue. If this data was available, future analyses could investigate whether
37 different treatment strategies are optimal at different stages of the disease, and potential
38 efficiencies could be realised.

Network meta-analysis
1 Appendix M: Network meta-analysis

2 M.1 Network meta-analysis code
3 # Binomial likelihood, cloglog link
4 # Random effects model for multi-arm trials
5 model{ # *** PROGRAM STARTS
6 for(i in 1:ns){ # LOOP THROUGH STUDIES
7 w[i,1] <- 0 # adjustment for multi-arm trials is zero for control arm
8 delta[i,1] <- 0 # treatment effect is zero for control arm
9 mu[i] ~ dnorm(0,.0001) # vague priors for all trial baselines
10 for (k in 1:na[i]) { # LOOP THROUGH ARMS
11 r[i,k] ~ dbin(p[i,k],n[i,k]) # Binomial likelihood
12 # model for linear predictor
13 cloglog(p[i,k]) <- log(time[i]) + mu[i] + delta[i,k]
14 rhat[i,k] <- p[i,k] * n[i,k] # expected value of the numerators
15 #Deviance contribution
16 dev[i,k] <- 2 * (r[i,k] * (log(r[i,k])-log(rhat[i,k]))
17 + (n[i,k]-r[i,k]) * (log(n[i,k]-r[i,k]) - log(n[i,k]-rhat[i,k]))) }
18 # summed residual deviance contribution for this trial
19 resdev[i] <- sum(dev[i,1:na[i]])
20 for (k in 2:na[i]) { # LOOP THROUGH ARMS
21 # trial-specific LOR distributions
22 delta[i,k] ~ dnorm(md[i,k],taud[i,k])
23 # mean of LOR distributions, with multi-arm trial correction
24 md[i,k] <- d[t[i,k]] - d[t[i,1]] + sw[i,k]
25 # precision of LOR distributions (with multi-arm trial correction)
26 taud[i,k] <- tau *2*(k-1)/k
27 # adjustment, multi-arm RCTs
28 w[i,k] <- (delta[i,k] - d[t[i,k]] + d[t[i,1]])
29 # cumulative adjustment for multi-arm trials
30 sw[i,k] <- sum(w[i,1:k-1])/(k-1)

1 }
2 }
3 totresdev <- sum(resdev[]) #Total Residual Deviance
4 d[1]<-0 # treatment effect is zero for reference treatment
5 # vague priors for treatment effects
6 for (k in 2:nt){ d[k] ~ dnorm(0,.0001) }
7 sd ~ dunif(0,5) # vague prior for between-trial SD
8 tau <- pow(sd,-2) # between-trial precision = (1/between-trial variance)
9 # Provide estimates of treatment effects T[k] on the natural (probability) scale
10 # Given a Mean Effect, meanA, for 'standard' treatment A,
11 # with precision (1/variance) precA, over a time period timeA
12 A ~ dnorm(meanA,precA)
13 for (k in 1:nt) { cloglog(T[k]) <- log(timeA) + A + d[k] }
14 # pairwise HRs and LHRs for all possible pair-wise comparisons, if nt>2
15 for (c in 1:(nt-1)) {
16 for (k in (c+1):nt) {
17 lhr[c,k] <- (d[k]-d[c])
18 log(hr[c,k]) <- lhr[c,k]
19 }
20 }
21 # ranking on relative scale
22 for (k in 1:nt) {
23 rk[k] <- rank(d[],k) # assumes events are “bad”
24 best[k] <- equals(rk[k],1) #calculate probability that treat k is best
25 }
26 } # *** PROGRAM ENDS

27

1 M.2 Baseline model code (meta-analysis of surgery trial arms)

2
3 # Random effects probability model
4 model{
5 for( i in 1 : 8) {
6 r[i] ~ dbin(p[i],n[i]) #Likelihood
7 cloglog(p[i]) <- b[i] + log(time[i]) #cloglog of response
8 b[i] ~ dnorm(d,prec) #Random effects model
9 rhat[i] <- p[i] * n[i] # expected value of the numerators
10 #Deviance contribution
11 dev[i] <- 2 * (r[i] * (log(r[i])-log(rhat[i]))
12 + (n[i]-r[i]) * (log(n[i]-r[i]) - log(n[i]-rhat[i])))
13 }
14 b.new~dnorm(d,prec) #predictive dist. (log-odds)
15 resdev <- sum(dev[])
16 d ~ dnorm(0.0,1.0E-6) #vague prior for mean effect
17
18 cloglog(T1) <- b.new +log(1)
22
23 #logit(T.new) <- b.new
24 #sd <- 1/sqrt(prec) # gamma prior for RE precision
25 #prec ~ dgamma(0.001,0.001)
26 sd ~ dunif(0,5) # uniform prior for RE st dev
27 prec <- pow(sd,-2)
28 }
29
30

Research recommendations
1 Appendix N: Research recommendations

2
3 The Guideline Development Group has made the following recommendations for research, based on
4 its review of evidence, to improve NICE guidance and patient care in the future.
5 N.1 Key future research recommendations (FRR)

6 N.1.1 Natural history of varicose veins
7 In people with varicose veins at CEAP (Clinical, etiological, anatomical and pathophysiological) stage
8 C2 or C3, what are the factors that influence progression of the disease to CEAP stages C5 or C6?
9 Why this is important
10 The evidence review for the guideline showed a lack of high-quality evidence on the progression of
11 varicose veins from CEAP stage C2 or C3 to more serious varicose veins disease. A large observational
12 prospective cohort study, similar to the Framingham or BONN veins studies, should be undertaken.
13 The study should recruit patients with C2 and C3 disease and follow the progress of their disease
14 over a number of years. Consideration should be given to including a genetic component in the study
15 because genetic factors have not been studied on a large scale. The results of such a study should
16 help to more accurately identify which patients are at risk of developing more serious disease so that
17 interventions can be offered at an early stage to those who will benefit most.
18 Criteria for selecting high-priority research recommendations

Criterion Explanation
Importance to If the research were to identify clear factors which were indicators for progression to
patients or the more serious disease, those patients who are most at risk could be identified at an earlier
population stage and either monitored more closely or treated at an earlier stage. This would then
potentially lead to more efficient use of resources.
Relevance to This research is of medium relevance to the NICE guidelines. The research is relevant but
NICE guidance is not key to future updates as a recommendation was able to be produced in its
absence.
Relevance to the The research is relevant to the NHS, depending on the results it may allow the
NHS identification of people at risk, and hence may change the allocation of resources.
National This research is not relevant to a national priority area.

priorities
Current The evidence found from the systematic reviews in the guideline were mainly case
evidence base control and small cohort studies. These are not sufficient to identify all the risk factors. In
addition, no large scale study has looked to determine if there is a genetic component
involved in the progression of varicose veins.
Equality The research would not discriminate against any group.
Feasibility The proposed research is a long term project and does have a substantial cost associated

with it. However, it was the opinion of the GDG that the potential benefits of the
research would outweigh the costs. The issue of treatment needs to be considered. It
would not be ethical to prevent patients from having treatment as their disease
worsened. Treatment should be taken into account in the research design.
Other comments None
Study design Prospective cohort study
2 N.1.2 Interventional treatment for those with CEAP stage C6 disease (leg ulcers) and varicose
3 veins
4 Does the early interventional treatment of superficial venous reflux together with compression
5 therapy improve wound healing and result in greater cost effectiveness compared with compression
6 therapy alone in patients with chronic venous ulceration?
8 Chronic venous leg ulcers are a common major cause of morbidity. Quality of life for patients with
9 venous leg ulcers is substantially reduced by discomfort and social isolation resulting from odour and
10 wound discharge. The social and personal impact of chronic venous leg ulceration is therefore
11 considerable.
12 Only one study has been completed in which surgery and compression were compared with
13 compression alone. This showed improvement in the rates of ulcer recurrence. It would now be
14 suitable to consider endovenous interventional techniques which, being a minimally invasive
15 procedure, are more acceptable to patients.
16 At present ulceration is often managed with compression, despite poor success rates. A high-quality
17 large-scale randomised trial evaluating outcomes after early interventional treatment compared with
18 compression therapy is needed.

Importance to This study is important to those patients with CEAP stage C6 disease whose quality of life
patients or the is substantially reduced by discomfort and social isolation resulting from odour and
population wound discharge. The social and personal impact of chronic venous leg ulceration is
therefore considerable.
Relevance to Results would influence recommendations regarding best management of severe venous
NICE guidance dysfunction and with the ESCHAR study would influence the planning of venous services.
Relevance to the Leg ulceration due to superficial venous reflux is a major cause of morbidity and a huge
NHS drain on NHS resources. Improved management techniques may influence service
delivery and ultimately strategic planning.
National None
priorities
Current The RCT ESCHAR study compared surgery and compression with compression alone but
evidence base it might now be suitable to consider endovenous interventional techniques which being
a minimally invasive procedure is more acceptable to patients and may be delivered

without delay.
Equality None identified.
Feasibility The proposed research could be carried out within a realistic timescale and at an
acceptable cost. No ethical or technical issues?
Other This study has recently been submitted in the form of The Early Venous Reflux Ablation
comments (EVRA) ulcer trial to the National Institute for Health Research. In the ESCHAR study, no
improvement in ulcer healing rates was seen, but operative intervention was delayed for
a median time of 7 weeks. Recruitment period : 24 months. Study duration : 48 months.
Study design Multi-centred randomised controlled trial.
2 N.1.3 Truncal treatment with or without concurrent tributary treatment
3 Research Question
4 What is the clinical and cost effectiveness of concurrent phlebectomies for varicose tributaries during
5 truncal endothermal ablation for varicose veins compared with:
6 • truncal endothermal ablation without concurrent phlebectomies
7 • truncal endothermal ablation with subsequent phlebectomies, if needed, 6–12 weeks later.
9 Conventional truncal stripping under general anaesthetic involves synchronous phlebectomies of

10 varicose tributaries, and in ultrasound-guided foam sclerotherapy truncal and tributary veins are
11 treated concurrently. In contrast, endothermal ablation may be performed alone to obliterate
12 truncal incompetence, or synchronously with phlebectomies, and current practice varies.
13 Synchronous tributary treatment ensures a single treatment episode, and the removal of all
14 symptomatic varicosities leads to a better immediate quality of life, but this takes longer and thus
15 may be associated with increased morbidity. Deferred tributary treatment may reduce morbidity,
16 and also mean that some patients do not need tributary treatment (or need fewer tributary
17 treatments on smaller veins). However, it involves two interventions for patients who need tributary
18 treatment. Omitting tributary treatments entirely ensures a single treatment episode, but it is
19 unclear whether remaining varicosities will persist and impair quality of life.
20 At present there is limited evidence from one small-scale (n=50) study on the use and timing of
21 tributary treatments after truncal endothermal ablation treatment. There is a need for practice to be
22 based on empirical evidence from a large and sufficiently powered RCT comparing all three main
23 intervention options (no tributary treatment, concurrent tributary treatment and delayed tributary
24 treatment).

Importance to If the trial showed a benefit of tributary treatment during or after treatment this would
patients or the lead to altered guidance recommending tributary treatment during or after
population interventional treatment. This would improve patients’ quality of life.
Relevance to This research is of medium importance to the NICE guideline, as the research is relevant
NICE guidance to the recommendations in the guideline but the research recommendations are not key
to future updates.

Relevance to the The impact of this research on the NHS is minimal. If the research identified a benefit
NHS with tributary treatment during or after treatment a change in recommendation would
be required which would lead to a change in practice in the NHS and could reduce costs.
National This research is not relevant to any known national priority areas.
priorities
Current The evidence for this section was reviewed in chapter 9e. Only 1 randomised controlled
evidence base trial was identified in this area. This was not prone to serious bias (unblinded, but clear
allocation concealment and no attrition bias) but was possibly underpowered with high
levels of imprecision for some outcomes, leading to these outcomes being graded as very
low. In addition, this RCT had a short follow-up of only 6 weeks for concurrent tributary
treatments vs. no tributary treatment.
Equality The research does not address equality issues as all people will be able to access the
intervention.
Feasibility The research is expected to be able to be carried out within a realistic timescale and
acceptable cost. It is not expected that there would be any ethical or technical issues.
Other comments None
Study design Randomised controlled trial
2 N.1.4 Compression as a management option
3 What is the clinical and cost effectiveness of compression hosiery versus no compression for the
4 management of symptomatic varicose veins?
6 Compression hosiery is widely used as first-line treatment for symptomatic varicose veins. In some
7 areas of the UK a period of hosiery use is a precursor to referral to secondary care.
8 Discomfort and difficulty in application may cause people to stop wearing compression hosiery or
9 wear it only occasionally. The current evidence for the benefit of compression hosiery is weak. There
10 is little evidence of an impact on symptom relief or an improvement in quality of life. It is therefore
11 not possible to calculate the cost effectiveness of compression hosiery.
12 A multicentre trial randomising compression hosiery versus no compression in patients with

13 symptomatic varicose veins is needed. The trial should evaluate quality of life, including symptom
14 reduction, and measure adherence with compression hosiery. In addition the trial should investigate
15 the impact of compression on disease progression and the need for subsequent intervention.

Importance to The research is important to patients and, if results showed a benefit for compression,
patients or the clinicians would be confident they were being offered a clinically proven treatment
population option.
Relevance to This research is highly relevant to NICE guidance. The answer to this question may
NICE guidance change the guidance and the way that varicose veins are treated. The poor quality
current evidence and relatively high costs mean that compression has not been

recommended, but if the research were to identify that symptoms of varicose veins were
substantially reduced the recommendation may change. Compression might then
provide an effective non-interventional management strategy.
Relevance to the What would be the impact on the NHS and (where relevant) the public sector of any new
NHS or altered guidance (for example, financial advantage, effect on staff, impact on strategic
planning or service delivery)?
The research could potentially reduce the variation in practice within the NHS. If the
results showed that compression hosiery was effective for the management of varicose
veins this would provide a non-interventional management strategy. Conversely, if the
research was clear that compression stockings showed little benefit, the NHS could then
stop prescribing an ineffective treatment benefit.
In addition, if there was evidence concerning who benefited from compression hosiery,
treatment could be better targeted.
` This research is not likely to have an impact on national priorities.
Current The systematic review of the evidence identified 3 low or very low quality RCTs, two of
evidence base which were completed more than 15 years ago (see section 8.1). These investigated
patient assessed symptoms and adverse events but did not look at patients’ quality of
life. In addition, 5 observational studies were identified which provided some further
information. The GDG felt strongly that the nature of the evidence created much
uncertainty about the results for all relevant outcomes.
Equality Equality issues are not particularly relevant to this research question, although the ability
to put on and take off compression hosiery and whether that had an impact in the
adherence to the treatment strategy should be considered as part of the research
Feasibility The proposed research is considered by the GDG to be feasible and able to be carried out
within a realistic timescale and at an acceptable cost. There are no known ethical or
technical issues.
Other None
comments
Study design Randomised Controlled Trial

1 N.1.5 Compression after interventional treatment
2 What is the clinical and cost effectiveness of compression hosiery after interventional treatment for
3 varicose veins compared with no compression hosiery? If there is benefit, how long should
4 compression hosiery be worn for?
6 The benefit of compression after interventional treatment for varicose veins is unclear. A well
7 conducted multicentre randomised controlled trial (RCT) of compression hosiery after each of the
8 three main interventional treatments would help determine whether compression hosiery is
9 beneficial, and if so, what type of compression is best and how long it should be worn for. There
10 should be 6 RCT arms, one arm with compression and one arm without in each of three patient
11 groups: patients who have had endothermal ablation, patients who have had ultrasound-guided
12 foam sclerotherapy and patients who have had surgery. Each arm should have subgroups for
13 compression type and duration. Adherence to treatment with compression hosiery and the effect of
14 adherence on effectiveness should also be evaluated. A cost-effectiveness analysis should be
15 performed. If compression hosiery is beneficial, such a trial should help improve quality of life for
16 people with varicose veins and reduce the longer-term need for retreatment.

Importance to If the trial showed a benefit of compression hosiery after treatment this would lead to
patients or the altered guidance recommending compression after interventional treatment. This would
population improve patients’ quality of life.
Relevance to This research is of medium importance to the NICE guideline, as the research is relevant
NICE guidance to the recommendations in the guideline but the research recommendations are not key
to future updates.
Relevance to the The impact of this research on the NHS is minimal. If the research identified a benefit
NHS with compression after interventional treatment a change in recommendation would be
required which would lead to a change in practice in the NHS.
National This research is not relevant to any known national priority areas.
priorities
Current The evidence for this section was reviewed in chapter 10. Only 2 low / very low quality
evidence base randomised controlled trials were identified in this area which were both prone to
serious bias. In most cases the imprecision of the point estimate was too large to be able
to confidently judge the magnitude/direction of the true population effect.
Equality The research does not address equality issues as all people will be able to access the
intervention. Patient compliance with compression should be assessed in the research to
determine if there are any factors which meant that compression was not suitable for
specific groups.
Feasibility The research is expected to be able to be carried out within a realistic timescale and
acceptable cost. It is not expected that there would be any ethical or technical issues.
Other None
comments

Study design Randomised controlled trial

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National Clinical Guideline Centre

Varicose Veins Appendices

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Commissioned by the National Institute for

Varicose Veins Full Guideline Appendices - draft (January 2013)

Varicose Veins Full Guideline Appendices - draft (January 2013)

Varicose Veins Full Guideline Appendices - draft (January 2013)

Varicose Veins Full Guideline Appendices - draft (January 2013)

Varicose Veins Full Guideline Appendices - draft (January 2013)

Varicose Veins Full Guideline Appendices - draft (January 2013)

Varicose Veins Full Guideline Appendices - draft (January 2013)

Varicose Veins Full Guideline Appendices - draft (January 2013)

Varicose Veins Full Guideline Appendices - draft (January 2013)

Varicose Veins Full Guideline Appendices - draft (January 2013)

Varicose Veins Full Guideline Appendices - draft (January 2013)

1 Appendix B: Declarations of interest

Non-personal pecuniary (non-specific): The grant was awarded by an academic

Varicose Veins Full Guideline Appendices - draft (January 2013)

GDG meeting Declaration of Interests Action taken

Non personal pecuniary (non-specific): A The technique under investigation is not

Personal pecuniary (non-specific): Organised No direct sponsorship by any

Personal pecuniary (non-specific): Received a No direct sponsorship by any

Personal pecuniary (non-specific): Attended Pharmacological treatments are under

Personal non-pecuniary (non-specific): No direct sponsorship by any

Varicose Veins Full Guideline Appendices - draft (January 2013)

GDG meeting Declaration of Interests Action taken

1 B.2 Dr. Mustapha Azzam

Fourth GDG None None

Personal pecuniary (non-specific):Attended an First Sky Medical do not make anything

Varicose Veins Full Guideline Appendices - draft (January 2013)

GDG meeting Declaration of Interests Action taken

Ninth GDG No change to declarations of interest. None

Tenth GDG No change to declarations of interest. None

2 B.3 Professor Andrew Bradbury

Fifth GDG No change to declarations of interest. None

Varicose Veins Full Guideline Appendices - draft (January 2013)

GDG meeting Declaration of Interests Action taken

Sixth GDG Non-personal pecuniary (Specific): No personal knowledge of the

Ninth GDG No change to declarations of interest. None

Tenth GDG Did not attend this meeting None

2 B.4 Dr. Jocelyn Brookes

Varicose Veins Full Guideline Appendices - draft (January 2013)

GDG meeting Declaration of Interests Action taken

Fourth GDG Did not attend this meeting None

Fifth GDG None None

Sixth GDG Did not attend this meeting None

Seventh GDG None None

Eighth GDG None None

Ninth GDG Did not attend this meeting None

Tenth GDG None None

2 B.5 Mrs. Joyce Calam

Varicose Veins Full Guideline Appendices - draft (January 2013)

GDG meeting Declaration of Interests Action taken

Fourth GDG None None

Fifth GDG None None

Sixth GDG None None

Seventh GDG None None

Eighth GDG None None

2 B.6 Mr. David Evans

Varicose Veins Full Guideline Appendices - draft (January 2013)

GDG meeting Declaration of Interests Action taken

Fifth GDG No change to declarations of interest. None

Sixth GDG No change to declarations of interest. None