Graduated compression stockings for the initial treatment of varicose veins in people without venous ulceration 

Abstract

Background

Compression hosiery or stockings are often the first line of treatment for varicose veins in people without either healed or active venous ulceration. Evidence is required to determine whether the use of compression stockings can effectively manage and treat varicose veins in the early stages. This is the second update of a review first published in 2011.

Objectives

To assess the effectiveness of compression stockings for the only and initial treatment of varicose veins in people without healed or active venous ulceration.

Search methods

For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 12 May 2020. We also checked references of studies identified from the literature searches.

Selection criteria

We included randomised controlled trials (RCTs) involving people diagnosed with primary trunk varicose veins without healed or active venous ulceration (Clinical, Etiology, Anatomy, Pathophysiology (CEAP) classification C2 to C4). Included trials assessed compression stockings versus no treatment or placebo stockings, or compression stockings plus drug intervention versus drug intervention alone. We also included trials comparing different lengths and pressures of stockings. We excluded trials involving other types of treatment for varicose veins (either as a comparator to stockings or as an initial non‐randomised treatment), including sclerotherapy and surgery.

Data collection and analysis

We followed standard Cochrane methodology. Two review authors independently assessed trials for inclusion, extracted data, assessed risk of bias and assessed the certainty of the evidence using GRADE. Outcomes of interest were change in symptoms; physiological measures; complications; compliance; comfort, tolerance and acceptability of wearing stockings; and quality of life.

Main results

We included 13 studies with 1021 participants with varicose veins without healed or active venous ulceration. One study included pregnant women while other studies included participants who had sought medical intervention for their varicose veins by being on surgical waiting lists, or attending vascular surgery or dermatology clinics or outpatient departments. The stockings used in the studies exerted different levels of pressure, ranging from 10 mmHg to 50 mmHg. Five studies assessed compression stockings versus no compression stockings or placebo stockings. Three of these studies used knee‐length stockings, one used full‐length stockings and one used full tights. Eight studies compared different types or pressures of knee‐length stockings. The risk of bias of many included trials was unclear, mainly because of inadequate reporting. We were unable to pool studies as they did not report the same outcomes or used different ways to assess them. Many studies were small and there were differences in the populations studied. The certainty of the evidence was therefore low to very low.

Compression stockings compared with no treatment or placebo stockings

All four studies that reported change in symptoms found a subjective improvement by the end of the study. However, change in symptoms was not always analysed by comparing the randomised arms of the studies and was therefore subject to bias. Two studies assessed physiological measures using either ankle circumference or duplex sonography to measure oedema. Ankle circumference showed no clear difference between baseline and follow‐up while oedema was reduced in the stocking group compared with the placebo stocking group. Three studies reported complications or side effects with itching and irritation the main side effects reported. None of the trials reported severe side effects. Reports of compliance varied between studies. One study reported a high dropout rate with low levels of compliance due to discomfort, application and appearance; two studies reported generally good levels of compliance in the stocking group compared to placebo/no treatment. Two studies reported comfort, tolerance and acceptability with outcomes affected by the study population. Compression tights were increasingly rejected by pregnant women as their pregnancy progressed, while in one study of non‐pregnant women, the stockings group showed no more hindrance of normal activities and daytime discomfort when compared with placebo stockings. One study reported quality of life showing no clear differences between the stocking and placebo stocking groups.

Compression stockings compared with different compression stockings

All five studies that reported change in symptoms found a subjective improvement in symptoms by the end of the study. Change in symptoms was not always analysed comparing the randomised arms of the trials and was therefore subject to bias. Five studies reported a variety of physiological measures such as foot volumetry, volume reduction and change in diameter. Generally, there were no clear differences between study arms. Four studies reported complications or side effects, including sweating, itching, skin dryness, and constriction and tightness. None of the trials reported severe side effects. Two studies reported compliance showing no difference in compliance rates between stockings groups, although one study reported high initial levels of dropout due to discomfort, appearance, non‐effectiveness and irritation. Four studies reported comfort, tolerance and acceptability. Two studies reported similar levels of tolerance and discomfort between groups. Discomfort was the main reason for indicating a preference for one type of stocking over another. None of the studies assessed quality of life.

No conclusions regarding the optimum length or pressure of compression stockings could be made as there were no conclusive results from the included studies.

Authors' conclusions

There is insufficient high‐certainty evidence to determine whether or not compression stockings are effective as the sole and initial treatment of varicose veins in people without healed or active venous ulceration, or whether any type of stocking is superior to any other type. Future research should consist of large RCTs of participants with trunk varices either wearing or not wearing compression stockings to assess the efficacy of this intervention. If compression stockings are found to be beneficial, further studies assessing which length and pressure is the most efficacious could then take place.

Plain language summary

Wearing stockings to provide compression for the treatment of varicose veins

Review question

What is the effectiveness of compression stockings as the only and initial treatment of varicose veins in people without healed or active venous ulceration (leg ulcers)?

Background

Varicose veins are widened veins that twist and turn and are visible under the skin of the legs. They generally do not cause medical problems, although many people seek medical advice. Symptoms may include pain, ankle swelling, tired legs, restless legs, night cramps, heaviness, itching and distress from their cosmetic appearance. Complications such as oedema (build‐up of fluid), pigmentation, inflammation (swelling, redness and pain) and ulceration (sores) can also develop. Compression stockings are often the first line of treatment and come in a variety of lengths from knee‐length to full tights, and apply different pressures to support the flow of blood in the veins.

Study characteristics

We included 13 studies involving 1021 participants with varicose veins who had not experienced venous ulceration in this review (search run May 2020). Five studies assessed compression stocking versus no compression stocking (for example no treatment or placebo stocking with no graduated elastic). Three of these studies used knee‐length stockings, one used full‐length stockings and one used full tights. Eight studies compared different types or pressures of knee‐length stockings. The stockings used in the studies exerted different levels of pressure. One study included only pregnant women, while other studies included people who had sought medical intervention for their varicose veins by being on surgical waiting lists, or attending vascular surgery or dermatology (skin care) clinics or outpatient departments.

Key results

Participants considered their symptoms had improved when stockings were worn in the nine studies that assessed this outcome, but these assessments were not always made by comparing one treatment group of the trial with a control group in the same study and was therefore subject to bias.

Two studies comparing stockings with placebo stockings measured physical signs; there was no clear difference between baseline and follow‐up for ankle circumference, while oedema was reduced in the stocking group compared with the placebo stocking group. Generally there were no clear differences between studies comparing two types of stockings for volume reduction and change in diameter (ways to measure oedema).

Complications or side effects ranged from sweating, itching, irritation, skin dryness and a feeling of tightness. There were no severe or long‐lasting side effects.

Two studies comparing stockings with different stockings, and four studies comparing stockings with placebo/no treatment assessed compliance (whether the person used the stockings as directed). In the stocking versus different stocking studies, there was no clear difference between the stockings, with generally low levels of compliance reported. In the stocking versus placebo/no treatment group, three studies reported results. Of these, one study reported a high initial dropout rate with generally low levels of compliance. The other two studies reported generally good compliance in the stocking group. Some reasons provided for non‐compliance included discomfort, difficulty in putting the stockings on, appearance, not being effective and causing irritation.

Four studies that compared stockings with different stockings and two studies that compared stockings with placebo/no treatment assessed comfort, tolerance and acceptability of stockings. Comparing stockings with placebo/no treatment, comfort, tolerance and acceptability was affected by the study population. Compression tights were increasingly rejected by pregnant women as their pregnancy progressed, while in a study of non‐pregnant women, the stockings group showed no more hindrance of normal activities and daytime discomfort when compared with placebo stockings. In the stocking versus different stockings studies, two studies reported similar levels of tolerance and discomfort between the types of stocking. Discomfort was the main reason for indicating a preference for one type of stocking over another.

One study assessed quality of life, showing no clear differences between the stocking and no stocking groups.

No conclusions regarding the optimum length or pressure of compression stockings could be made as there were no conclusive results from the included studies. 

Certainty of the evidence

The certainty of the evidence was low or very low because of risk of bias due to poor reporting, not all studies assessed the same outcomes, they assessed them in different ways, or reported them in a way that they could be combined and analysed with other studies. Evidence from available trials is not sufficient to determine if compression stockings as the only and initial treatment are effective in managing and treating varicose veins in the early stages.

Summary of findings

Summary of findings 1. Compression stockings compared with no treatment or placebo stockings for the initial treatment of varicose veins without venous ulceration.

Compression stockings compared with no treatment or placebo stockings for the initial treatment of varicose veins without venous ulceration
Patient or population: people with varicose veins without venous ulceration Settings: outpatient clinics Intervention: compression stockings Comparison: no treatment or placebo stockings
Outcomes	Anticipated absolute effects*		Relative effect	No of participants (RCTs)	Certainty of the evidence (GRADE)	Comments
	Risk with no treatment or placebo stockings	Risk with compression stockings
Change in symptoms (ranging from 1 week to 3 months)	See comments		See comments	232 (4 RCTs)	⊕⊕⊝⊝ Lowa	Unable to pool studies because of differences in the way change in symptoms assessed and reported.
Physiological measures (1 week)	See comments		See comments	90 (2 RCTs)	⊕⊝⊝⊝ Very lowb	Unable to pool studies due to the different physiological measures assessed.
Complications (1 week, 4 weeks and up to 6 weeks' postpartumc)	See comments		See comments	148 (3 RCTs)	⊕⊝⊝⊝ Very lowd	All 3 studies reported on complications by reporting side effects. Unable to pool studies due to the differences in the way complications reported.
Compliance (1 week and up to 6 weeks' postpartumc)	See comments		See comments	136 (3 RCTs)	⊕⊕⊝⊝ Lowe	Unable to pool studies because of the differences in compliance assessments and study populations.
Comfort, tolerance and acceptability of wearing stockings (1 week and up to 6 weeks' postpartumc)	See comments		See comments	106 (2 RCTs)	⊕⊝⊝⊝ Very lowf	Unable to pool studies because of differences in assessments of comfort and tolerance between the studies.
Quality of life (3 months)	See comments		See comments	70 (1 RCT)	⊕⊕⊝⊝ Lowg	Single study assessed quality of working life using the AVVQ.
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). AVVQ: Aberdeen Varicose Veins Questionnaire; RCT: randomised controlled trial.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

^aDowngraded two levels for risk of bias (one study at high risk of bias for blinding and one study at unclear risk of bias) and inconsistency (differences in the way change in symptoms assessed and reported).
^bDowngraded three levels for risk of bias (one study at unclear risk of bias), inconsistency (different physiological measures assessed), indirectness (physiological measures are surrogate measures) and imprecision (two small studies).
^cOne study did not clearly report the duration of the study (Coughlin 2001): quote: "Questionnaires and assessment of women performed at booking, 34 weeks and 6 weeks post partum." No information as to whether women were instructed to stop wearing the stockings six weeks' postpartum or just stopped of their own accord.
^dDowngraded three levels for risk of bias (two studies at unclear risk of bias), inconsistency (differences in the way complications were reported), and imprecision (small studies reporting few events).
^eDowngraded two levels for risk of bias (one study at unclear risk of bias) and inconsistency (compliance in study with pregnant women very different from other two studies).
^fDowngraded three levels for risk of bias (one study at unclear risk of bias), inconsistency (different populations and different ways of assessing comfort), and imprecision (two small studies)
^gDowngraded two levels for risk of bias (study at high risk of bias for blinding) and imprecision (one study, small number of participants).

Summary of findings 2. Compression stockings compared with compression stockings for the initial treatment of varicose veins without venous ulceration.

Compression stockings compared with compression stockings for the initial treatment of varicose veins without venous ulceration
Patient or population: people with varicose veins without venous ulceration Settings: outpatient clinics Intervention: one type or pressure of compression stocking Comparison: another type or pressure of compression stockings
Outcomes	Anticipated absolute effects*		Relative effect	No of participants (RCT)	Certainty of the evidence (GRADE)	Comments
	Risk with another type or pressure of compression stockings	Risk with one type or pressure of compression stockings
Change in symptoms (ranging from 3 weeks to 6 months)	See comments		See comments	616 (5 RCTs)	⊕⊕⊝⊝ Lowa	Unable to pool studies due to the various symptoms and assessments used to assess change in symptoms.
Physiological measures (ranging from 15 minutes to 8 weeks)	See comments		See comments	141 (5 RCTs)	⊕⊝⊝⊝ Very lowb	Unable to pool studies due to the differences in the way physiological measures assessed.
Complications (ranging from 15 minutes to 6 months)	See comments		See comments	541 (4 RCTs)	⊕⊕⊝⊝ Lowc	1 study reported on complications while a further 3 studies reported on side effects. Unable to pool studies because of the differences in the way complications reported.
Compliance (ranging from 6 weeks to 6 months)	See comments		See comments	467 (2 RCTs)	⊕⊕⊝⊝ Lowd	Unable to pool studies because of the differences in compliance assessments between the studies.
Comfort, tolerance and acceptability of wearing stockings (ranging from 3 weeks to 6 months)	See comments		See comments	578 (4 RCTs)	⊕⊝⊝⊝ Very lowe	Unable to pool studies because of differences in assessments of comfort and tolerance between the studies.
Quality of life	See comments		See comments	See comments	See comments	None of the included studies assessed quality of life using a standard questionnaire.
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). RCT: randomised controlled trial.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

^aDowngraded two levels for risk of bias (three studies at unclear risk of bias) and inconsistency (variety of symptoms and assessments used to assess change in symptoms).
^bDowngraded three levels for risk of bias (one study at high risk of bias and three studies at unclear risk of bias), inconsistency (variety pf physiological measures assessed and duration of wearing stockings), indirectness (physiological measures are surrogate outcomes) and imprecision (small studies).
^cDowngraded two levels for risk of bias (two studies at unclear risk of bias) and inconsistency (different types of stockings and duration of wearing stockings).
^dDowngraded two levels for risk of bias (one study at unclear risk of bias) and indirectness (different way of assessing compliance as studies use either self‐reporting or random visits).
^eDowngraded three levels for risk of bias (two studies at unclear risk of bias), inconsistency (different types of stockings and duration of wearing stockings) and indirectness (different ways to assess comfort and tolerance).

Background

Description of the condition

Varicose veins are tortuous, widened veins in the subcutaneous tissue of the lower limb (Campbell 2006). Varicose veins that have arisen as a result of a known cause, such as a previous deep vein thrombosis (DVT), are known as secondary varicose veins (Golledge 2003). Theories on the cause of primary varicose veins range from initial structural weakness within the vein wall, which leads to vein dilation, to valve incompetence leading to pooling of the blood and vein dilation (Golledge 2003; London 2000). The Clinical, Etiology, Anatomy, Pathophysiology (CEAP) classification for chronic venous disorders was developed in 1994 by the American Venous Forum and was revised and disseminated in 2004 (Eklöf 2004). It serves as a systematic guide to the diagnosis and classification of chronic venous disorders, which was previously lacking. Today, most published papers on chronic venous disorders will use all or some of the CEAP classification (Eklöf 2004). There are six categories, ranging from small superficial thread‐like veins (C1) to active venous ulcers (C6). A classification of C0 is given where no clinical findings of venous disease are found. Therefore, CEAP classification is used to classify and diagnose varicose veins, which if uncomplicated are classed as grade C2. A classification of C3 indicates varicose veins with oedema and a classification of C4 indicates varicose veins with skin changes due to venous disorders (Padberg 2005). In 2004, it was also decided to define a varicose vein as greater than 3 mm in diameter, to differentiate from reticular veins (Eklöf 2004).

Although varicose veins are associated with low morbidity and mortality, many people seek medical advice and there is some evidence that quality of life (QoL) can be improved following treatment. Approximately 2% of National Health Service (NHS) resources in the UK are spent on managing venous disease, with an estimated GBP 20 million to GBP 25 million (excluding non‐hospital costs) spent on operations for varicose veins in the year 2001 (Beale 2005). More recently, NICE 2013 concluded that because there is currently little evidence to demonstrate the benefits of compression stockings for symptom relief or improved QoL, it is not possible to calculate the cost‐effectiveness of compression hosiery.

Many people with varicose veins are asymptomatic, but some experience aching, dullness in the lower limbs, itching, throbbing, distress about the cosmetic appearance and swelling (Metcalfe 2008). Around 5% will develop complications including haemorrhage, thrombophlebitis, oedema, skin pigmentation, atrophie blanche, varicose eczema, lipodermatosclerosis and ulceration (Beale 2005). NICE 2013 estimate that 3% to 6% of people who have varicose veins in their lifetime will develop venous ulcers.

Prevalence of the condition varies widely between studies from different countries (up to 56% in men and 60% in women) and few studies have measured the incidence within the general population (Robertson 2008). NICE 2013 reported that in the UK visible varicose veins in the lower limb are estimated to affect at least a third of the population.

Wittens 2015 reported that the prevalence of varicose veins (CEAP C2) is variable with reported incidence ranging from 20% to 64%. Although there is no obvious gender difference in prevalence, age and increased body mass index appear to be important risk factors for developing varicose veins. Historically, there has been more data from countries in the western world. However, more recent evidence has shown that the incidence of varicose veins (CEAP C2) is significantly lower in the Middle East (Rabe 2012; Wittens 2015).

Description of the intervention

Lower limb compression has been used to treat varicose veins since biblical times (Pierson 1983). Compression hosiery or stockings (knee and thigh length and full tights) are widely used in the first‐line treatment of varicose veins (NICE 2013). Although compression may be achieved by different modalities, this Cochrane Review is restricted to compression stockings. Stockings come in a variety of lengths (knee‐, thigh‐ or full‐length, and full tights) and compression strength or pressures. The British and European Standards for classifying compression pressure or strengths differ.  For example, for class 1, the British Standard pressure can be between 14 mmHg and 17 mmHg whereas the European standard pressure can be between 18 mmHg and 21 mmHg. The most frequently prescribed graduated compression stocking is the European Standard Class II, exerting pressure between 23 mmHg and 32 mmHg (NICE 2013). The optimum lengths and pressures are not known, but studies suggest that a compression pressure between 20 mmHg and 30 mmHg is tolerated better than higher levels (Beale 2005).

How the intervention might work

Optimum management of varicose veins requires accurate diagnosis and identification of the source of venous incompetence, and treatment should aim to abolish venous reflux and relieve symptoms (Beale 2005). Graduated compression works by applying a controlled pressure to the skin. This supports the superficial venous system by exerting an external pressure that is greatest at the ankle (minimum of 14 mmHg) and decreases up the leg (Johnson 2002). By reducing venous capacity and increasing venous velocity in the deeper veins, venous stasis and reflux are reduced helping to reduce the severity of varicose veins and the associated symptoms (Walker 2007). However, it is important to be aware that the effect of compression stockings is influenced by many factors. For example, the material (both compression class and elasticity) of the stocking, the size and shape of the leg, and the activity of the wearer can all influence the compression applied (Rabe 2008).

Why it is important to do this review

In 2013 the National Institute for Health and Care Excellence (NICE) guidelines on varicose veins reported, "There is … no established framework within the NHS for the diagnosis and management of varicose veins. This has resulted in wide regional variations in the management of varicose veins in the UK" (NICE 2013). A first‐line method to the management of varicose veins is the use of compression therapy, such as the application of compression stockings. Although compression therapy is widely used in the management of varicose veins, there is still conflicting, poor‐quality evidence on its effectiveness. There is evidence that people with varicose veins without healed or active venous ulceration can develop severe complications and consume a large amount of NHS resources (Atkins 2020). If treatments such as compression stockings can be used to treat varicose veins in the early stages, morbidity and resource use may ultimately be reduced. In this review, we assessed the effectiveness of compression stockings for the initial treatment of varicose veins in people without healed or active venous ulceration, including the optimum length and pressure of stockings and whether the use of stockings has any effect on the symptoms related to varicose veins.

Objectives

To assess the effectiveness of compression stockings for the only and initial treatment of varicose veins in people without healed or active venous ulceration.

Methods

Criteria for considering studies for this review

Types of studies

We considered all randomised controlled trials (RCTs) in people with varicose veins and without healed or active venous ulceration (CEAP C2 to C4) that assessed:

• compression stockings versus no treatment;

• compression stockings versus placebo compression stocking (PS; Tubigrip, for example, which does not provide graduated pressure); or

• compression plus a drug intervention versus the drug intervention alone.

We also included studies that compared different lengths and pressures of compression stockings. We included parallel group and cross‐over trials. There were no language restrictions.

We excluded trials that compared compression stockings with interventions other than no treatment, placebo compression stockings or stockings of another length or pressure (e.g. sclerotherapy, surgery, laser therapy, exercise, balneotherapy or hydrotherapy).

Existing Cochrane Reviews have assessed the treatment of varicose veins using surgical techniques including sclerotherapy (Rigby 2004; Tisi 2006), as well as assessing the best form of prevention and management of venous disease in certain subsets of the population such as pregnant women (Smyth 2015) and those travelling by air (Clarke 2021).

We excluded trials that compared compression stockings against no treatment or a placebo stocking (PS) as an adjuvant to primary (initial) treatment with surgery, sclerotherapy or laser therapy, and those assessing other methods of compression such as pneumatic compression techniques.

We excluded studies of participants with CEAP C5 or C6, which indicates venous ulcers, as this is a more severe form of venous disease.

Types of participants

We included adults (aged 18 years and above) of both sexes who experienced varicose veins without having healed or active venous ulceration in the lower limb(s). The classification of varicose veins was performed according to CEAP. If methods such as duplex scanning were used to assist in the diagnosis, a clinical diagnosis of trunk or stem varicose veins (CEAP C2) was also required, with or without ankle oedema or minor skin changes (CEAP C3 and C4). Where venous leg ulcers (CEAP C5 and C6) or other severe complications were present, the participants were not included. In studies where the CEAP classification was not used, in early studies for example, a diagnosis by a clinician of trunk varices or varicose veins was sufficient.

Comorbidity or pregnancy did not influence the decision to include or exclude a trial. Trials including participants who had bilateral varicose veins but where compression was only applied unilaterally were included.

Types of interventions

Interventions included compression from any type of hosiery that exerted a graduated pressure on the lower limb(s). We included any length (knee, thigh, full tights) and grade of pressure. Compression had to be from a graduated pressure stocking and not from a more general support bandage such as Tubigrip.

We compared the intervention with no intervention, a PS such as Tubigrip, or both.

We also included trials that involved participants taking a drug intervention when the drug alone was compared against drug plus compression stocking, allowing the effect of the compression stocking to be assessed.

We assessed comparisons between different lengths or different grades of pressure, or both, where trials compared stockings in two arms of the same trial.

Types of outcome measures

Primary outcomes

• Change in symptoms: such as aching and itching, reported by participants.

• Physiological measures used to monitor the impact of the intervention on varicose vein status: such as venous pressure at the ankle.

Secondary outcomes

• Complications: these included direct complications or side effects from wearing the stockings, for example, itching and increase in temperature.

• Compliance: this included ensuring the participant was wearing the stockings and that they were being worn correctly, measured subjectively (e.g. a report from the participant that they had stopped wearing the stockings).

• Comfort, tolerance and acceptability of wearing stockings.

• Quality of life: where this was measured using a validated standard questionnaire such as Aberdeen Varicose Veins Questionnaire (AVVQ) or Short‐Form 36 (SF‐36).

Search methods for identification of studies

Electronic searches

For this update, the Cochrane Vascular Information Specialist conducted systematic searches of the following databases for RCTs without language, publication year or publication status restrictions.

• Cochrane Vascular Specialised Register via the Cochrane Register of Studies (CRS‐Web searched on 12 May 2020).

• Cochrane Central Register of Controlled Trials (CENTRAL) Cochrane Register of Studies Online (CRSO 2020, Issue 4).

• MEDLINE (Ovid MEDLINE Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE) (searched from 1 January 2017 to 12 May 2020).

• Embase Ovid (searched from 1 January 2017 to 12 May 2020).

• CINAHL EBSCO (searched from 1 January 2017 to 12 May 2020).

• AMED Ovid (searched from 1 January 2017 to 12 May 2020).

The Information Specialist modelled search strategies for databases on the search strategy designed for CENTRAL. Where appropriate, they were combined with adaptations of the highly sensitive search strategy designed by Cochrane for identifying RCTs and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions Chapter 6, Lefebvre 2011). Search strategies for major databases are provided in Appendix 1.

The Information Specialist searched the following trials registries on 12 May 2020.

• World Health Organization International Clinical Trials Registry Platform (who.int/trialsearch).

• ClinicalTrials.gov (clinicaltrials.gov).

Searching other resources

We checked reference lists of studies identified from the literature searches and contacted journal article authors in order to clarify information where needed.

Data collection and analysis

Selection of studies

We used the search strategies described to obtain titles and abstracts of studies that were potentially relevant to this review. We used Covidence software for the screening and study selection process (Covidence). Two review authors (SK and MS) independently screened the titles and abstracts to identify studies and select trials for possible inclusion in the review. We obtained full‐text articles where studies met the above inclusion criteria and two review authors (SK and MS) independently reviewed them. We resolved any disagreements by discussion.

Where studies had multiple publications, we collated the reports of the same study so that each study, rather than each report, was the unit of interest for the review, and such studies had a single identifier with multiple references.

Data extraction and management

For this update, two review authors (SK and MS) independently reviewed, extracted and summarised information from the studies using standardised data extraction forms specific to Cochrane Vascular.

We collected the following information:

• methods (study design, method of randomisation, concealment of allocation, blinding, power calculations, and source of funding);

• participants (number, age, sex, inclusion and exclusion criteria);

• interventions (treatment, control or placebo, duration);

• outcomes (primary and secondary).

We used Review Manager Web for the production of this review (RevMan Web 2021).

Assessment of risk of bias in included studies

We completed risk of bias tables for each included study along with narrative in the text to assess the methodological quality of the included studies. Two review authors (SK and MS) independently completed risk of bias tables in accordance with the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We resolved any disagreements by discussion. The minimum level of study quality included in this review was an RCT. Where this level of quality was not met, the trials were excluded. If enough high‐quality studies were found, we planned sensitivity analyses.

The risk of bias tables included six domains: adequate sequence generation, allocation concealment, blinding of personnel and participants and outcome assessors, incomplete outcome data addressed, free of selective reporting and free of other bias. Two review authors (SK and MS) independently gave a judgement of low risk of bias, high risk of bias or unclear risk of bias for each domain, along with a description as to why the judgement was made.

Measures of treatment effect

In line with the Cochrane Handbook for Systematic Reviews of Interventions, for dichotomous outcomes, we planned to express results as risk ratio (RR) with 95% confidence interval (CI). For continuous scales of measurement, we planned to use mean difference (MD) if studies used the same scales, or the standardised mean difference (SMD) if they used different scales (Higgins 2011). If meta‐analysis was not appropriate, we presented the results narratively.

Unit of analysis issues

We included all types of RCTs. In the case of a cross‐over trial, we included data from all periods. The participants were the unit of analysis.

Dealing with missing data

Where data were missing or unclear, we attempted to contact the study author to obtain the information. Where we were unable to obtain missing data, we used assumptions such as assuming normal distribution to use the median value as a mean value (Higgins 2011). We described any assumptions made with the relevant analysis.

Assessment of heterogeneity

We considered clinical heterogeneity regarding the participants, interventions and outcomes. We planned to assess heterogeneity between trials using the Chi² test and the I² statistic if meta‐analysis was appropriate.

Assessment of reporting biases

Where applicable, we planned to assess publication bias via a funnel plot of outcomes. These can show publication bias by an asymmetrical output (Higgins 2011). Ultimately, a funnel plot was not carried out in this review due to the small number of studies included in the statistical analysis.

Data synthesis

We planned meta‐analyses where appropriate data were available. Ultimately, we did not perform meta‐analyses due to the lack of compatible data from the different studies. If meta‐analyses had been completed, many assumptions would have had to be made due to the poor levels of reporting.

Subgroup analysis and investigation of heterogeneity

No subgroup analyses were preplanned.

Sensitivity analysis

If sufficient high‐quality trials had been available, we planned sensitivity analysis to determine the robustness of the review findings.

Summary of findings and assessment of the certainty of the evidence

In this review, we only included RCTs. We used GRADEpro GDT to help us create summary of findings tables (GRADEpro GDT). We reported the following outcomes in the summary of findings tables: change in symptoms, physiological measures, complications, compliance and QoL. We downgraded the evidence from 'high certainty' by one or two levels for serious or very serious study limitations (risk of bias), indirectness and inconsistency of evidence, imprecision of effect estimates or potential publication bias according to the Cochrane Handbook for Systematic Reviews (Higgins 2011) and Atkins 2004.

Results

Description of studies

Results of the search

See Figure 1.

1.

Study flow diagram. CEAP: Clinical, Etiology, Anatomy, Pathophysiology; RCT: randomised controlled trial.

The search identified 1720 records. After removing duplicates we screened the titles and abstracts of 1110 records and assessed 1015 of them as not relevant. We obtained and read the full text of 95 articles and excluded 36 studies (43 records) with reasons (see Characteristics of excluded studies table). We included six new studies resulting in 13 studies (18 reports) contributing to the updated review (see Characteristics of included studies table).

For this update, we identified six new studies for inclusion (Cazaubon 2013; Couzan 2012; Heidarimoghadam 2020; Kakkos 2018; Mariani 2013; Riebe 2018), 36 additional studies for exclusion (Adamzcyk 2013; Al Shammeri 2014; Arnoldi 1976; Benigni 2013; Blazek 2013; Buhs 1999; Chant 1979; Couzan 2009; Diamand 2012; Diehm 1996; DRKS00008829; DRKS00012258; DRKS00014743; Fentem 1976; Genzel 1991; Gronbaek 1991; Häfner 2000; Häfner 2001; Jeanneret 2014; Labropoulos 1994; Lattimer 2017; Lord 2004; Moehrle 2007; Mosti 2010; Mosti 2012; Muller‐Buhl 1998; NCT01793194; Park 2013; Pohlmann 1997; Raj 1981; Saliba 2020; Vayssairat 2000; Weiss 1999a; Westphal 2019; Wolff 2011; Zajkowski 2002), and five new ongoing studies (DRKS00012259; NCT01402921; NCT03429959; NCT03743597; RBR‐5n9cmf; see Characteristics of ongoing studies table).

Included studies

See the Characteristics of included studies table.

We included 13 studies (18 reports) (Anderson 1990; Cazaubon 2013; Chant 1985; Chant 1989; Chauveau 2000; Coughlin 2001; Couzan 2012; Heidarimoghadam 2020; Jones 1980; Jungbeck 1997; Kakkos 2018; Mariani 2013; Riebe 2018). The studies were published between 1980 and 2020 and involved 1021 participants with varicose veins without healed or active venous ulceration. All but one of the studies were set in Europe: five studies were set in the UK (Anderson 1990; Chant 1985; Chant 1989; Coughlin 2001; Jones 1980), three in France (Cazaubon 2013; Chauveau 2000; Couzan 2012), one in Sweden (Jungbeck 1997), one in Greece (Kakkos 2018), one in Italy (Mariani 2013), and one in Germany (Riebe 2018). One study was set in Iran (Heidarimoghadam 2020). All included studies were RCTs but five had a cross‐over design (Anderson 1990; Cazaubon 2013; Coughlin 2001; Jones 1980; Riebe 2018).

Participants

All participants were diagnosed with primary varicose veins without healed or active venous ulceration as specified in the inclusion criteria. Many studies did not use the CEAP classification; mostly this was because they were conducted prior to the development of the classification. The studies varied in the amount of detail provided to describe their exclusion and inclusion criteria.

In 11 studies, all participants had varicose veins and were randomised into different groups, either to compare types of stocking or different pressures, or to compare wearing stockings versus not wearing stockings (Anderson 1990; Cazaubon 2013; Chant 1985; Chant 1989; Chauveau 2000; Coughlin 2001; Couzan 2012; Heidarimoghadam 2020; Jungbeck 1997; Kakkos 2018; Mariani 2013). Two studies included other groups of participants who were not diagnosed with varicose veins (Jones 1980; Riebe 2018). These trials clearly distinguished subgroups at entry and in the results, so those participants with varicose veins could be identified for inclusion in our analyses.

Four studies recruited people from surgical waiting lists (Anderson 1990; Chant 1985; Chant 1989; Jones 1980), five from outpatient departments (Cazaubon 2013; Chauveau 2000; Couzan 2012; Jungbeck 1997; Kakkos 2018), one from a vascular surgery clinic (Mariani 2013), one from a dermatology clinic (Riebe 2018), and one from a maternity setting as participants were pregnant (Coughlin 2001). Heidarimoghadam 2020 included female hairdressers. All included participants were outpatients.

Eight studies included both men and women (Anderson 1990; Cazaubon 2013; Couzan 2012; Jones 1980; Jungbeck 1997; Kakkos 2018; Mariani 2013; Riebe 2018). Three studies included only females (Chauveau 2000; Coughlin 2001; Heidarimoghadam 2020), one because the study included pregnant women only (Coughlin 2001). Two studies did not report the gender of participants (Chant 1985; Chant 1989). Six studies stated the numbers of male and female participants (Cazaubon 2013; Couzan 2012; Jones 1980; Kakkos 2018; Mariani 2013; Riebe 2018), with the others stating that randomised groups were evenly matched for sex. In the studies where the participants' sex was stated, there were more women than men, possibly reflecting a greater prevalence of symptomatic varicose veins in women, or that women seek medical help for varicose veins more readily than men.

The age range also varied between studies. Some studies did not specify age (Chant 1985; Chant 1989; Coughlin 2001; Jones 1980), and in the others the age ranged from 20 to 82 years (Anderson 1990; Cazaubon 2013; Chauveau 2000; Couzan 2012; Heidarimoghadam 2020; Jungbeck 1997; Kakkos 2018; Mariani 2013; Riebe 2018).

Interventions

Eleven studies used knee‐length graduated compression stockings (Cazaubon 2013; Chant 1985; Chant 1989; Chauveau 2000; Couzan 2012; Heidarimoghadam 2020; Jones 1980; Jungbeck 1997; Kakkos 2018; Mariani 2013; Riebe 2018). Coughlin 2001 used compression tights and Anderson 1990 used full‐length stockings. 

Four studies randomised participants to wear one type of compression stocking and compared with either no stocking or PS (Coughlin 2001; Heidarimoghadam 2020; Kakkos 2018; Mariani 2013). Anderson 1990 assessed the effect of compression stockings and oxerutins (Paroven), alone and in combination, and the groups were identifiable for analyses. The remaining eight studies assessed one type or pressure of stocking against another (Cazaubon 2013; Chant 1985; Chant 1989; Chauveau 2000; Couzan 2012; Jones 1980; Jungbeck 1997; Riebe 2018).

The studies used following compression stockings or tights: class 1 compression tights (Coughlin 2001); full length hosiery giving a pressure of 30 mmHg to 40 mm Hg at the ankle (Anderson 1990); Sigvaris stockings giving a pressure of 30 mmHg to 40 mmHg at the ankle or 40 mmHg to 50 mmHg at the ankle (Chant 1985); an Eesiness NHS two‐way stocking (20 mmHg at the ankle) and Sigvaris medium stocking (30 mmHg to 40 mmHg at the ankle) (Jones 1980); French class 1 (10 mmHg to 15 mmHg) and French class 2 (15 mmHg to 20 mmHg) below‐knee stockings (Chauveau 2000); Jobst Medical Leg wear knee‐hi class 1 (20 mmHg at the ankle) and Jobst Medical Leg wear knee‐hi class 2 (30 mmHg at the ankle) (Jungbeck 1997); Sigvaris and Medi Plus support hose (Chant 1989); progressive compression stocking (Progressive N'System) and degressive compression stocking (Class III Veinostim) (Cazaubon 2013); upward progressive compressive stockings (10 mmHg at the ankle, 23 mmHg at the upper calf) and degressive compressive stockings (30 mmHg at the ankle, 21 mmHg at the upper calf) (Couzan 2012); graduated elastic stockings VARISAN TOP, Class 1 (18 mmHg to 21 mmHg at the ankle) and VARISAN diabetic (0 mmHg at the ankle) (Kakkos 2018); class II medical compression stockings (MCS; BSN medical, 23 mmHg to 32 mmHg at ankle) and PS with 3 mmHg to 6 mmHg at ankle (Mariani 2013); and graduated elastic compression stockings (GECS; compression class II, 23 mmHg to 32 mmHg, maximal interface pressure exerted at ankle with a declining pressure from distal to proximal) and progressive elastic compression stockings (PECS; maximal interface pressure (23 mmHg to 32 mmHg) over the maximal calf circumference) (Riebe 2018). Heidarimoghadam 2020 used compression stockings that covered feet and lower legs (ADOR, Faraz Gostar Farham co, Iran).

Due to the variety of stockings and pressures used it was difficult to make comparisons between stockings or study results.

Outcomes

Most studies assessed more than one prespecified outcome of this review.

Nine studies used the change in symptoms as an outcome measure (Anderson 1990; Chant 1985; Couzan 2012; Heidarimoghadam 2020; Jones 1980; Jungbeck 1997; Kakkos 2018; Mariani 2013; Riebe 2018).

Three of these used a visual analogue scale (VAS) to determine change in symptoms before and after wearing stockings (Anderson 1990; Jungbeck 1997; Kakkos 2018). Anderson 1990 and Kakkos 2018 reported the results of the VAS at the level of individual symptoms. Jungbeck 1997 grouped all symptoms together and reported the results before and after intervention for the two different classes of stocking used in the trial.

Chant 1985 and Jones 1980 used self‐reporting of symptoms as their outcome measure. Although Jones 1980 reported symptoms, it was not the study's primary outcome and they reported no data. Chant 1985 stated the number of participants in each stocking group who reported an improvement in symptoms, as well as the number of participants who were removed from the surgical waiting list. Couzan 2012 used a combination of two, four‐level scores, with the following categories: disappearance, important amelioration, slight amelioration and lack of amelioration, to assess improvement of pain and heavy legs without the onset of either ulcer, DVT or superficial vein thrombosis (SVT) of the lower limb, or pulmonary embolism (PE).

Riebe 2018 used the Venous Clinical Severity Score (VCSS) to report severity of symptoms and course of the disease while Couzan 2012 and Kakkos 2018 used a modified VCSS that did not account for the attribute of compression. Mariani 2013 reported patient mobility. Heidarimoghadam 2020 reported pain and fatigue using the Chronic Pain Grade Scale (CPGS) and the Muscle Fatigue Questionnaire in Lower Extremities (MFQ).

Seven studies reported the change in physiological measures (Cazaubon 2013; Chauveau 2000; Jones 1980; Jungbeck 1997; Kakkos 2018; Mariani 2013; Riebe 2018). Jungbeck 1997 and Jones 1980 used foot volumetry before and after wearing stockings. Chauveau 2000 investigated calf volume changes, while Riebe 2018 assessed volume reduction (oedema reduction) of two sections of the lower limb, and Kakkos 2018 studied ankle circumference. Mariani 2013 assessed reduction of oedema using duplex sonography, and Cazaubon 2013 investigated change in diameter of deep and superficial veins, change in venous reflux and pressure of stockings while in use. Couzan 2012 performed a physical examination and evaluated CEAP.

The only study to assess complications of wearing compression stockings as their main outcome was Chauveau 2000. This study determined whether below‐knee stockings (class 1 (10 mmHg to 15 mmHg) and class 2 (15 mmHg to 20 mmHg)) impeded venous return by a tourniquet effect using air plethysmography with venous occlusion. Anderson 1990 described side effects of headache, abdominal pain and nausea, which occurred throughout the trial, but these could have been caused by the other interventions that were given, which included oxerutins and a placebo tablet. Couzan 2012 reported comfort and harm of stockings and Riebe 2018 reported side effects. No trials reported severe side effects.

Five studies assessed compliance (Anderson 1990; Chant 1989; Coughlin 2001; Couzan 2012; Kakkos 2018). Coughlin 2001 investigated the acceptability, compliance and usage of compression tights in pregnant women at various time points up to six weeks' postpartum via participant self‐report. Chant 1989 assessed compliance of two different types of stocking (Sigvaris and Medi Plus) by prescribing participants the stockings and then visiting them at home on a random basis, on average six weeks later, to determine whether or not they were wearing the stockings. The study also recorded the reasons why participants did not wear stockings; one of these being "caused irritation." Anderson 1990 assessed self‐reported measures of how long the participants wore stockings every day. Kakkos 2018 monitored compliance using log sheets on which participants entered the hours they had used their stockings every day while Couzan 2012 interviewed participants concerning compliance.

Five studies reported comfort, tolerance and acceptability of wearing stockings (Chant 1985; Coughlin 2001; Jones 1980; Mariani 2013; Riebe 2018). Three studies assessed the difficulty of donning the stockings or ease of application (Cazaubon 2013; Chant 1989; Couzan 2012).

Heidarimoghadam 2020 assessed QoL, using the AVVQ.

Length of studies

Studies varied in length from one day (wearing each of the two types of stocking for 15 minutes) (Chauveau 2000) to throughout pregnancy and up to six weeks' postpartum (Coughlin 2001). For most studies, it was difficult to determine for how long participants actually wore the stockings, and in this review, we used the time period taken when the assessors reviewed participants. However, this relied on the participants actually wearing the stockings between assessments.

Funding sources and acknowledgements

Anderson 1990 acknowledged Zyma (UK) Ltd and Ganzoni (Switzerland) for providing oxerutins and placebo capsules and Sigvaris 503 graduated compression hosiery. Chant 1985 reported that Sigvaris Company provided the stockings for their study. Jones 1980 acknowledged Ganzoni and Cie AG, St Gallen, Switzerland for supplying the Sigvaris stockings and reported that their study was supported by a Medical Research Council grant. Jungbeck 1997 acknowledged Beiersdorf AG, Germany for the supply of stockings and the contribution to the work. Kakkos 2018 reported that their study was partially funded by VICAN‐ N. Anagnostakis S.A, Athens, Greece. The funder provided the two types of stockings with no other involvement in the study. Riebe 2018 reported that Bauerfeind (Zeulenroda, Germany) provided the compression stockings. Cazaubon 2013 did not specifically report funding but reported that randomisation was carried out on behalf of Pierre Fabre Laboratories (France) and one author was a staff member of Pierre Fabre Laboratories; and Couzan 2012 reported that Pierre Fabre Laboratories approved the study protocol, provided the stockings, gave an unrestricted grant for the conduct of the study and was given the opportunity to comment on the manuscript. Five studies did not report or acknowledge funding sources (Chant 1989; Chauveau 2000; Coughlin 2001; Heidarimoghadam 2020; Mariani 2013).

Excluded studies

See Characteristics of excluded studies table.

For this update, we excluded 36 additional studies (Adamzcyk 2013; Al Shammeri 2014; Arnoldi 1976; Benigni 2013; Blazek 2013; Buhs 1999; Chant 1979; Couzan 2009; Diamand 2012; Diehm 1996; DRKS00008829; DRKS00012258; DRKS00014743; Fentem 1976; Genzel 1991; Gronbaek 1991; Häfner 2000; Häfner 2001; Jeanneret 2014; Labropoulos 1994; Lattimer 2017; Lord 2004; Moehrle 2007; Mosti 2010; Mosti 2012; Muller‐Buhl 1998; NCT01793194; Park 2013; Pohlmann 1997; Raj 1981; Saliba 2020; Vayssairat 2000; Weiss 1999a; Westphal 2019; Wolff 2011; Zajkowski 2002).

In total, we excluded 61 studies, some for more than one reason.

Eighteen studies included participants who had a surgical intervention or sclerotherapy, either as a randomised alternative to stockings or as an initial treatment prior to adjuvant therapy with compression (Abramowitz 1973; Biswas 2007; Bond 1997; Bond 1999; Chant 1979; Hamel‐Desnos 2008; Hamel‐Desnos 2010; Houtermans‐Auckel 2009; Makin 1982; Mariani 2011; Melrose 1979; Mosti 2009; O'Hare 2010; Perhoniemi 1983; Raj 1981; Raraty 1999; Weiss 1999b; Zajkowski 2002).

Sixteen studies did not include participants with diagnosed varicose veins at recruitment; generally, the participants in these articles were either healthy or were diagnosed with other forms of venous disease, such as ulceration or superficial venous insufficiency (Austrell 1995; Blazek 2013; Couzan 2009; Derman 1989; Diamand 2012; Fentem 1976; Genzel 1991; Gronbaek 1991; Guest 2003; Moehrle 2007; NCT01793194; Rabe 2010; Saliba 2020; Schul 2009; Thaler 2001; Weiss 1999a). In one study it was unclear if planned participants had varicose veins (DRKS00014743).

Three studies did not use hosiery as their method of compression (DRKS00008829; Griffin 2007; Mosti 2012). One study used antiembolism stockings (Pohlmann 1997).

Twelve studies did not stratify results by CEAP (Adamzcyk 2013; Al Shammeri 2014; Benigni 2003; Buhs 1999; Häfner 2000; Häfner 2001; Jeanneret 2014; Lattimer 2017; Mosti 2010; Muller‐Buhl 1998; Vayssairat 2000; Wolff 2011).

Three studies did not stratify results by different study populations: healthy participants and participants with varicose veins (Arnoldi 1976; Lord 2004), clinical gravitational disease and participants with varicose veins (Gandhi 1984).

One study was designed to assess the donning and taking off of compression stockings (Benigni 2013), and one study reported on a preliminary study investigating a 'novel leg supporter' (Park 2013). One study compared compression with horse chestnut extract and placebo capsules (Diehm 1996). One study planned outcomes not relevant for the review (DRKS00012258). Labropoulos 1994 investigated immediate and long‐term effects of stocking use with measurements taken at end of study period or four weeks after stopping use of stockings. All participants wore compression stockings. Westphal 2019 compared two stockings with same pressure end length, with the only difference being that one stocking had integrated care.

The final study that could potentially have been included was by Mosti 2011. However, this study included participants with CEAP classification C2 to C5 and reported no subgroup analysis of participants with a CEAP classification of C2 to C4. We contacted the study author to ask if this analysis had been undertaken, but received no reply.

Ongoing studies

We identified five new ongoing studies (DRKS00012259; NCT01402921; NCT03429959; NCT03743597; RBR‐5n9cmf), in addition to the ongoing study previously reported (NCT00766974). For details of all ongoing studies, see the Characteristics of ongoing studies table.

Risk of bias in included studies

See risk of bias sections of the Characteristics of included studies table, Figure 2, and Figure 3.

2.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

3.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Five studies reported adequate sequence generation and were at low risk of bias (Cazaubon 2013; Couzan 2012; Heidarimoghadam 2020; Kakkos 2018; Riebe 2018). The remaining studies did not describe the sequence generation sufficiently to allow a clear judgement and were therefore at unclear risk of bias (Anderson 1990; Chant 1985; Chant 1989; Chauveau 2000; Coughlin 2001; Jones 1980; Jungbeck 1997; Mariani 2013).

Five studies reported adequate allocation concealment and were at low risk of bias (Cazaubon 2013; Couzan 2012; Kakkos 2018; Mariani 2013; Riebe 2018). The remaining studies did not describe the allocation sequence sufficiently to allow a clear judgement and were therefore at unclear risk of bias (Anderson 1990; Chant 1985; Chant 1989; Chauveau 2000; Coughlin 2001; Heidarimoghadam 2020; Jones 1980; Jungbeck 1997).

Blinding

It is difficult to blind participants when using compression stockings as an intervention. It is obvious to the participant whether they are wearing a compression stocking or not. It is likely that it was for this reason that many studies did not report blinding of the participants. If a study compared different types of stocking, blinding of the participants was not assumed unless stated. If a study used only one type and pressure of stocking, and participants had been randomised to wear or not wear stockings, it was assumed that the participants were not blinded unless otherwise stated.

Three studies reported blinding of participants and personnel and were at low risk of performance bias (Couzan 2012; Kakkos 2018; Riebe 2018). Cazaubon 2013 was an open, non‐blinded cross‐over trial and was at high risk of bias. Heidarimoghadam 2020 did not report blinding, but the study authors reported that the intervention group wore stockings and only this group were sent stockings, suggesting both participants and personnel were aware of which group they were in; so this was at high risk of bias. The remaining studies were at unclear risk of bias due to lack of information around blinding of participants and personnel (Anderson 1990; Chant 1985; Chant 1989; Chauveau 2000; Coughlin 2001; Jones 1980; Jungbeck 1997; Mariani 2013).

Four studies reported blinding of outcome assessors and were at low risk of detection bias (Chant 1985; Couzan 2012; Kakkos 2018; Riebe 2018). Cazaubon 2013 was an open, non‐blinded cross‐over trial and was at high risk of bias. The remaining included studies were at unclear risk of bias due to lack of information around blinding of outcome assessors (Anderson 1990; Chant 1989; Chauveau 2000; Coughlin 2001; Heidarimoghadam 2020; Jones 1980; Jungbeck 1997; Mariani 2013).

Incomplete outcome data

For most studies there was insufficient information available to make a low or high risk of bias judgement on the completeness of outcome data. Therefore, eight included studies were at unclear risk of attrition bias (Anderson 1990; Cazaubon 2013; Chant 1985; Chauveau 2000; Coughlin 2001; Couzan 2012; Jones 1980; Jungbeck 1997). In some studies, although reasons for dropouts or withdrawals were given, it was not possible to determine from the results whether all participants were included or had completed the course of treatment. For example, in the studies by Chauveau 2000 and Anderson 1990, the results tables provided mean measures, not permitting the reader to determine if all participants' results were included. The remaining five studies were at low risk of attrition bias (Chant 1985; Heidarimoghadam 2020; Kakkos 2018; Mariani 2013; Riebe 2018).

Selective reporting

We judged four studies at low risk of reporting bias (Cazaubon 2013; Couzan 2012; Kakkos 2018; Riebe 2018). The remaining studies provided insufficient information to permit a low or high risk of bias judgement on selective reporting and were therefore at unclear risk of bias; the study protocols were not available and text reporting prespecified outcomes was not clear (Anderson 1990; Chant 1985; Chant 1989; Chauveau 2000; Coughlin 2001; Heidarimoghadam 2020; Jones 1980; Jungbeck 1997; Mariani 2013).

Other potential sources of bias

Cazaubon 2013, Couzan 2012, Heidarimoghadam 2020, Jungbeck 1997, Mariani 2013, and Riebe 2018 were at low risk of bias as there were no other potential sources of bias.

Seven studies were at unclear risk of other bias (Anderson 1990; Chant 1985; Chant 1989; Chauveau 2000; Coughlin 2001; Jones 1980; Kakkos 2018). Anderson 1990 did not use wash‐out periods between the various treatment periods. Chant 1985 reported "we accept that the study was biased towards surgery because patients were taken from the waiting list …" The participants in Chant 1989 were prescribed stockings tailored to their degree of venous insufficiency, which could mean people were given different types and pressures of stocking. This may have had an impact on their compliance. In Chant 1989 and Coughlin 2001, there were high drop‐out rates following the initial prescription of stockings (Chant 1989: 39%; Coughlin 2001: 32%), which may have affected the results. Chauveau 2000 and Jones 1980) had very small numbers of participants with varicose veins (both had 10). Kakkos 2018 was underpowered for most symptoms other than pain/aching.

Effects of interventions

See: Table 1; Table 2

The main objective of this review was to assess the effectiveness of compression stockings in the initial treatment of varicose veins in people without venous ulceration. All included studies assessed one or more of the prespecified outcomes for this review.

Compression stockings compared with no treatment or placebo stockings

Four studies compared compression stocking with either no stocking or PS (Coughlin 2001; Heidarimoghadam 2020; Kakkos 2018; Mariani 2013). Anderson 1990 assessed the effect of compression stockings and oxerutins, alone and in combination.  As the groups were identifiable for analyses we were able to use the information relating to the stocking plus placebo versus placebo arms. Therefore, in total five studies were available for assessment in this comparison.

Primary outcomes

Change in symptoms

Four studies assessed change in symptoms (Anderson 1990; Heidarimoghadam 2020; Kakkos 2018; Mariani 2013). Individually, all studies reported a subjective improvement in symptoms by the end of the trial, but these were not always analysed comparing the two randomised arms of the trials and were therefore subject to bias. Due to the differences in the way the studies assessed and reported change in symptoms we were unable to pool the studies. We judged the certainty of the evidence to be low because of risk of bias and inconsistency (Table 1).

Two studies used a VAS to report and evaluate symptoms including pain, ankle swelling, tired legs, restless legs, night cramps, heaviness, itching and distress from the cosmetic appearance (Anderson 1990; Kakkos 2018). Anderson 1990 provided VAS results for change in each of the individual symptoms using means and standard errors while Kakkos 2018 provided VAS results for change in each of the individual symptoms using means and standard deviations (SD). Heidarimoghadam 2020 used the CPGS (to assess pain) and MFQ (to assess fatigue) and are reported as change in symptoms.

Mariani 2013 indicated they planned to assess patient mobility as a secondary endpoint. They reported that the patients' "joint mobility and activity (measured with the Norton scale) were very good for all patients in both groups," but it was unclear if this was at baseline or at the end of the study.

Anderson 1990 reported no statistically significant differences in VAS scores after any of the treatments. However, the use of oxerutins alone and compression hosiery alone appeared to reduce symptoms more than the placebo, as seen in the VAS scores. For example, for the symptom of swelling the mean VAS score for the placebo was 35.3; the mean score for hosiery plus placebo was 28.2; the mean score for oxerutins was 31.5; and the mean score for hosiery plus oxerutins was 32.4. These observed improvements were true for all symptoms with the exception of distress from cosmetic appearance.

Kakkos 2018 reported on dull pain or aching of the leg with the varicose veins, and leg symptoms such as heaviness, swelling sensation, varicose vein throbbing, burning sensation, paraesthesiae, night cramps and restless legs, and insomnia, all graded by the participant using VAS (0 to 10) at baseline and after one week of compression (see Table 3). Fourteen of 15 participants in each group completed VAS after one week of wearing stockings. Kakkos 2018 reported that after one week, the active stockings were more effective than PSs in reducing pain/aching; there were improvements for the feeling of swelling and paraesthesiae, but these were not statistically significant. All but two participants randomised to active stockings reported either some improvement (three participants) or complete resolution (nine participants) of pain/aching. There was improvement of more than 50% of pain/aching in 11 participants (mean decrease of VAS 5.5 (SD 2.9)). In the placebo group, two participants reported complete resolution of pain, five reported some improvement, seven reported no change and none reported deterioration. Four participants reported improvement of more than 50% of pain aching in the placebo group. There was no clear difference in modified VCSS score after one week between the placebo and class 1 stocking groups (3.8 (SD 1.5) for PS and 3.1 (SD 1.2) for class 1 stocking; P = 0.22).

1. Results of symptoms scoring using 0–10 VAS after one week of stocking use in the index leg (Kakkos 2018).

Symptoms	Placebo stockings (14 participants) mean (SD)	Class 1 stockings (14 participants) mean (SD)	P value
Pain/aching	4.5 (2.8)	1.7 (3.0)	0.02
Heaviness	4.0 (3.1)	2.4 (3.1)	0.17
Swelling	3.3 (3.5)	0.9 (1.9)	0.03
Throbbing	1.4 (2.7)	0.9 (1.9)	0.10
Paraesthesia	2.1 (3.1)	0.2 (0.6)	0.04
Night cramps	0.9 (2.0)	0.0 (0.0)	0.14
Burning	2.4 (3.4)	0.8 (1.8)	0.14
Restless legs	0.0 (0.0)	0.0 (0.0)	N/A
Insomnia	0.0 (0.0)	0.9 (2.4)	0.18

N/A: not applicable; SD: standard deviation.

Heidarimoghadam 2020 reported chronic pain and muscle fatigue. Information was collected via the CPGS and MFQ. Both pain and fatigue were assessed as change in symptoms. When comparing the baseline scores with scores after the intervention at three months, the mean scores for pain in lower extremities decreased in the intervention group while they increased in the control group (intervention group: pain scores preintervention: mean 32.4 (SD 28.49), pain scores postintervention: mean 30.7 (SD 26.31); P = 0.015; control group: pain scores pre‐intervention: mean 26.97 (SD 24.33), pain scores postintervention: mean 29.97 (SD 24.66); P = 0.015). Pain scores were not clearly different between intervention and control groups at baseline and postintervention (baseline: MD 5.43, 95% CI –6.98 to 17.84; postintervention: MD 0.73, 95% CI –11.22 to 12.68). Heidarimoghadam 2020 did not present an analysis comparing pain scores between the intervention and control group after the intervention; our own analysis (not shown) found no clear differences in pain scores between the intervention and control group after the intervention. Heidarimoghadam 2020 assessed fatigue in the left and right leg separately for the intervention and control groups. When comparing pre‐ and postintervention scores, there was less fatigue after three months in the intervention group while there was more fatigue in the control group. After three months, the left side and right side showed no clear differences between the intervention and control group (left side: MD –1.17, 95% CI –2.58 to 0.24. P = 0.10; right side MD –0.86, 95% CI –2.25 to 0.53).

Physiological measures

Two studies assessed physiological measures (Kakkos 2018; Mariani 2013). Due to the different physiological measures assessed we were unable to pool the studies. We judged the certainty of the evidence to be very low because of risk of bias, inconsistency, imprecision and indirectness (Table 1).

Kakkos 2018 studied ankle circumference in millimetres after one week of compression. Kakkos 2018 reported that ankle circumference readings were not significantly different at baseline and after one week for the index leg for the two study groups (after one week of compression: placebo group: mean 22.9 (SD 1.8); stocking group: mean 22.7 (SD 1.2); P = 0.69).

Mariani 2013 assessed reduction of oedema using duplex scan sonography after three and seven days. Oedema was significantly reduced after three days of treatment with MCS (22 (84.6%) participants had no oedema; P = 0.002). There was a further improvement between days three and seven for the MCS group (oedema was reduced in 25 (96.2%) participants). Mean time to oedema reduction was 3.5 days for in the MCS group. MCS was also effective in reducing leg circumference and subcutaneous thickness. PS had no effect on oedema, leg circumference or subcutaneous thickness. Mariani 2013 reported that the differences between the two treatment groups were statistically significant in favour of MCS.

Secondary outcomes

Complications

Three studies reported complications as side effects (Anderson 1990; Coughlin 2001; Kakkos 2018). Due to the differences in the way they reported complications, we were unable to pool the studies. We judged the certainty of the evidence to be very low because of risk of bias, inconsistency and imprecision (Table 1).

Anderson 1990 reported the side effects of abdominal pain, headache and nausea; however, this was a four‐arm cross‐over trial that also included taking oxerutins and a placebo tablet, which may have caused the reported side effects. The study reported that the side effects were similar in all four arms and none were severe or long lasting, but they presented no results.

Coughlin 2001, in which compliance was the main outcome, irritation was given as a reason why some participants stopped wearing stockings but there was no information regarding the severity. The authors stated that abdomen size was likely to be the cause of the discomfort because the participants were pregnant women and the intervention was compression tights.

Kakkos 2018 reported complaints of complications of active and PS groups in addition of any pruritus (itching) (graded on a 0 to 10 VAS). One participant allocated to the PS group reported pruritis after wearing stockings. Another participant, allocated to the active stockings group, reported occurrence of thigh cramps. A third participant, also allocated to the active stockings group, reported that the top band of the stockings was too tight.

None of the trials reported severe side effects.

Compliance

Three studies reported compliance (Coughlin 2001; Kakkos 2018; Mariani 2013). We did not carry out meta‐analysis because of the differences in compliance assessments between the studies. We judged the certainty of the evidence to be low because of risk of bias and imprecision (Table 1).

Coughlin 2001 had a high initial drop‐out rate: 33% of participants (pregnant women with varicose veins) did not want to take part in the study once randomised to wearing compression tights.

The trials assessed compliance differently. Coughlin 2001 relied on self‐reports from the women as to when they stopped wearing the tights. As their pregnancies progressed, increasing numbers of women rejected the compression tights: seven women wore them up to 20 weeks, four to 28 weeks, 14 to 34 weeks, two to term and four to 6 weeks' postpartum. There were no statistical calculations performed. Coughlin 2001 found a general low compliance rate. Generally, non‐compliance appeared to be greatest when the hosiery was initially prescribed, and reasons given by participants for not wearing them included discomfort, application, appearance, not effective and that they caused irritation. Coughlin 2001 concluded that tights were unacceptable in pregnant women due to their abdominal size.

Kakkos 2018 assessed compliance by asking the participants to complete daily log sheets entering the hours they had used the stockings. Kakkos 2018 reported good compliance during the one‐week trial, with the mean daily use of PS of 8.0 hours and of active stocking of 10.2 hours. Kakkos 2018 further reported there was no association between daily stocking use and absolute reduction of the primary efficacy outcome pain/aching using VAS in the active stockings group.

Mariani 2013 assessed compliance by the number of days the participants wore the stockings for at least 10 hours per day. There was limited information on compliance but Mariani 2013 did report good compliance in 86.7% (26 participants) of the MCS group.

In addition to Coughlin 2001, Kakkos 2018, and Mariani 2013, Anderson 1990 indicated they assessed self‐reported measures of how long the participants wore stockings every day but did not report on this in their study paper.

Comfort, tolerance and acceptability of wearing stockings

Two studies reported on comfort, tolerance and acceptability of wearing stockings (Coughlin 2001; Mariani 2013). We did not carry out meta‐analysis because of the differences in assessments of comfort and tolerance between the studies. We judged the certainty of the evidence to be very low because of risk of bias, inconsistency and imprecision (Table 1).

Coughlin 2001 reported that an increasing number of women stopped wearing the tights as their pregnancy progressed. Only 55% stated that the tights were still comfortable at 34 weeks' gestation, with the size of their abdomen in late pregnancy being the most significant factor associated with stocking rejection. Coughlin 2001 concluded that Class 1 compression tights are not acceptable to pregnant women because of abdominal size; a different type of hosiery may be more suitable.

Regarding the tolerability of the class 2 stockings compared with the PS, Mariani 2013 reported that the "difficulties encountered when wearing stockings were significantly greater with MCS compared with PS, but only the amount of discomfort in the afternoon differed significantly. Hindrance of normal activities and daytime discomfort was not more pronounced with MCS (day time discomfort: MCS 0.46 (SD 0.45), PS: 0.26 (SD 0.39); P = 0.086)." Mariani 2013 concluded that the difficulties wearing MCS and the experienced daytime discomfort was associated with older age.

Difficulty of donning the stockings or ease of application

One study assessed difficulty of donning the stockings or ease of application (Mariani 2013).

Mariani 2013 reported that difficulty donning and removing the stockings was more pronounced in the MCS group compared with the PS (measured using VAS in cm: MCS mean 0.22 (SD 0.31) cm; PS: 0 (SD 0) cm; P = 0.001).

Quality of life

One study reported QoL (Heidarimoghadam 2020). We judged the certainty of the evidence to be low because of risk of bias and imprecision (Table 1).

Heidarimoghadam 2020 assessed quality of working life using the AVVQ reporting QoL with a score of the questionnaire for the intervention and control group both before and after the intervention. There was no clear difference in AVVQ score between baseline and follow‐up in the intervention group (baseline: mean 19.53 (SD 10.05); follow‐up: mean 20.43 (SD 10.12); P = 0.27), but reported a worsened score between baseline and follow‐up in the control group (baseline: mean 21.85 (SD 14.53); follow‐up: mean 23.34 (SD 14.03); P = 0.029). The study authors concluded that the use of compression stockings did not influence QoL. They provided no comparison of QoL between the intervention and control group after the intervention; our own analysis (not shown) found no clear differences between the intervention and control group.

Compression stockings compared with different compression stockings

Eight studies assessed one type or pressure of stocking against another (Cazaubon 2013; Chant 1985; Chant 1989; Chauveau 2000; Couzan 2012; Jones 1980; Jungbeck 1997; Riebe 2018).

Primary outcomes

Change in symptoms

Five studies assessed change in symptoms (Chant 1985; Couzan 2012; Jones 1980; Jungbeck 1997; Riebe 2018). Individually, all studies reported a subjective improvement in symptoms by the end of the trial, but did not analyse them comparing the two randomised arms of the trials and were therefore subject to bias. Due to the differences in the way studies assessed and reported change in symptoms, we were unable to pool the studies. We judged the certainty of the evidence to be low because of risk of bias and inconsistency (Table 2).

Jungbeck 1997 used a VAS to report and evaluate symptoms including pain, ankle swelling, tired legs, restless legs, night cramps, heaviness, itching and distress from the cosmetic appearance. Jungbeck 1997 combined their results, providing only a median percentage change in all subjective symptoms (such as pain, swelling, tired legs, restless legs and cramps) before and after wearing class 1 (20 mmHg) versus class 2 (30 mmHg) stockings. Results were given as participant self‐assessments of subjective symptoms expressed as median of VAS (in per cent). For class 1 stockings, there was a reduction of 28.2%, and for class 2 stockings there was a reduction of 31.3%. Jungbeck 1997 reported no significant difference between the two groups.

Chant 1985 and Jones 1980 used participant self‐reporting of symptoms and gave a more general result as to whether symptoms had improved or not at different time points in each study. Chant 1985 reported the number of participants who experienced improved symptoms with wearing 30 mmHg to 40 mmHg stockings (42/53 participants) and 40 mmHg to 50 mmHg stockings (40/51 participants). Jones 1980 provided no data for changes in symptoms and simply reported "patients with varicose veins were relieved of aching symptoms by both sorts of stocking."

Riebe 2018 reported on changes in VCSS indicating that oedema, inflammation and pain diminished significantly during one week of compression. The mean VCSS at baseline for GECS was 4.2, with a final VCSS score after one week of compression of 3.2 (overall decrease in VCSS score –1). The mean baseline VCSS score for PECS was 4.2, with a final VCSS score after one week of 3.9 (overall decrease in VCSS score –0.3). Riebe 2018 concluded that both GECS and PECS were effective, but that GECS were more effective than PECS (P < 0.001).

Couzan 2012 reported on improvement of pain/heavy legs scores, DVT, SVT, PE and ulcer, and VCSS, at one month, three months and six months. The composite success outcome was defined as an improvement in pain or heavy legs without onset of either ulcer or thromboembolism. At three months, the rate of success was significantly higher in the progressive stocking group (70.2%) compared to 59.6% in degressive stocking group (RR 1.18, 95% CI 1.02 to 1.37; P = 0.03). The difference was explained mainly by the higher rate of symptom improvement in the progressive stocking group. At one month and six months there were no clear differences in composite success between the progressive and degressive groups (one month: RR 0.96, 95% CI 0.81 to 1.14; six months: RR 0.92, 95% CI 0.79 to 1.06).

At one month, there were thromboembolic events in 3/202 participants in the degressive stockings group (1 SVT, 1 DVT, 1 PE). At three months, there were thromboembolic events in 2/195 participants in the progressive stockings group (two DVTs) and 4/197 participants in the degressive stockings group (one SVT, two DVT and one PE). At six months, there were thromboembolic events in 5/189 participants in the progressive stockings group (one SVT, four DVT) and 6/193 participants in the degressive stockings group (three SVT, three DVT and one PE; one participant had more than one event). There were no ulcers during the study period.

At three months, Couzan 2012 used a modified version of the VCSS ("stripped from its 'compressive therapy' item"). Couzan 2012 reported no clear differences in VCSS scores (progressive stockings: mean 3.2 (SD 1.6); degressive stockings: mean 3.1 (SD 1.6); P = 0.60).

Physiological measures

Five studies assessed physiological measures (Cazaubon 2013; Chauveau 2000; Jones 1980; Jungbeck 1997; Riebe 2018). Due to the differences in the way studies assessed physiological measures, we were unable to pool the studies. We judged the certainty of the evidence to be very low because of risk of bias, inconsistency, indirectness and imprecision (Table 2).

Two studies used foot volumetry to measure expelled volume (EV), the relative expelled volume related to 100 mL of foot volume (EVR or EVrel), rate of refilling of the foot after exercise (Q), and the quotient combining both aspects of functional assessment (Q/EVR or Q/EVrel). This quotient is a measure of the blood expelled by the musculovenous pump in the leg and the prevention of reflux by venous valves, both of which are important for the prevention of varicose veins. Other measures were taken but only these four were consistent between the two studies (Jones 1980; Jungbeck 1997). Both studies investigated differences between stockings providing 20 mmHg pressure and those providing 30 mmHg to 40 mmHg pressure. One study was a cross‐over trial where participants wore each type of stocking for three weeks, with one week of not wearing stockings between (Jones 1980). The other trial was a parallel group study, where participants were randomised to one of two different types of stocking for eight weeks (Jungbeck 1997). Because there were only two studies that assessed these measures, and they were of different methodology, it was decided not to combine them in a comparison table or meta‐analysis. Both studies also had poor levels of reporting: Jungbeck 1997 used only medians (and 95% CI) to report initial values and values at eight weeks for both class 1 (20 mmHg) and class 2 (30 mmHg) stockings. Jones 1980 presented the results in a graph for each physiological measure. These results would have to be used cautiously if a meta‐analysis had been produced.

Compared with baseline values, Jones 1980 reported in their varicose vein group (10 participants) an improved performance for EV (20 mmHg stocking: 20%; 30 mmHg to 40 mmHg stocking: 8%), EVR (20 mmHg stocking: 30%; 30 mmHg to 40 mmHg stocking: 15%), Q (20 mmHg stocking: 50%; 30 mmHg to 40 mmHg stocking: 20%) and Q/EVR (20 mmHg stocking: 20%; 30 mmHg to 40 mmHg stocking: 35%), although these were reported as not statistically significant. Jungbeck 1997 reported significant improvement in EV and EVrel after wearing class 1 (20 mmHg) stockings for eight weeks compared with the baseline values (EV: baseline: median 12.4, 95% CI 10.5 to 12.7; at 8 weeks: median 14.7, 95% CI 12.8 to 16.4; P < 0.05; EVrel: baseline: median 1.09, 95% CI 0.87 to 1.23; at 8 weeks: median 1.38, 95% CI 1.10 to 1.56; P < 0.01). Jungbeck 1997 reported no significant differences for Q and Q/EVrel for class 1 (20 mmHg) stockings or for EV, EVrel, Q and Q/EVrel for class 2 (30 mmHg) stockings.

One study used air plethysmography to measure arterial inflow (AI), venous volume (V50) and maximum venous outflow (MVO) as part of the assessment for a tourniquet effect while wearing stockings (Chauveau 2000). There were no significant changes in any of these measures while wearing class 1 (10 mmHg to 15 mmHg) stockings. There were significant reductions for AI (mean 1.22 mL/second to 0.93 mL/second) and venous volume (98 mL to 80 mL) while wearing class 2 (15 mmHg to 20 mmHg) stockings. However, this study was not designed to compare the effectiveness of the stocking.

Riebe 2018 assessed volume reduction of two sections of the lower limb, reporting that the volume reductions in the distal lower leg and foot and lower leg and foot following GECS and PECS were not significantly different. Interface pressure measurements demonstrated that GECS had a higher pressure at level B1 (12 cm proximal to the inner ankle) compared to level C (maximal calf circumference) and, as expected, with the inverse seen by PECS (i.e. a higher pressure at the calf compared with the distal leg).

Riebe 2018 assessed function of the calf muscle pump and venous drainage (ejection fraction (EF) and venous filling index (VFI). EF data were available for 30 participants. EF before and during wearing stockings (both types) showed improvement (P < 0.001), and comparatively the GECS resulted in greater improvement in EF than PECS (P = 0.01). Venous filling was assessed as the reduction in blood volume per time in standing position with compression: using difference in VFI, delta VFI (difference with versus without stocking). There were no clear differences between stockings (P > 0.05), but differences were identified between healthy volunteers and participants with chronic venous insufficiency.

Cazaubon 2013 investigated change in diameter of deep and superficial veins, change (amplitude and direction) in venous reflux and pressure of stockings. There were small differences between the progressive and degressive stocking groups, particularly in the great saphenous vein and calf but none were statistically significantly different. Cazaubon 2013 reported that the objective reflux on the popliteal vein and the small saphenous vein did not vary significantly, neither in duration nor in amplitude, either with degressive or progressive compression although there were no specific data. Cazaubon 2013 also reported that the measurements confirmed that the stockings exerted constant pressures during the two successive uses while confirming the differences in pressures between the two types of stocking. Again, there were no specific data.

Secondary outcomes

Complications

Due to the differences in the way complications were reported, we were unable to pool the studies. We judged the certainty of the evidence to be low because of risk of bias and inconsistency (Table 2).

One small study (10 participants) assessed complications as a main outcome (Chauveau 2000). The study tested two different pressures of stocking (class 1 (10 mmHg to 15 mmHg) and class 2 (15 mmHg to 20 mmHg)) to assess if there was any difference in producing a tourniquet effect while they were being worn. A tourniquet effect is a possible side effect of wearing compression stockings that could impede venous return (Chauveau 2000). For people who already experience arteriopathy such a side effect could potentially lead to ischaemia of the surrounding tissues. Chauveau 2000 reported no evidence of a tourniquet effect of class 1 or 2 below‐knee stockings.

Three other studies reported side effects.

Chant 1989 recorded the reasons why participants did not wear the compression stockings. These included "caused irritation," which affected 4/40 participants.

Couzan 2012 reported stockings‐related harm at one month, three months and six months. Symptoms ranged from allergy, itching, and constriction and tightness. At three months, 81/199 (43.3%) participants in the progressive group reported at least one harm compared to 92/202 (49.5%) participants in the degressive group. At six months, 89/199 (49.2%) participants in the progressive group reported at least one harm compared to 96/202 (50.5%) participants in the degressive group. At all time points, Couzan 2012 reported no clear differences in number of participants reporting at least one harm between the progressive and degressive stocking groups.

Riebe 2018 reported side effects. These included sweating, itching and skin dryness in both the GECS and PECS groups with no clear differences between them. Riebe 2018 reported more cases of tingling of the skin and tightness in the GECS group compared with the PECS groups (tingling: P = 0.038; tightness: P = 0.0001), and constrictions at the dorsal ankle joint were more frequently reported as particularly painful (P = 0.047).

None of the trials reported severe side effects.

Compliance

Two studies reported compliance (Chant 1989; Couzan 2012). We did not carry out a meta‐analysis because of the differences in compliance assessments between the studies. We judged the certainty of the evidence to be low because of risk of bias and indirectness (Table 2).

Chant 1989 had a high initial drop‐out rate; 30% of participants (22/66 participants wanted symptomatic relief of varicose veins prior to elective surgery for the condition), did not collect the compression stockings they were randomised to.

Chant 1989 completed random visits to participants' houses approximately six weeks after the stockings had been prescribed to assess whether participants were wearing the stockings. Chant 1989 reported that overall compliance with treatment for the 66 participants entered into the trial was 32%. Twenty‐two participants failed to collect stockings and four participants underwent surgery before having had the chance to assess the effects of the stocking. Of the remaining 40 participants, 12/18 (67%) Medi Plus participants wore their stockings compared with 9/22 (41%) in the Sigvaris group. Chant 1989 found a generally low compliance rate, but neither type of stocking studied produced significantly more or less compliance than the other. Generally, non‐compliance appeared to be greatest when the hosiery was initially prescribed, and reasons given by participants for not wearing them included discomfort, application, appearance, not effective and that they caused irritation.

Couzan 2012 interviewed their participants for details about compliance at one month, three months and six months, categorising responses into "never, occasionally or rather regularly," "most of the time" and "from morning to bed time." Couzan 2012 reported no clear differences in compliance between the progressive and degressive stockings at each of the time points assessed.

Comfort, tolerance and acceptability of wearing stockings

Four studies reported comfort, tolerance and acceptability of wearing stockings (Chant 1985; Couzan 2012; Jones 1980; Riebe 2018). We did not carry out a meta‐analysis because of the differences in assessments of comfort and tolerance between the studies. We judged the certainty of the evidence to be very low because of risk of bias, inconsistency and indirectness (Table 2).

Chant 1985 reported that 80/104 (77%) participants claimed that the stockings were comfortable (study authors did not provide data to show which pressure (30 mmHg to 40 mmHg or 40 mmHg to 50 mmHg) stocking was more comfortable). In the remaining participants, the main cause of discomfort was not simply that the stockings were too tight but there was no further information as to what was the cause of discomfort. Chant 1985 reported that most participants (although no numbers were reported) found the higher pressure stockings tolerable and about one quarter (presumed to be 25% of 51 participants in the group so approximately 13) found them sufficiently acceptable that they decided not to undergo surgery. Chant 1985 noted they could have increased acceptability of the stockings by varying their weight and length (e.g. to above knee or tights), but for consistency in the trial, they did not want to. Chant 1985 also suggested that to presume lower pressure stockings were more acceptable may be incorrect.

Couzan 2012 reported similar levels of discomfort of wearing stockings between the progressive and degressive groups at three months (progressive stockings: none or mild discomfort 142/199 (75.9%) participants; important discomfort 45/199 (24.1%) participants; degressive stockings: none or mild discomfort 134/202 (72.4%) participants; important discomfort 51/202 (27.6%) participants). There were similar levels of discomfort between the groups at six months, but the level of discomfort was considerably smaller (progressive stockings: none or mild discomfort 161/199 (89.4%) participants; important discomfort 19/199 (10.6%) participants; degressive stockings: none or mild discomfort 173/202 (91.1%) participants; important discomfort 17/202 (8.9%) participants).

Jones 1980 reported that 25/30 participants preferred Sigvaris to Eesiness. Five participants in the normal deep veins and no varicose veins group did not. All participants (10/10) with superficial varicose veins reported relief of aching symptoms by both stockings. Seven of 10 participants with superficial varicose veins and all postphlebitic participants (10/10) complained of Eesiness stockings slipping down.

Riebe 2018 assessed comfort using 4‐point scale (0 not present, 1 low present, 2 moderate present, 4 highly present). There was more slipping down of the stockings towards the foot with PECS compared with GECS (frequency of slipping: GECS 25% versus PECS 81.3%; P < 0.001; mean score GECS 0.34 versus PECS 1.47). There was more strangling and tightness of the leg with GECS (strangling: mean score GECS 1.19 versus PECS 0.80; P < 0.05; tightness of the leg: mean score GECS 1.06 versus PECS 0.48; P < 0.001).

Difficulty of donning the stockings or ease of application

Four studies assessed or reported on difficulty of donning the stockings or ease of application (Cazaubon 2013; Chant 1989; Couzan 2012; Riebe 2018). We did not carry out a meta‐analysis because of the described differences in assessments between the studies.

Cazaubon 2013 assessed difficulty donning of stockings using VAS. The mean VAS score for progressive stockings was 13.7 (SD 16.6) and for degressive stockings was 33.3 (SD 17.9) (median scores: progressive: 8.5; degressive 33.5). The study authors concluded that donning of progressive stockings was significantly easier than for degressive stockings (P = 0.0005).

Chant 1989 reported that 1/22 participants in the Sigvaris arm and 1/18 participants in the Medi Plus arm stopped wearing the stockings because of problems with their application.

Couzan 2012 reported that, at three months, 152/199 (81.3%) participants in the progressive stockings group judged stockings were easy to apply compared with 92/202 (49.7%) participants in the degressive stockings group (P < 0.0001). There were similar results at six months (156/199 (86.2%) participants in the progressive group versus 108/202 (57.1%) participants in the degressive group; P < 0.0001).

Riebe 2018 reported more difficulty donning (strenuous donning) using a 4‐point scale (0 not present, 1 low present, 2 moderate present, 4 highly present) with GECS compared with PECS (frequency of difficulty donning: GECS 89.1% versus PECS 50.0%; P < 0.001; mean score GECS 1.63 versus PECS 0.58).

Quality of life

None of the studies comparing compression stockings with different compression stockings assessed QoL.

Discussion

Summary of main results

This review has summarised the evidence for the use of graduated compression hosiery or stockings for the treatment of primary varicose veins in people without venous ulceration. We included 13 studies with 1021 participants with varicose veins without healed or active venous ulceration. One or more included study assessed the prespecified outcomes of the review. There were no severe or long lasting side effects.

For the comparison of compression stockings with no treatment or PS, subjectively, four studies reported improvement in change in symptoms (low‐certainty evidence). This was also true for the comparison of compression stockings with compression stockings, with all five included studies reporting a subjective improvement by the end of the trial (low‐certainty evidence). However, due to the different ways that studies assessed change in symptoms, no clear conclusion could be made.

Physiological measures (oedema) improved in one of the two studies that included a comparison of compression stockings with no treatment or PS (very‐low certainty evidence). For the studies that compared compression stockings with different compression stockings, generally there were no clear differences between groups when the assessment of physiological measures was undertaken (very‐low certainty evidence). Due to the different ways in which authors reported their results, it was not possible to pool the data in a meta‐analysis.

Three studies reported complications by assessing side effects. Due to the differences in the way authors reported complications, it was not possible to pool the data. For the studies that compared compression stockings with no treatment or PS there was no clear difference between groups (very‐low certainty evidence). This was also true for the comparison of compression stockings with different compression stockings (low‐certainty evidence).

Four studies that compared stockings with placebo/no treatment and two studies that compared stockings with different stockings assessed compliance. In the stocking versus placebo/no treatment group, three studies reported usable results. Of these, one study reported a high initial dropout rate with generally low levels of compliance. The other two studies reported generally good compliance in the treatment group. Some reasons provided for non‐compliance included discomfort, application, appearance, not being effective and causing irritation (low‐certainty evidence). In the stocking versus stocking studies, there was no clear difference between the groups, with generally low levels of compliance reported (low‐certainty evidence).

Two studies that compared stockings with placebo/no treatment and four studies that compared stockings with different stockings assessed comfort, tolerance and acceptability of stockings. Comparing stockings with placebo/no treatment, comfort, tolerance and acceptability was affected by the study population. Compression tights were increasingly rejected by pregnant women when their pregnancy progressed, while in one study of non‐pregnant women, the stockings group showed no more hindrance of normal activities and daytime discomfort when compared with PS (very‐low certainty evidence). In the stocking versus different stocking comparison, two studies reported similar levels of tolerance and discomfort between the types of stocking (very‐low certainty evidence). Discomfort was the main reason for indicating a preference for one type of stocking over another.

One study reported on QoL showing no clear differences between the stocking and PS group (low‐certainty evidence).

No conclusions regarding the optimum length of compression stocking or optimum pressure could be made as there were no conclusive results from the included studies.

Not all included studies assessed the same outcomes or they used different ways to assess them, making pooling of studies impossible. In addition, many studies were small. The different populations studied also accounted for differences. Therefore, this review is unable to draw definitive conclusions with regards to the effect of compression stockings for varicose veins in people without healed or active venous ulceration for the outcomes assessed: change in symptoms, change in physiological measures, complications, compliance and QoL.

Overall completeness and applicability of evidence

The present Cochrane Review looked at compression stockings for initial treatment of varicose veins without healed or active venous ulceration. We excluded the use of compression stockings in other situations, such as after varicose vein surgery or in combination with other varicose vein treatments, or other situations in which compression stockings are used.

Although all the participants included in this review were diagnosed with varicose veins, as stated in the inclusion criteria, there was some variation in the type of participant. One study included only pregnant women, while other studies included participants who were on surgical waiting lists or had been referred to a relevant clinic. Such groups of participants may bias towards people who have sought medical intervention for their varicose veins.

Compliance varied between studies. The study including pregnant women reported poor compliance with high initial dropout rate following randomisation. Two other studies suggested good levels of compliance, however, there were limited data available to provide evidence to these statements, which were based on participant self‐reporting.

Differences in outcomes assessed and the way they were assessed and reported meant that studies were not easily comparable.

The lack of high‐certainty evidence identified in this review means that its potential impact on clinical practice is very limited. Although stockings are generally not found to completely reverse or eradicate the disease, observational findings (as mentioned in this review) suggest that they may subjectively improve symptoms. However, as other treatments that could help remove varicose veins completely and improve cosmetic appearance have become more viable and common in everyday practice (Whing 2021), people may prefer these to wearing compression stockings for long periods of time. In the UK, NICE recommends offering compression only if interventional treatment is ineffective and as first‐line therapy only in pregnant women (NICE 2013).

To answer the objective of this review, adequately powered trials that compare wearing stockings versus not wearing stockings are required.

Quality of the evidence

See Table 1; Table 2.

The review included 13 studies with 1021 participants with varicose veins without healed or active venous ulceration. Studies varied in sample size from 10 to 401. The risk of bias for many of the included studies was unclear as inadequate reporting did not permit a low risk or high risk of bias judgement (see Figure 2 and Figure 3). Seven of 13 studies were conducted between the late 1970s and early 2000s (Anderson 1990; Chant 1985; Chant 1989; Chauveau 2000; Coughlin 2001; Jones 1980; Jungbeck 1997). The age of some studies is likely to be the cause of the inadequate reporting. The current standard for reporting clinical trials, the CONSORT statement, was not developed until 1996 and earlier studies did not have such specific guidelines.

Not all included studies assessed the same outcomes or used different ways to assess them, making pooling of studies impossible. In addition, many studies were small. The different populations studied also accounted for differences, for example in relation to compliance for the study including pregnant women. For some outcomes, such as complication, there were few events reported.

Therefore, for both comparisons (compression stockings compared with no treatment or PS and compression stockings compared with different compression stockings) the certainty of evidence was very low or low.

Potential biases in the review process

This review followed a structured protocol that had been agreed by Cochrane Vascular (Shingler 2011). At least two review authors were involved in selecting relevant studies, assessing risk of bias, extracting data and assessing certainty of evidence.

Where necessary, we contacted study authors to gather further information. Not all study authors replied, meaning these studies had to be excluded as it was not clear if participants met the inclusion criteria or not. However, relevant data may have been missed by excluding these studies, if participants did actually meet the inclusion criteria, leading to bias. Only by receiving a reply from the study authors could this be resolved.

Statistical analyses in the form of meta‐analyses were not performed for any of the outcomes. This was primarily due to the differences in the way the studies assessed and reported outcomes.

Agreements and disagreements with other studies or reviews

One systematic review by Palfreyman 2009 examined the evidence regarding the effectiveness of compression hosiery in the treatment of varicose veins. The review included 25 studies, including RCTs, systematic reviews, non‐randomised studies and guidelines. This review also found methodological flaws in the included studies and concluded that the evidence for the benefit of compression hosiery for varicose veins was equivocal. No conclusion regarding the class or length of compression hosiery for effective management of varicose veins was made. Therefore, the results of the present systematic review would appear to agree with the review by Palfreyman 2009. They do state, however, that the incorrect application of compression hosiery can have serious consequences, including necrosis. This review found no evidence to support or disagree with this statement. Even though the outcomes and methods of this review were slightly different to Palfreyman 2009, the results showed that more research is required in this area, especially a large‐scale RCT. Currently the certainty of evidence does not permit a conclusive result.

More recent guidelines, such as those by NICE 2013 and Gloviczki 2011, report that stockings may be used if interventional therapy is ineffective or not appropriate but evidence is low or very‐low quality. NICE recommends offering compression only if interventional treatment is ineffective and as first‐line therapy only in pregnant women (NICE 2013). Within the guidelines by Gloviczki 2011, the authors recommend using compression therapy at a moderate pressure (20 mmHg to 30 mmHg) in knee‐high stockings (although they also noted that thigh‐high and tights are also available and may be appropriate) for people with symptomatic, simple varicose veins (CEAP C2). However, they also recommended that where patients are candidates for saphenous vein ablation, that this is provided over compression therapy. The authors noted that the evidence was limited and further data on the appropriate tension of elastic garments were required, as well as compliance being an issue for many patients. The recommendation for compression therapy is also reported for people with CEAP C3 to C6. It is important to note that the authors in the guidelines by Gloviczki 2011 noted that the evidence for their recommendation was scored 2 (weak) and the evidence available was "low or very low quality."

Authors' conclusions

Implications for practice.

From this review, there is insufficient high‐certainty evidence to determine whether or not compression hosiery or stockings are effective in the sole and initial treatment of varicose veins without healed or active venous ulceration, or whether any type of stockings is superior to any other type. Many studies used different outcomes and ways to assess and report their outcomes. Where symptoms were assessed, many studies appeared to show a subjective improvement in participants wearing stockings, but these assessments were not made by comparing one randomised arm of a trial with a control arm, and therefore are subject to bias. To provide evidence as to whether compression stockings are effective in the initial treatment and management of varicose veins in people without healed or active venous ulceration, a large‐scale RCT is needed. Until this is done, no evidence‐based implications for practice can be made.

We found no severe or long‐lasting side effects. However, stockings can have adverse effects if incorrectly applied or used in people with peripheral vascular disease, and those fitting them should have received appropriate training.

Compliance varied between studies depending on types of participants and whether stockings were compared with placebo stockings or a different stocking. Some reasons provided for non‐compliance included discomfort, application, appearance, not being effective and causing irritation.

Comfort, tolerance and acceptability of stockings was affected by the study population. Compression tights were increasingly rejected by pregnant women when their pregnancy progressed, while in one study of non‐pregnant women, the stockings group showed no more hindrance of normal activities and daytime discomfort when compared with placebo stockings. Discomfort was the main reason for indicating a preference for one type of stocking over another.

Implications for research.

During this review, we found no high‐certainty evidence assessing the effectiveness of compression hosiery or stockings in treating varicose veins compared to a control group (either with no treatment or with a placebo or non‐compression stockings). This made it difficult to answer the specific research question. Many of the included studies compared pressures or makes of stocking, which therefore assumes that some type of improvement will be found in wearing stockings. Studies comparing stockings with placebo or no stockings appeared to show a subjective improvement in participants wearing stockings but many of these assessments were not made by comparing one randomised arm of a trial with a control arm, and therefore are subject to bias. A large scale, high‐quality randomised controlled trial is required on this topic.

The reporting of the older included studies is insufficient. While the more recent studies are of higher methodological quality, future research in this subject area should continue to use up‐to‐date reporting guidelines such as CONSORT.

If significant evidence is found that suggests compression stockings are effective in the initial treatment and management of varicose veins in people without healed or active venous ulceration, trials into which is the optimum pressure and length of stocking to use would help guide clinical practice. It may also help standardise the classification of compression hosiery, making provision of stockings easier for healthcare professionals.

What's new

Date	Event	Description
13 April 2021	New search has been performed	New search run. Six new included studies, 36 new excluded studies and five new ongoing studies identified.
13 April 2021	New citation required but conclusions have not changed	New search run. Six new included studies, 36 new excluded studies and five new ongoing studies identified. Review updated incorporating current Cochrane standards including summary of findings tables. No change to conclusions.

History

Protocol first published: Issue 11, 2010
Review first published: Issue 11, 2011

Date	Event	Description
14 October 2013	New citation required but conclusions have not changed	Searches rerun, one new excluded study identified. Review updated accordingly, minor copy edits made. Conclusions not changed
14 October 2013	New search has been performed	Searches rerun, one new excluded study.

Appendices

Appendix 1. Database searches July 2018 and May 2020

Source	Search strategy	Hits retrieved
Vascular Specialised Register in CRSW	#1 VVEINS AND INREGISTER #2 Bandages OR stocking* or hosier* or tight* or sock* AND INREGISTER #3 #1 AND #2	9 July 2018 – 95 12 May 2020 – 25
CENTRAL via CRSO	#1 MESH DESCRIPTOR Varicose Veins EXPLODE ALL TREES 993 #2 varicos*:TI,AB,KY 1646 #3 (tortu* near3 (vein* or veno* or saphenous)):TI,AB,KY 11 #4 (incomp* near3 (vein* or veno* or saphenous or valv*)):TI,AB,KY 110 #5 ((insuffic* near3 (vein* or veno* or saphenous)) ):TI,AB,KY 175 #6 ((saphenous or vein* or veno*) near3 reflux):TI,AB,KY 180 #7 (dilated near3 (vein* or veno* or saphenous)):TI,AB,KY 25 #8 MESH DESCRIPTOR Saphenous Vein EXPLODE ALL TREES 641 #9 GSV:TI,AB,KY 165 #10 MESH DESCRIPTOR Venous Insufficiency EXPLODE ALL TREES 502 #11 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 2587 #12 MESH DESCRIPTOR Bandages EXPLODE ALL TREES 2468 #13 (stocking* or hosier* or tight* or sock* or bandag*):TI,AB,KY 6625 #14 (jobst or surepress or activa or kendall or elbeo or levante or lloveras or cette or sigvaris or solidea or medilast or VenoTrain* or Soleg* or Ulcertec or ComfortPro or Comfort‐Pro or "Ulcer Kit"):TI,AB,KY 249 #15 #12 OR #13 OR #14 7351 #16 #11 AND #15 467 #17 01/01/2013 TO 09/07/2018:CD 611428 #18 #16 AND #17 177	9 July 2018 – 177 12 May 2020 – 201
ClinicalTrials.gov	Varicose Veins OR Saphenous Vein OR GSV OR Venous Insufficiency | Bandages OR stocking* or hosier* or tight* or sock* | Start date on or after 01/01/2013 | Last update posted on or before 07/09/2018	9 July 2018 – 15 12 May 2020 – 5
ICTRP Search Portal	Varicose Veins OR Saphenous Vein OR GSV OR Venous Insufficiency | Bandages OR stocking* or hosier* or tight* or sock*	9 July 2018 – 29 12 May 2020 – ICTRP not available
MEDLINE	1 exp Varicose Veins/ 17150 2 varicos*.ti,ab. 14942 3 (tortu* adj3 (vein* or veno* or saphenous)).ti,ab. 374 4 (incomp* adj3 (vein* or veno* or saphenous or valv*)).ti,ab. 2724 5 (insuffic* adj3 (vein* or veno* or saphenous)).ti,ab. 5242 6 ((saphenous or vein* or veno*) adj3 reflux).ti,ab. 1680 7 (dilated adj3 (vein* or veno* or saphenous)).ti,ab. 1373 8 exp Saphenous Vein/ 14663 9 GSV.ti,ab. 819 10 exp Venous Insufficiency/ 7053 11 or/1‐10 47151 12 exp BANDAGES/ 22900 13 (stocking* or hosier* or tight* or sock* or bandag*).ti,ab. 130279 14 (jobst or surepress or activa or kendall or elbeo or levante or lloveras or cette or sigvaris or solidea or medilast or VenoTrain* or Soleg* or Ulcertec or ComfortPro or Comfort‐Pro or "Ulcer Kit").ti,ab. 3802 15 or/12‐14 153216 16 11 and 15 2874 17 randomized controlled trial.pt. 463484 18 controlled clinical trial.pt. 92483 19 randomized.ab. 415175 20 placebo.ab. 189976 21 drug therapy.fs. 2027760 22 randomly.ab. 293120 23 trial.ab. 431896 24 groups.ab. 1809483 25 or/17‐24 4231736 26 exp animals/ not humans.sh. 4470577 27 25 not 26 3658060 28 16 and 27 821 29 exp animals/ not humans.sh. 4470577 30 28 not 29 821 31 (2016* or 2017* or 2018* or 2012* or 2013* or 2014* or 2015*).ed. 6359789 32 30 and 31 252	9 July 2018 – 252 12 May 2020 – 100
Embase	1 exp varicosis/ 50764 2 varicos*.ti,ab. 17688 3 (tortu* adj3 (vein* or veno* or saphenous)).ti,ab. 587 4 (incomp* adj3 (vein* or veno* or saphenous or valv*)).ti,ab. 3697 5 (insuffic* adj3 (vein* or veno* or saphenous)).ti,ab. 7786 6 ((saphenous or vein* or veno*) adj3 reflux).ti,ab. 2495 7 (dilated adj3 (vein* or veno* or saphenous)).ti,ab. 1981 8 exp saphenous vein/ 13893 9 GSV.ti,ab. 1250 10 exp vein insufficiency/ 9813 11 or/1‐10 81685 12 exp bandage/ 14238 13 (stocking* or hosier* or tight* or sock* or bandag*).ti,ab. 156566 14 (jobst or surepress or activa or kendall or elbeo or levante or lloveras or cette or sigvaris or solidea or medilast or VenoTrain* or Soleg* or Ulcertec or ComfortPro or Comfort‐Pro or "Ulcer Kit").ti,ab. 2829 15 or/12‐14 170107 16 11 and 15 2571 17 randomized controlled trial/ 508736 18 controlled clinical trial/ 460046 19 random$.ti,ab. 1316807 20 randomization/ 78591 21 intermethod comparison/ 236899 22 placebo.ti,ab. 274608 23 (compare or compared or comparison).ti. 471580 24 ((evaluated or evaluate or evaluating or assessed or assess) and (compare or compared or comparing or comparison)).ab. 1764713 25 (open adj label).ti,ab. 64821 26 ((double or single or doubly or singly) adj (blind or blinded or blindly)).ti,ab. 209872 27 double blind procedure/ 151488 28 parallel group$1.ti,ab. 21907 29 (crossover or cross over).ti,ab. 93369 30 ((assign$ or match or matched or allocation) adj5 (alternate or group$1 or intervention$1 or patient$1 or subject$1 or participant$1)).ti,ab. 284511 31 (assigned or allocated).ti,ab. 333883 32 (controlled adj7 (study or design or trial)).ti,ab. 296657 33 (volunteer or volunteers).ti,ab. 225255 34 trial.ti. 252457 35 or/17‐34 4059504 36 16 and 35 609 37 (2016* or 2017* or 2018* or 2013* or 2014* or 2015*).em. 31875144 38 36 and 37 589 39 from 38 keep 1‐589 589	9 July 2018 – 589 12 May 2020 – 137
CINAHL	S30 S16 AND S29 S29 S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 S28 MH "Random Assignment" S27 MH "Single‐Blind Studies" or MH "Double‐Blind Studies" or MH "Triple‐Blind Studies" S26 MH "Crossover Design" S25 MH "Factorial Design" S24 MH "Placebos" S23 MH "Clinical Trials" S22 TX "multi‐centre study" OR "multi‐center study" OR "multicentre study" OR "multicenter study" OR "multi‐site study" S21 TX crossover OR "cross‐over" S20 AB placebo* S19 TX random* S18 TX trial* S17 TX "latin square" S16 S11 AND S15 S15 S12 OR S13 OR S14 S14 TX stocking* or hosier* or tight* or sock* or bandag* S13 TX jobst or surepress or activa or kendall or elbeo or levante or lloveras or cette or sigvaris or solidea or medilast or VenoTrain* or Soleg* or Ulcertec or ComfortPro or Comfort‐Pro or "Ulcer Kit" S12 MH "Bandages and Dressings+" S11 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 S10 MH "Venous Insufficiency+" S9 TX GSV S8 MH "Saphenous Vein" S7 TX (dilated n3 (vein* or veno* or saphenous)) S6 TX ((saphenous or vein* or veno*) n3 reflux) S5 TX (insuffic* n3 (vein* or veno* or saphenous)) S4 TX varicos* S3 TX (incomp* n3 (vein* or veno* or saphenous or valv*)) S2 TX (tortu* n3 (vein* or veno* or saphenous)) S1 MH "Varicose Veins+"	9 July 2018 – 53 12 May 2020 – 40
AMED	1 exp Varicose veins/ 67 2 varicos*.ti,ab. 44 3 (tortu* adj3 (vein* or veno* or saphenous)).ti,ab. 0 4 (insuffic* adj3 (vein* or veno* or saphenous)).ti,ab. 44 5 ((saphenous or vein* or veno*) adj3 reflux).ti,ab. 1 6 (dilated adj3 (vein* or veno* or saphenous)).ti,ab. 0 7 "Saphenous Vein".ti,ab. 19 8 GSV.ti,ab. 1 9 exp Venous insufficiency/ 51 10 (incomp* adj3 (vein* or veno* or saphenous or valv*)).ti,ab. 1 11 or/1‐10 174 12 exp Bandages/ 604 13 (stocking* or hosier* or tight* or sock* or bandag*).ti,ab. 988 14 (jobst or surepress or activa or kendall or elbeo or levante or lloveras or cette or sigvaris or solidea or medilast or VenoTrain* or Soleg* or Ulcertec or ComfortPro or Comfort‐Pro or "Ulcer Kit").ti,ab. 28 15 or/12‐14 1524 16 11 and 15 15 17 exp CLINICAL TRIALS/ 3749 18 RANDOM ALLOCATION/ 314 19 DOUBLE BLIND METHOD/ 657 20 Clinical trial.pt. 1211 21 (clinic* adj trial*).tw. 5381 22 ((singl* or doubl* or trebl* or tripl*) adj (blind* or mask*)).tw. 2833 23 PLACEBOS/ 586 24 placebo*.tw. 3102 25 random*.tw. 17520 26 PROSPECTIVE STUDIES/ 1097 27 or/17‐26 22515 28 16 and 27 3 29 ("2017" or "2018" or "2013" or "2014" or "2015" or "2016").yr. 45367 30 28 and 29 2 31 from 30 keep 1‐2 2	9 July 2018 – 2 12 May 2020 – 0

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Anderson 1990.

Study characteristics
Methods	Prospective, randomised, cross‐over trial with a factorial design. Method of randomisation: not stated. Concealment of allocation: not stated. Details of blinding: not stated. No intention‐to‐treat analysis or sample size calculation provided. Exclusions after randomisation: 6.
Participants	Country: Glasgow, UK. Setting: Glasgow Royal Infirmary (for initial assessment and data collection). Number of participants: 72 randomised. Aged: 20–61 years (mean 40 years). Sex: both. Inclusion criteria: all patients on the waiting list for varicose vein surgery, who were interviewed to determine the presence of lower limb pain, heaviness, itching, night cramps, swelling or cosmetic distress. Patients had to have ≥ 2 of these symptoms (excluding cosmetic distress). Exclusion criteria: only complaint was embarrassment from vein appearance; aged over 65 years; clinical evidence of PAD; concurrent treatment with diuretic, calcium antagonist, non‐steroidal anti‐inflammatory drug, vasodilator or corticosteroid drugs; history of DVT.
Interventions	4 treatments: placebo capsules alone; oxerutins (Paroven) alone; hosiery + placebo; hosiery + oxerutins (paroven). Oxerutins (Paroven): 250 mg 4 times a day for 28 days. Hosiery: full length and fitted to give a pressure of 30–40 mmHg at the ankle. Control: each participant acted as their own control. Placebo was also used. Duration: each treatment was taken for successive 4‐week periods and treatment sequence was balanced within groups of 12 in 3 Latin squares to minimise carry‐over effect. We used the comparison of stocking + placebo vs placebo alone.
Outcomes	Primary outcome: subjective symptoms, including pain, heaviness, itching, swelling and cramp measured by VAS following each treatment. Secondary outcomes: compliance assessed by counting the number of capsules left at each return visit and by asking the participant how long they wore the stockings for each day. Aim of study: to assess efficacy of graduated compression hosiery and oxerutins (paroven), both singly and in combination, when treating varicose veins.
Funding	Acknowledgements to "Zyma (UK) Ltd and Ganzoni (Switzerland) for providing Paroven and placebo capsules and Sigvaris 503 graduated compression hosiery."
Declarations of interest	Not reported.
Notes	No washout period between treatments but study authors reported treatment sequence was balanced within groups of 12 in 3 Latin squares to minimise carry‐over effect.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Treatment sequence was balanced within groups of 12 in 3 Latin squares to minimise carry‐over effect. No further information provided.
Allocation concealment (selection bias)	Unclear risk	Insufficient information provided.
Blinding of participants and personnel (performance bias)	Unclear risk	Insufficient information provided although participants will have known if they were provided with a stocking.
Blinding of outcome assessment (detection bias)	Unclear risk	No information on whether outcome assessors were blinded to treatment arms.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	All drop‐outs/withdrawals accounted for, but unclear when reporting clinic attendance.
Selective reporting (reporting bias)	Unclear risk	Primary outcome reported. Little information or analyses on compliance.
Other bias	Unclear risk	No washout periods given between treatments although treatment sequence was balanced within groups of 12 in 3 Latin squares to minimise carry‐over effect.

Cazaubon 2013.

Study characteristics
Methods	Single‐centre open randomised cross‐over controlled trial. Method of randomisation: randomisation list. Concealment of allocation: randomised by CENBIOTECH for Pierre Fabre Sante laboratories. The stockings were delivered according to the randomisation list (progressive or degressive) provided to the investigator, according to the order of inclusion of the participants. Details of blinding: no blinding. Sample size calculation was provided: a target of 10 participants per study arm was required at risk alpha = 0.05 to compare the diameter of the venous structures with an estimated difference of ≥ 2 mm, an estimated variance of the difference in 2.5 and a power of 90% in a cross‐over equivalence test. Exclusions after randomisation: none.
Participants	Country: France. Setting: clinic. Number of participants: 20. Age: mean 52.9 (SD 16.8) years. Sex: 17 women, 3 men. Inclusion criteria: men and women aged > 18 years; provided written informed consent; affiliated to or part of the French social security system; complied with study; had chronic venous disease C2 (varices) or C3 (oedema) according to the CEAP classification. Exclusion criteria: currently participating or having participated in the previous 3 months in another therapeutic trial or undergone treatment in the previous 15 days by elastic or inelastic compression, whether bandage, suture, stocking or tights; unilateral oedema and post‐thrombotic syndrome; poorly controlled diabetes; BMI > 30; symptomatic or asymptomatic obliterating arteriopathy of the lower limbs, characterised by a distal systolic pressure index < 0.7; lymphoedema; language or psychological disability to provide informed consent; documented history DVT.
Interventions	Treatments: progressive compression stocking, knee length (Progressive N'System) or degressive compression stocking, knee length (Class III Veinostim). Duration: 120 minutes.
Outcomes	Primary outcome: change in diameter of deep and superficial veins. Secondary outcomes: change in venous reflux (amplitude and duration), difficulties donning stockings, exerted pressures during use of stockings.
Funding	Funding not specifically reported but randomisation done on behalf of Pierre Fabre Laboratories and 1 author was staff of Pierre Fabre Laboratories.
Declarations of interest	Not stated.
Notes	Washout: 30 minutes following by walking 100 m.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomised by CENBIOTECH for Pierre Fabre Sante laboratories. The stockings were delivered according to the randomisation list (progressive or degressive) provided to the investigator, according to the order of inclusion of the participants.
Allocation concealment (selection bias)	Low risk	Randomised by CENBIOTECH for Pierre Fabre Sante laboratories. The stockings were delivered according to the randomisation list (progressive or degressive) provided to the investigator, according to the order of inclusion of the participants.
Blinding of participants and personnel (performance bias)	High risk	Open, non‐blinded cross‐over trial.
Blinding of outcome assessment (detection bias)	High risk	Open, non‐blinded cross‐over trial.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Some baseline measures not available for all participants. Unclear if this is the same for the follow‐up measurements. Power calculations provided.
Selective reporting (reporting bias)	Low risk	All relevant outcomes presented.
Other bias	Low risk	No evidence of other bias.

Chant 1985.

Study characteristics
Methods	Randomised controlled trial. Method of randomisation: participants were selected sequentially from a surgical waiting list, no further information provided. Method of concealment: not stated. Details of blinding: results were "reviewed blind," no information on whether participants or other personnel were blinded. No power calculation or intention‐to‐treat analysis provided. Exclusions after randomisation: 163 people initially asked to take part, but 104 actually entered the trial and were randomised. Quote: "25 did not reply because they had moved from the area, 4 had undergone operations elsewhere and 30 declined to participate."
Participants	Country: Southampton, UK. Setting: Department of Vascular Surgery. No: 104 participants. Age: not stated. Sex: not stated. Inclusion and exclusion criteria: no clear criteria stated. Quote: "Groups were evenly matched for age, symptomatology, and extent of varicose veins." Patients were selected from a varicose vein surgical waiting list (quote), "starting with those added most recently."
Interventions	Treatments: 53 participants to wear below‐knee stockings providing 30–40 mmHg pressure at the ankle or 51 participants to wear below‐knee stockings providing 40–50 mmHg pressure at the ankle. Control: not stated. Duration: 6 weeks.
Outcomes	Primary outcome: leg symptoms (self‐reported). Secondary outcome: tolerance of the stocking. Aim of study: to investigate the acceptability of the stocking (Sigvaris). When reviewed (quote) "particular attention was paid to tolerance of the stockings and whether symptoms were better, worse or unchanged."
Funding	Sigvaris Company provided the stockings.
Declarations of interest	Not reported.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were selected sequentially from a surgical waiting list." No information on how the sequence was generated was provided.
Allocation concealment (selection bias)	Unclear risk	Insufficient information provided.
Blinding of participants and personnel (performance bias)	Unclear risk	No information on whether the participants or personnel other than reviewers were blinded.
Blinding of outcome assessment (detection bias)	Low risk	Reviewers were blinded. Quote: "They were then reviewed blind."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Insufficient information to permit judgement.
Selective reporting (reporting bias)	Unclear risk	The primary outcome of leg symptoms was reported. However, tolerance was not clearly reported. Quote: "Of the 104 patients who took part in the trial, 80 claimed the stockings were comfortable … the main cause of discomfort was not simply that they were too tight." The main focus in the comment section was that they were able to reduce their waiting list by 51 patients, who wanted to be removed from the surgical waiting list due to symptom improvement. This was not an aims or outcomes stated in the methods.
Other bias	Unclear risk	Quote: "we accept that the study was biased towards surgery because patients were taken from the waiting list …"

Chant 1989.

Study characteristics
Methods	Randomised controlled trial. Method of randomisation: not stated. Concealment of allocation: not stated. Details of blinding: none stated. No power calculation and no intention‐to‐treat analysis. Exclusions/loses after randomisation: 26. 22 failed to collect the prescribed stockings. A further 4 underwent elective surgery before having a chance to assess the stocking effects.
Participants	Country: Southampton, UK. Setting: Royal South Hants Hospital outpatient department and participants' homes. Number of participants: 66 randomised. Age: not stated. Sex: not stated. Inclusion criteria: unclear, patients awaiting surgery for varicose veins were included. Exclusion criteria: not stated.
Interventions	Treatments: of those who collected the stockings: 18 participants wore Medi Plus stockings or 22 participants wore Sigvaris stockings. Prescription was tailored to the participants' degree of venous insufficiency as specified in the manufacturer's guidelines. Control: not stated. Duration: not clearly stated. Data were collected (quote) "on average 6 weeks following collection of stockings."
Outcomes	Primary outcome: participant compliance with wearing stockings. Participant's physical ability to put the stockings on.
Funding	Not stated.
Declarations of interest	Not stated.
Notes	No information as to the level of pressure provided by the stockings provided. Participants appeared to have been given varying degrees of compression stocking depending on their symptoms (quote): "The exact prescription was tailored to the patients' degree of venous insufficiency as specified in the manufacturer's guidelines." High withdrawal rate from beginning of the study (39%).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information reported.
Allocation concealment (selection bias)	Unclear risk	Insufficient information reported.
Blinding of participants and personnel (performance bias)	Unclear risk	Insufficient information reported.
Blinding of outcome assessment (detection bias)	Unclear risk	Insufficient information reported.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Reasons provided for all dropouts and no missing outcome data. Results written to allow actual number of participants to be seen and accounted for.
Selective reporting (reporting bias)	Unclear risk	Compliance was reported, but little information regarding grip strength data (Chi²) only. No results given or discussed regarding symptomatic relief.
Other bias	Unclear risk	Pressure of stocking not known, possibly varied depending on individual symptoms/venous insufficiency: quote: "prescription was tailored to the individual." High withdrawal/drop‐out rate.

Chauveau 2000.

Study characteristics
Methods	Randomised cross‐over trial. Method of randomisation: not stated. Concealment of allocation: not stated. Details of blinding: not stated. No information provided regarding intention‐to‐treat analysis or a power calculation. Exclusions after randomisation: none.
Participants	Country: Paris, France. Setting: outpatients at the Phlebology Department of Notre Dame de Bon Secours Hospital, Paris. Number of participants: 10. Age: mean 52 years (range 27–77 years). Sex: all female. Inclusion criteria: mild‐to‐moderate primary varicose veins, with or without skin trophic disorder. Some participants also reported other symptoms: 8 complained of leg heaviness, 4 of leg pain and 3 of night cramps. Exclusion criteria: no clear exclusion criteria stated, but no participants had a history of DVT, sclerotherapy within the last 6 months, clinical evidence of lower limb obstructive arteriopathy, or acute or severe illness. All had normal deep veins.
Interventions	Treatments: French class 1 (10–15 mmHg) below‐knee stockings or French class 2 (15–20 mmHg) below‐knee stockings. Stockings worn by all participants allocated in a random order. Control: measures taken before stockings were worn. Duration: not clear. Study followed a protocol, which included starting at 9 a.m. and wearing each stocking for 15 minutes, between control measures (15 minutes without wearing a stocking).
Outcomes	Primary outcome: calf volume changes (via air plethysmography). Air plethysmography with venous occlusion (50 mmHg) was used to measure AI, venous volume (V50) and MVO.
Funding	Not stated.
Declarations of interest	Not stated.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information provided. Quote: "Each patient was examined with both stocking classes, allocated in a random order."
Allocation concealment (selection bias)	Unclear risk	Insufficient information reported.
Blinding of participants and personnel (performance bias)	Unclear risk	Insufficient information reported.
Blinding of outcome assessment (detection bias)	Unclear risk	Insufficient information reported.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Unclear as results table only gave mean value with SD.
Selective reporting (reporting bias)	Unclear risk	Results reported outcome that MVO was unchanged by class 1 and class 2 below‐knee stockings. Requires further information to permit judgement.
Other bias	Unclear risk	Sample size was small (10 participants). Participants only wore stockings for 15 minutes.

Coughlin 2001.

Study characteristics
Methods	Randomised controlled trial. Method of randomisation: not stated. Concealment of allocation: not stated. Details of blinding: not stated. Participants were obviously aware if they were provided with a stocking or not. No power calculation or intention‐to‐treat analysis. Exclusions/drop‐outs after randomisation: of the 46 randomised to wear tights, an initial 15 opted not to wear them.
Participants	Country: Chester, UK. Setting: antenatal clinic of Countess of Chester Hospital. Number of participants: 83 identified, 46 randomised to wear tights. Age: not stated. Sex: all women (all pregnant). Inclusion criteria: not clearly stated. All were pregnant, diagnosed with superficial reflux from a scan, and had varicose veins and normal deep veins. Exclusion criteria: not stated.
Interventions	Treatment: randomised to wear class 1 compression tights or not. Control: it is presumed those not randomised to wear tights (37 participants) acted as the control, but no further information is given on this group. Duration: not clearly stated. Initial booking visit, up until 6 weeks' postpartum. It is unclear if this was the preidentified time to stop wearing tights or the women just stopped wearing them at this time.
Outcomes	Primary outcome: acceptability and, therefore, compliance/usage of compression tights in pregnant women.
Funding	Not stated.
Declarations of interest	Not stated.
Notes	No information on the classification of the stocking, and therefore the pressure exerted, is provided. High drop‐out rate (32%).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information reported. Quote: "46 women were randomised to wear tights …"
Allocation concealment (selection bias)	Unclear risk	Insufficient information reported.
Blinding of participants and personnel (performance bias)	Unclear risk	Participants were obviously not blinded as they were either given tights or not, but no information given as to whether assessors were blinded.
Blinding of outcome assessment (detection bias)	Unclear risk	No information given as to whether assessors were blinded.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not known where the other 37 possible control women were assessed or not.
Selective reporting (reporting bias)	Unclear risk	Insufficient information reported.
Other bias	Unclear risk	High withdrawal rate at baseline (15 participants, 32%), may make conclusion less robust.

Couzan 2012.

Study characteristics
Methods	Randomised, double‐blind, multi‐centre trial. Method of randomisation: computer‐generated randomisation list (after screening for eligibility). Concealment of allocation: degressive and progressive compressive stockings were identical in appearance, made with the same material, and prepared by the same manufacturer. Details of blinding (quote): "lower limb measurements were automatically sent to the logistic centre of treatment distribution that was in charge of preparing the treatment and sent them directly to the patients using pre‐stamped envelopes. Finally, patients were instructed not to bring their compressive stockings to the evaluation visit. Neither the patient nor the investigator was informed of the assigned group." Sample size calculation provided (quote: "with 80% power, using a two‐tailed test at the 0.05 threshold, 192 patients per group were required, and it was decided to recruit 400 patients overall"). Exclusions after randomisation: 9 participants lost to follow‐up, and 11 had no assessment of the primary outcome.
Participants	Country: France. Setting: outpatients recruited via 44 angiologists throughout France in a multi‐centre study. Number of participants: 401 included and randomised (199 assigned to progressive compression stockings, 202 assigned to degressive compression stockings). Data from 381 participants were available for the primary outcome. Age: progressive stocking group: median 53 (range 43–62 years); degressive stocking group: median 54 (range 42–62 years). Sex (male): progressive stocking group: 54 (27.7%); degressive stocking group: 43 (21.7%). Inclusion criteria: men and women outpatients presenting with current pain or heavy legs (or both) due to moderate‐to‐severe CVI (CEAP C2b–C5) and eligible for 30 mmHg compressive therapy. Exclusion criteria: bandage therapy recommended, current use of compressive stocking > 30 mmHg, active ulcer, DVT or pulmonary embolism in past 3 months, arterial disease of the lower limb, non‐venous oedema, inflammatory dermatological or traumatic disorder of a lower limb, known hypersensitivity to components of the study compressive stockings, surgery or vascular procedure in the past month or planned in the next 3 months, poor life expectancy, inability to walk and pregnancy.
Interventions	Treatments: upward progressive compressive stockings, knee length (10 mmHg at the ankle, 23 mmHg at the upper calf) or degressive compressive stockings, knee length (30 mmHg at the ankle, 21 mmHg at the upper calf). Duration: participants were instructed to wear the compressive stockings daily (from morning to bedtime) for 6 months.
Outcomes	Primary outcome: evaluated after 3 months of treatment, was a composite and defined as an improvement of pain or heavy legs without onset of either ulcer, DVT or SVT of the lower limb, or pulmonary embolism. Improvement of pain and heavy legs were evaluated using the combination of two 4‐level scores with the following categories: disappearance, important amelioration, slight amelioration and lack of amelioration. The improvement was defined as the disappearance or an important amelioration in the  above criteria. Secondary outcomes: these were the primary composite outcome at months 1 and 6, as well as each component of the composite outcome at month 3, compliance, ease of application and discomfort/harm related to the compressive stockings at months 1, 3 and 6. Participants were interviewed concerning eventual venous or adverse events, compliance, easiness to apply and discomfort/harm related to the stockings. At month 3, a physical examination was performed and CEAP and modified VCSS were evaluated.
Funding	Quote: "Laboratoire Pierre Fabre, France, approved the study protocol, provided the stockings, gave an unrestricted grant for the conduct of the study, and was given the opportunity to comment on the manuscript."
Declarations of interest	Quote: "Dr Couzan has patented the progressive stockings and he has shares in BV SPORT Company which holds the patents. Dr Leizorovicz received research funds for the coordination of the study and fees for consultancy for Pierre Fabre. Dr Pouget has shares in BV SPORT Company which hold the patents. Dr Quere received fees for consultancy for Pierre Fabre. Drs Mismetti and Laporte and Mrs Chapelle report no conflict of interest."
Notes	Data/results for the primary outcome were split by 3 CEAP levels (C2b, C3 and C4a to C5).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation performed by computer, measurements sent to logistic centre of treatment distribution.
Allocation concealment (selection bias)	Low risk	Quote: "lower limb measurements sent automatically to the logistic center of treatment distribution that was in charge of preparing the treatment and sent them directly to the patients using pre‐stamped envelopes."
Blinding of participants and personnel (performance bias)	Low risk	Clear description that stockings were identical in appearance (same material and manufacturer). Logistic centre of treatment distribution sent the participants the stockings directly and participants were asked not to bring their stockings to the evaluation centre. Therefore, neither the participant nor the investigator was aware.
Blinding of outcome assessment (detection bias)	Low risk	Clear description that stockings were identical in appearance (same material and manufacturer). Logistic centre of treatment distribution sent the participants the stockings directly and participants were asked not to bring their stockings to the evaluation centre. Therefore, neither the participant nor the investigator was aware.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Figure 1 provides details of participant dropout but unclear as to reasons for attrition/non‐inclusion.
Selective reporting (reporting bias)	Low risk	All outcomes reported via tables and description in the text. However, little explanation on analysis for the secondary outcomes (collected via telephone call to participants).
Other bias	Low risk	No evidence of other bias.

Heidarimoghadam 2020.

Study characteristics
Methods	Randomised controlled trial. Method of randomisation: simple random sampling method. Concealment of allocation: no information provided. Details of blinding: no information provided. However, authors stated that the intervention group wore stockings and only this group were sent stockings. The control group did not wear stockings. Suggesting both participants and personnel were aware of which group they were in. No information provided on the intention to treat or a power calculation. Exclusions after randomisation: not stated.
Participants	Country: city of Hamadan, Iran. Setting: hairdressers who had been referred to Mahdieh Clinic and diagnosed by a physician. Participants were asked to wear their stockings while at work. Using simple random sampling method, 70 people were selected out of the hairdressers who had varicose veins. Number of participants: 70. Age: intervention group: mean 43.22 (SD 8.77); control group: mean 44.17 (SD 10.31). Sex: women. Inclusion criteria: diagnosed by physicians to have varicose veins, women, working as a hairdresser. Exclusion criteria: not stated.
Interventions	Treatment: intervention group were asked to wear compression stockings (ADOR, Faraz Gostar Farham co, Iran) during work only. Stockings were of AD size which covered feet and lower legs. Control: no intervention/stockings. Duration: 3 months.
Outcomes	Primary outcomes: quality of working life associated with varicose veins measured using 3 indices of varicose veins, chronic pain and muscle fatigue. Data collection instruments included demographic properties questionnaire, AVVQ, CPGS and MFQ in lower extremities.
Funding	None stated.
Declarations of interest	Quote: "None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission."
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "… were selected through simple random sampling method …"
Allocation concealment (selection bias)	Unclear risk	No information provided.
Blinding of participants and personnel (performance bias)	High risk	No report of blinding of participants or personnel. No information provided on blinding – participants were asked to wear the stockings (either intervention or control) but no information as to whether or not they were blinded or whether study personnel were blinded. The study authors stated that the intervention group wore stockings and only this group were sent stockings. The control group did not wear stockings. Suggesting both participants and personnel were aware.
Blinding of outcome assessment (detection bias)	Unclear risk	The study paper inferred that participants in the intervention group were sent their stockings – but it was not clear who sent them – study personnel/outcome assessors, or someone else. No clear report.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Study authors reported all participants completed the study.
Selective reporting (reporting bias)	Unclear risk	The data provided in the results was unclear as to whether or not it related to all the stated questionnaires in the methods.
Other bias	Low risk	No evidence of other bias.

Jones 1980.

Study characteristics
Methods	Randomised cross‐over trial. Method of randomisation: not stated. Concealment of allocation: not stated. Details of blinding: not stated. No power calculation or intention‐to‐treat. Exclusions after randomisation: none.
Participants	Country: London, UK. Setting: Thrombosis Research Unit, King's College Hospital. Number of participants: 30 (in 3 groups, 1 being varicose veins with 10 participants). Age: not stated. Sex: 26 female, 4 male. Inclusion criteria: group 1: normal deep veins and no varicose veins (10 female); group 2: superficial varicose veins (9 female, 1 male); group 3: postphlebitic limb (7 female, 3 male). Exclusion criteria: not stated.
Interventions	Treatment: participants wore Eesiness NHS 2‐way stretch stockings (20 mmHg) or Sigvaris graduated pressure stockings (30–40 mmHg) in a random order. Control: the 30 participants all had control measures taken at the initial visit via foot volumetry and sodium clearance. Group 1 were also used as a control group, but were recruited after a suspected DVT or aching legs. Duration: 3 weeks with 1 stocking, 1 week with no stocking, then 3 weeks with the other stocking.
Outcomes	Primary outcome: competence of superficial and deep venous system measured by foot volumetry (EV, EVR, Q, Q/EVR and T1/2) and sodium subcutaneous tissue clearance. Secondary outcome: patient acceptability of stockings.
Funding	Acknowledgements given to Ganzoni and Cie AG, St Gallen, Switzerland for supplying the Sigvaris stockings. Quote: "This work has been supported by MRC Programme Grant No.G973/756."
Declarations of interest	Not stated.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information reported.
Allocation concealment (selection bias)	Unclear risk	Insufficient information reported.
Blinding of participants and personnel (performance bias)	Unclear risk	No mention of whether measures were in place to blind participants from the type of stocking they were wearing.
Blinding of outcome assessment (detection bias)	Unclear risk	No mention of whether assessors were blinded to type of stocking when collecting or analysing data.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No missing data obvious, but results given as means and SDs.
Selective reporting (reporting bias)	Unclear risk	Insufficient information reported.
Other bias	Unclear risk	Small number of participants with varicose veins (10).

Jungbeck 1997.

Study characteristics
Methods	Randomised controlled trial. Method of randomisation: not stated. Concealment of allocation: not stated. Details of blinding: not stated. No power calculation or intention‐to‐treat analysis. Exclusions after randomisation: 6 withdrew from the study.
Participants	Country: Lund, Sweden. Setting: Department of Vascular Surgery and Vascular Laboratory, University Hospital, Lund. Number of participants: 37. Age: range 27–82 years. Sex: 21 women, 9 men. Inclusion criteria: seeking advice for symptomatic varicose veins with (or without) minor skin changes. Patients could have bilateral venous insufficiency, classified as grade 2 (varicose veins) and recurrent varicose veins. Exclusion criteria: not stated.
Interventions	Treatment: low grade (class 1, 20 mmHg) or medium grade (class 2, 30 mmHg) Jobst Medical Leg wear knee‐high graduated stockings. Control: none stated. Baseline values of foot volumetry taken. Duration: 8 weeks.
Outcomes	Primary outcomes: foot volumetry measures (EV, EVrel, Q and Q/EVrel) and VAS used to evaluate pain, ankle swelling, tired legs, restless legs and night cramps according to the participants. VAS was repeated after the 8 weeks of compression treatment.
Funding	Quote: "The supply of stockings and the contribution by Beiersdorf AG, Germany, is greatly appreciated."
Declarations of interest	Not stated.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Insufficient information reported.
Allocation concealment (selection bias)	Unclear risk	Insufficient information reported.
Blinding of participants and personnel (performance bias)	Unclear risk	Insufficient information reported.
Blinding of outcome assessment (detection bias)	Unclear risk	Insufficient information reported.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No missing data stated, but unclear as results given as percentages.
Selective reporting (reporting bias)	Unclear risk	Foot volumetry outcomes reported. However, VAS results were expressed as median percentages for each class of stocking, making it impossible to distinguish differences in individual symptoms.
Other bias	Low risk	No evidence of other bias.

Kakkos 2018.

Study characteristics
Methods	Multi‐centre, randomised, double‐blind, placebo‐controlled trial. Method of randomisation: on agreement to participate in the trial (signed informed consent), randomisation performed using sequentially numbered, sealed, opaque envelopes that contained a paper slip showing the randomisation group. The parallel group trial had a 1:1 allocation ratio. Concealment of allocation: a member of the group who was unaware of the clinical characteristics of the participants handled all randomisation envelopes and notified the manufacturer's local distributor by sending the randomisation group, leg measurements required to fit the stockings and participant's address. A pair of active or placebo GECS was sent by courier to the participant the same or the next day. Details of blinding: randomisation group was not communicated to the patient or the outcome assessors. To guarantee blinding of participants and outcome assessors for performance bias and detection bias, respectively, all stocking labels were removed by the manufacturer's local distributor before shipping, so that the 2 stocking types looked similar. Additionally, all participants were instructed to remove their stocking and conceal them from the outcome assessors at the time of their follow‐up. Sample size calculation was provided: used a priori power calculations based on a previous study in which a mean VAS of 4.5/10 before use of Class 1 (20 mmHg) GECS was reduced to 1.5/10 afterwards. Assuming a reduction of a mean VAS of 4.5/10 to 3.5/10 using a PS, and also an SD of 1.5 for the 2 groups, a total of 24 participants (12 in each group) would be required to demonstrate statistical significance (α = 0.05) at a power of 90%. To compensate for possible losses to follow‐up or participant withdrawal from the study, they included 30 patients (15 in each group). Exclusions after randomisation: 2 participants discontinued intervention; 1 from each group due to consent withdrawal.
Participants	Country: Patras, Greece. Setting: vascular outpatient clinics of the University Hospital and the vascular outpatient clinic of a primary care provider. Number of participants: 30 included and randomised (15 per group). Data from 14 patients in each group were analysed. Age: PS: mean 53.7 (SD 11.2) years; Class 1 stockings: mean 52.9 (SD 13.2) years. Sex: both genders, PS: 1 male, 14 females; Class 1 stockings: 1 male, 14 females Inclusion criteria: primary varicose veins causing pain/aching located only at calf level in participants of both genders aged 18–90 years. Exclusion criteria: venous ulceration, venous eczema, itching, SVT, PAD (intermittent claudication, critical limb ischaemia or a vascular intervention), symptoms not of venous origin, and previous use of elastic stockings.
Interventions	Treatment: graduated elastic stockings VARISAN TOP, off‐the‐shelf knee‐length Class 1 (18–21 mmHg, RAL certified, at the ankle) (Cizeta Medicali S.p.A, Cuggiono, MI, Italy). Control: knee‐length VARISAN diabetic (0 mmHg at the ankle level; Cizeta Medicali). Duration: 1 week.
Outcomes	Primary outcome: dull pain or aching graded by the participant using a VAS (1–10 at baseline) of the leg with the varicose veins. For bilateral varicose veins, the leg with the highest VAS score was considered the index leg. Secondary outcomes: leg symptoms of heaviness, swelling sensation, varicose vein throbbing, burning sensation, paraesthesiae, night cramps and restless legs, and insomnia, considered to be a secondary symptom caused by the leg symptoms, all graded with VAS (0–10). In cases of bilateral varicose veins, the same outcome measures of the index leg were assessed for the contralateral leg, all graded similarly with VAS (0–10). Other secondary outcomes included a modified version of the revised Venous Clinical Severity Score (rVCSS‐S), which did not account for the attribute of compression, and ankle circumference (in cm) measured just above the malleolus, at the smallest point, both for the index and contralateral (if applicable) leg. All outcomes were recorded at baseline and after 1 week of stocking use.
Funding	Quote: "The study was partially funded by VICAN‐ N. Anagnostakis S.A, Athens, Greece. The funder provided the 2 types of stockings used in the trial with no other involvement."
Declarations of interest	Study paper reported no conflicts of interest.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Sequentially numbered, sealed, opaque envelopes that contained a paper slip showing the randomisation group", "This parallel group trial had a 1:1 allocation ratio," "a member of the group who was unaware of the clinical characteristics of the patients handled all randomisation envelopes."
Allocation concealment (selection bias)	Low risk	Quote: "Sequentially numbered, sealed, opaque envelopes that contained a paper slip showing the randomisation group", "This parallel group trial had a 1:1 allocation ratio," "a member of the group who was unaware of the clinical characteristics of the patients handled all randomisation envelopes."
Blinding of participants and personnel (performance bias)	Low risk	Randomisation was sent to the manufacturer who provided the passive or active stockings to the participant via courier directly. Randomisation was not communicated to the participant or the outcome assessor. All stocking labels were removed by the distributor prior to sending, and participants were instructed to remove their stockings before their follow‐up appointment by the outcome assessor.
Blinding of outcome assessment (detection bias)	Low risk	Randomisation was sent to the manufacturer who provided the passive or active stockings to the participant via courier directly. Randomisation was not communicated to the participant or the outcome assessor. All stocking labels were removed by the distributor prior to sending, and participants were instructed to remove their stockings before their follow‐up appointment by the outcome assessor.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Full details of power calculation provided with full CONSORT flow chart. All dropouts accounted for.
Selective reporting (reporting bias)	Low risk	All planned outcomes as reported in methods sections and in ClinicalTrials.gov record reported on.
Other bias	Unclear risk	Underpowered for most symptoms other than pain/aching.

Mariani 2013.

Study characteristics
Methods	Randomised, placebo‐controlled clinical trial. Method of randomisation: sealed envelope technique. Concealment of allocation: no further details other than sealed envelope technique of randomisation stated. Details of blinding: no further details other than sealed envelope technique of randomisation stated. Sample size calculation was not provided. Exclusions after randomisation: 4 participants were excluded within the first 3 days after randomisation, all in the compression stocking group. The participants were unwilling to continue as donning of the compression stocking was too difficult.
Participants	Country: Italy. Setting: Vascular Surgery Unit, Valdisieve Clinic. Number of participants: 60; randomisation (and enrolment) stopped once 60 participants had been enrolled. Participants were randomised into 2 groups; placebo and compression stocking. 4 participants (all in the compression stocking group) were excluded after randomisation, therefore, data for 56 participants were obtained). Age: compression stocking group: mean 62.38 (SD 14.00) years; PS group: mean 65.20 (SD 15.33) years. Sex: compression stocking group: 13 men (50%), 13 women (50%); PS group: 10 men (33.3%), 20 women (66.7%). Inclusion criteria: men and women aged 18–90 years; with unilateral or bilateral CVI CEAP C3 both at screening (V1) and baseline visit (V2) assessed by clinical examination and duplex sonography; presence of chronic, pitting oedema at a stable stage; no effective compression treatment performed so far; ability and willingness to follow the protocol. Exclusion criteria: aged < 18 or > 90 years; refused consent; effective compression therapy started before presentation; disease/symptoms that imitate the symptomatology of CVI (i.e. cardiac, hepatic, renal, orthopaedic or other cause of leg oedema); manifest cardiac insufficiency (stage NYHA III or IV); diabetes mellitus (type I or II); severe renal insufficiency; severe hepatic insufficiency; hypoalbuminaemia; arterial insufficiency or neuropathy of diabetic or other origin; hypertension in therapy with calcium antagonists; acute DVT/SVT; acute ulceration; lymphoedema; pregnancy; lipoedema; severe obesity (BMI > 40); active malignant disease; life expectancy < 90 days.
Interventions	Treatment: class II below‐knee compression stockings MCS (BSN medical‐ Jobst UltraSheer RAL, pressure at the ankle 23–32 mmHg). Control: PS with pressure at the ankle 3–6 mmHg. Duration: 7 days (1 week). Stockings were used during the day and removed during the night for 1 week.
Outcomes	Primary outcome: reduction of oedema assessed by the measure with duplex scan sonography (probe 6–10 mHz) of the thickness of the subcutaneous tissue with the presence of oedema at the ankle (point B1) and the calf (point C), limb measurements at point B1 and C of the leg and by independent comparison of metered photographs taken at the beginning and the end of the trial phase which was 1 week (oedema measured in cm of circumferences at the point B1 and C of the limb). Secondary outcomes: practicability of use of the MCS compared with the PS, including: treatment time to reduce oedema; comfort/discomfort, assessment of tolerability (VAS and modified Venkatraman questionnaire); patients' mobility (score).
Funding	Not stated.
Declarations of interest	Not stated.
Notes	All participants were CEAP C3.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "… randomized in two groups to wear MCS or PS." Comment: no further information provided.
Allocation concealment (selection bias)	Low risk	Quote: "sealed envelope technique."
Blinding of participants and personnel (performance bias)	Unclear risk	Study used PS as control intervention. Unclear if PS was identical to compression stocking and if participants and personnel were blinded.
Blinding of outcome assessment (detection bias)	Unclear risk	No clear information on how this was undertaken – no mention of blinding of outcome assessors.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All participants accounted for; 60 initially recruited with 4 dropouts; 4 participants excluded within first 3 days after randomisation (all in MCS group) as unwilling to continue due to difficulties donning the stockings. All other participants completed the study.
Selective reporting (reporting bias)	Unclear risk	Participant's mobility (reported as a score) was noted as a secondary endpoint within the paper. However, there were no scores associated with mobility in the results section. There was 1 comment noting (quote) "The patients’ mental state, joint mobility and activity (measured with the Norton scale) were very good for all patients in both groups." Hence, reporting was unclear on this outcome.
Other bias	Low risk	No evidence of other bias.

Riebe 2018.

Study characteristics
Methods	Prospective, open randomised, double‐blind, controlled cross‐over trial. Method of randomisation: computer‐generated randomisation list (RStudio). Concealment of allocation: computer‐generated randomisation list performed by an independent statistician. Details of blinding: stockings handed out to participants by a person who was not involved into examination and evaluation. Every participant put on the stocking and interface pressure measured independently by a person not involved in the other measuring routine. Stockings resembled each other in appearance. Sample size calculation provided (for a significance level of 5% and a power of 80%, a cohort size 32 participants was required). Exclusions after randomisation: none.
Participants	Country: Greifswald, Germany. Setting: Department of Dermatology, University of Greifswald. Healthy volunteers recruited from Greifswald by notice. Number of participants: 66 enrolled, 64 randomised (quote: "two subjects were excluded before starting the wear period due to incompliance"). Age: healthy volunteers: median 26 years, range 21–50 years; participants with CVI: median 49.5 years, range 23–81. Sex: healthy volunteers: men 13, women 19; participants with CVI: men 6, women 26. Inclusion criteria: adults aged ≥ 18 years with unrestricted mobility, CVI in clinical stages CEAP C3–C4 (for participants with CVI). For healthy volunteers, a physiological venous blood flow was required. Exclusion criteria: diseases associated with a tendency for oedema, medication with possible influence on leg oedema, diabetes mellitus, uncompensated heart failure, PAD with ABI < 0.8, cerebrovascular diseases, non‐compliance. Trial participants were divided into 2 investigation groups: healthy volunteers and people with CVI.
Interventions	Treatment 1: knee length GECS (RAL Reichs‐Ausschuss für Lieferbedingungen, Sankt Augustin, Germany. Compression class II, 23–32 mmHg, maximal interface pressure exerted at area of the ankle with a declining pressure from distal to proximal). Treatment 2: knee length progressive elastic compression stockings (maximal interface pressure (23–32 mmHg) exerted over the maximal calf circumference). Duration: 3 weeks (1 week of treatment, a 1 week break, 1 week of treatment). Stockings were worn for ≥ 8 hours per day (documented in a diary) not during the night.
Outcomes	Primary outcome: volume reduction (measured in 2 lower leg segments: lower leg (knee to ankle) and distal lower leg and foot (midst of lower leg to the toes)). Secondary outcomes: assessment of clinical symptoms by means of VCSS for participants with CVI and the evaluation of side effects and wear comfort in both investigation groups; interface pressure, ejection fraction and venous filling index.
Funding	Quote: "Bauerfeind (Zeulenroda, Germany) provided the compression stockings."
Declarations of interest	Authors reported no potential conflicts of interest.
Notes	Washout: 1 week break between 2 treatment periods. We presented data for the investigation group of participants with CVI only.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation list performed by an independent statistician using (quote) "free software 'RStudio' with is r‐package blockrand (RStudio Inc., Boston, USA)."
Allocation concealment (selection bias)	Low risk	Computer‐generated randomisation list performed by an independent statistician using (quote) "free software 'RStudio' with is r‐package blockrand (RStudio Inc., Boston, USA)."
Blinding of participants and personnel (performance bias)	Low risk	Stockings were handed out to the study participants by a person who was not involved in the examination and evaluation. The participant put on the stocking and interface pressure was measured independently by a person not involved in the other measuring routine. The stockings also looked similar.
Blinding of outcome assessment (detection bias)	Low risk	Interface pressure was measured independently by a person not involved in the other measuring routine.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Full details of participants enrolled and completed trial plus dropouts (although no power calculation noted). 2 participants excluded due to non‐compliance – remainder completed trial.
Selective reporting (reporting bias)	Low risk	All outcomes as reported in the methods section of study paper reported on.
Other bias	Low risk	No evidence of other bias.

ABI: ankle‐brachial index; AI: arterial inflow; AVVQ: Aberdeen Varicose Veins Questionnaire; BMI: body mass index; CEAP: Clinical, Etiology, Anatomy, Pathophysiology classification^a; CPGS: Chronic Pain Grade Scale; CVI: chronic venous insufficiency; DVT: deep vein thrombosis; EV: expelled volume; EVR/EVrel: expelled volume related to the foot volume; GECS: graduated elastic compression stocking; MFQ: Muscle Fatigue Questionnaire; MCS: medical compression stocking; MVO: maximum venous outflow; NYHA: New York Heart Association; PAD: peripheral arterial disease; PS: placebo stocking; Q: maximum rate of refilling of the foot volume; SD: standard deviation; SVT: superficial vein thrombosis; T_1/2: time taken for refilling of half the expelled volume; VAS: visual analogue scale; VCSS: Venous Clinical Severity Score.
^aCEAP: Clinical, Etiology, Anatomy, Pathophysiology classification: classification system for chronic venous disorders: includes a description of the clinical class (C) based upon objective signs, the aetiology (E), the anatomical (A) distribution of reflux and obstruction in the superficial, deep and perforating veins, and the underlying pathophysiology (P).

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Abramowitz 1973	Trial examined sclerotherapy vs compression. Trial had no control group to compare the compression group with.
Adamzcyk 2013	Data not stratified by CEAP.
Al Shammeri 2014	Data not stratified by CEAP.
Arnoldi 1976	Wrong patient population, combination of healthy volunteers and people with venous disease, results not stratified.
Austrell 1995	Participants did not meet inclusion criteria as they are not diagnosed with varicose veins.
Benigni 2003	Included people with chronic venous disease CEAP classification C1–C3. No subgroup analysis for those participants with CEAP C2 and above, which could be included in this review. Liaised with author who has no further results for this subgroup of patients only, therefore unable to include.
Benigni 2013	Study designed to evaluate donning and taking off compression stockings.
Biswas 2007	Participants underwent vascular surgery followed by randomisation to compression stockings.
Blazek 2013	Wrong patient population, study on hairdressers not selected by varicose vein symptoms.
Bond 1997	Participants underwent surgical intervention followed by randomisation to compression.
Bond 1999	Participants underwent surgery followed by randomisation to compression.
Buhs 1999	Data not stratified by CEAP.
Chant 1979	Assessment of support bandages following injection therapy.
Couzan 2009	Wrong patient population: participants with mild CVI.
Derman 1989	Participants were healthy women, not diagnosed with varicose veins.
Diamand 2012	Wrong patient population: people with moderate‐to‐severe CVI.
Diehm 1996	Males and females with substantial lower leg oedema due to CVI. Study compared compression with horse‐chestnut extract and placebo capsules (not placebo compression).
DRKS00008829	Study compared a compression system (Coban Fit) vs short‐stretch bandage (Rosidal).
DRKS00012258	Planned outcomes not relevant for review such as skin hydration, transepidermal water loss of the skin by means of Tewameter and Corneometer and skin roughness measurement by FOITS (fast optical in vivo topometry of human skin) camera.
DRKS00014743	Unclear if participants had varicose veins.
Fentem 1976	Study assessed healthy women without varicose veins.
Gandhi 1984	Unable to distinguish participants with varicose veins (contact with author attempted). Garments used were anti‐embolism, general support garments and bandages.
Genzel 1991	Study assessed people with healthy veins.
Griffin 2007	Trial compared pneumatic compression systems.
Gronbaek 1991	Study assessed people with superficial venous insufficiency.
Guest 2003	Participants were diagnosed with venous ulceration.
Häfner 2000	Data not stratified by CEAP.
Häfner 2001	Data not stratified by CEAP.
Hamel‐Desnos 2008	Participants underwent sclerotherapy followed by compression stockings.
Hamel‐Desnos 2010	Participants underwent sclerotherapy followed by randomisation to compression or no compression.
Houtermans‐Auckel 2009	Participants underwent surgical intervention followed by randomisation to compression stockings.
Jeanneret 2014	Data not stratified by CEAP.
Labropoulos 1994	Aim of study to assess immediate and long‐term effect of stocking use (measurements taken at end of study period or 4 weeks after stopping use of stockings). All participants wore compression stockings.
Lattimer 2017	Data not stratified by CEAP, measuring damage using plasma markers comparing standing, compression and leg elevation.
Lord 2004	Did not stratify data by healthy participants and those with varicose veins, assessed internal diameter of veins.
Makin 1982	Participants underwent sclerotherapy followed by compression.
Mariani 2011	Participants underwent surgical intervention followed by randomisation to compression.
Melrose 1979	Participants underwent surgical intervention followed by randomisation to compression.
Moehrle 2007	Participants were healthy runners and cyclists.
Mosti 2009	Participants underwent surgery followed by randomisation to compression.
Mosti 2010	Data not stratified by CEAP.
Mosti 2011	Included participants with chronic venous disease CEAP classification C2–C5. No subgroup analysis reported for those participants with CEAP C2–C4, which could be included in this review. Attempted to contact study author but received no reply.
Mosti 2012	Study used inelastic bandages, not compression hosiery.
Muller‐Buhl 1998	Data not stratified by CEAP.
NCT01793194	Wrong patient population as randomised pregnant women without varicose veins at recruitment
O'Hare 2010	Participants underwent sclerotherapy followed by randomisation for compression.
Park 2013	Brief report of preliminary study investigating a 'novel leg supporter.'
Perhoniemi 1983	Participants underwent varicose vein surgery then allocated to compression stockings or bandages.
Pohlmann 1997	Study used anti‐embolism stockings.
Rabe 2010	Participants were diagnosed with phlebitis, not varicose veins.
Raj 1981	Compression following injection sclerotherapy.
Raraty 1999	Participants underwent surgery followed by bandages or stockings.
Saliba 2020	Study randomised pregnant women, not randomised by varicose veins.
Schul 2009	Participants had isolated reticular veins and telangiectasia.
Thaler 2001	Participants did not meet inclusion criteria for this study as varicose veins were not present at the start of the trial.
Vayssairat 2000	Data not stratified by CEAP.
Weiss 1999a	Participants consisted of flight attendants on international flights.
Weiss 1999b	Participants underwent sclerotherapy followed by compression therapy.
Westphal 2019	Compared 2 stockings with same pressure and length, only difference being 1 stocking with integrated care.
Wolff 2011	Data not stratified by CEAP.
Zajkowski 2002	Participants of CEAP 4 and 5, 10/11 participants had prior surgery for venous disease.

CEAP: classification system for chronic venous disorders: includes a description of the clinical class (C) based upon objective signs, the aetiology (E), the anatomical (A) distribution of reflux and obstruction in the superficial, deep and perforating veins, and the underlying pathophysiology (P); CVI: chronic venous insufficiency.

Characteristics of ongoing studies [ordered by study ID]

DRKS00012259.

Study name	Efficacy of medical compression stockings with different interface pressures in patients with chronic venous insufficiency (CVI) of different severity
Methods	Study type: randomised controlled trial Allocation: randomised Intervention model: cross‐over Blinding: none (open label)
Participants	Age: 18–80 years Sex: both Inclusion criteria: CVI CEAP C1–C5; willingness and ability of the participant to wear compression stockings as well as follow the doctor's instructions and to comply with the planned visits; presence of written consent to participate in the study after a thorough investigation into the nature, significance, risks and scope of the clinical trial, as well as expected and undesirable effects of the trials; sufficient German language skills both written and spoken Exclusion criteria: chronic venous ulcer (CEAP C6); acute DVT; PAD; diabetes mellitus with neuropathy or peripheral arterial disorder; absence of CVI; non‐existent mobility; non‐signed declaration of consent; participation in another study
Interventions	Compression therapy with medical compression stockings with different interface pressure (Ccl 1, Ccl 2 and Ccl 3) in randomised order for 7 days each, no wash‐out phase between the wearing periods Arm 1: Ccl 1 (interface pressure 18–21 mmHg) Arm 2: Ccl 2 (interface pressure 23–32 mmHg) Arm 3: Ccl 3 (interface pressure 34–46 mmHg)
Outcomes	Primary outcome Volume of the lower limb (reduction of venous oedema due to the applied compression therapy); measured at the end of the 7‐day wearing phase using BT600 (company Bauerfeind) Secondary outcomes: Clinical findings (influence of the application of different Ccls on the clinical symptoms of the CVI) assessed at the end of a 7‐day wearing phase VEF (influence of the application of different Ccls on venous haemodynamic parameters in people with CVI), measured by strain gauge plethysmography at the end of the 7‐day wearing phase Interface pressure of the compression stockings measured with PicoPress after 7‐day wearing phase Subjective assessment of participants during the wearing phases, measured daily by means of questionnaires on the QoL
Starting date	26 April 2017
Contact information	Prof Dr Med Michael Jünger, Clinic and Polyclinic for Skin Diseases of the University Medicine Greifswald, Greifswald, Germany
Notes	DRKS website stated recruitment and follow‐up is complete.

NCT00766974.

Study name	Compression aided management of edema in patients with C3 venous disease
Methods	Study type: interventional (clinical trial) Estimated enrolment: 40 participants Allocation: randomised Intervention model: parallel assignment Blinding: none (open label)
Participants	Age: 18–80 years Sex: both Inclusion criteria: people with varicose veins exhibiting lower leg oedema; unilateral or bilateral oedema Exclusion criteria: generalised leg oedema from renal disease, heart failure, liver disease or other undetermined cause; acute infection; hepatitis; steroid use; immunodeficiencies including HIV; acute DVT; have had leg surgery or other orthopaedic procedure in past 6 months
Interventions	Intervention 1: anti‐embolism knee high stocking (13–18 mmHg) Intervention 2: knee‐high graded compression stocking (20–30 mmHg) Participants should wear stockings for 4 weeks
Outcomes	Primary outcome Oedema reduction measured by bioimpedance at 4 weeks Secondary outcome Clinical Venous Severity Score Improvement in QoL at 4 weeks
Starting date	October 2008
Contact information	Principal Investigator: Joseph Raffetto, MD, Boston VA Healthcare, West Roxbury, Massachusetts, US
Notes

NCT01402921.

Study name	Efficacy on volume reduction and tolerance of progressiv' Medical Compressive Therapy (MCT) V0322 BC in patients with chronic venous oedema
Methods	Study type: interventional (clinical trial) Actual enrolment: 92 participants Allocation: randomised Intervention model: parallel assignment Blinding: quadruple (participant, care provider, investigator, outcomes assessor)
Participants	Age: ≥ 18 years Sex: both Inclusion criteria: permanent chronic oedema of venous origin (C3 based on CEAP classification) confirmed by Doppler or Duplex ultrasound examination with reflux or obstruction (or both) on superficial, deep or perforator veins; pitting oedema; have given and signed written informed consent; registered with or benefiting from health insurance (mandatory for France) Exclusion criteria: use of compression therapy in the last 5 days before inclusion; common contraindications for MCT (arteriopathy, decompensated heart failure, infectious dermatitis; isolated lipoedema; isolated lymphoedema (Kaposi‐Stemmer sign); severe systemic disease (heart failure, renal failure, hepatic failure, untreated thyroid dysfunction, malnutrition with hypoproteinaemia); known hypersensitivity to any component of MCT; important limitation of ankle movement requiring a specific therapy; following treatment initiated or dose‐modified 1 month prior to inclusion: NSAID, corticosteroids, calcium blockers, ACE inhibitors, angiotensin II inhibitors, vasoconstrictors or vasodilators; hormonal treatment initiated or dose‐modified 1 month prior to inclusion; diuretic or phlebotonic treatment (or both) initiated or dose‐modified 1 month prior to inclusion; pregnancy, breastfeeding, planning to become pregnant or not using any form of contraception; linguistically or psychologically unable to understand the information given or who refuses to give his/her consent in writing; participation in another clinical trial; deprived of liberty for administrative, medical and legal reasons; may not be compliant with the constraints imposed by the protocol
Interventions	Experimental: Elastic Medical Compressive Therapy device: V0322 BC Placebo comparator: placebo device V0322BC verum medical compressive therapy is a progressive compressive sock with: ankle pressure 10 mmHg and calf pressure 23 mmHg Placebo device is a progressive compressive sock with: ankle pressure < 5 mmHg and calf pressure < 7 mmHg Duration: 3 months of daily treatment
Outcomes	Primary outcome Target leg volume reduction of chronic venous oedema measured by volumetry method with water displacement at 3 months (day 90) Secondary outcomes Functional symptoms by VAS (pain, heaviness) at each visit by the participant (day 0, day 7, day 30 and day 90) QoL. SQOR‐V and ABC‐V (FARDEAU) score (day 0, day 7, day 30 and day 90) Bodyweight variation (day 0, day 7, day 30 and day 90) Suprafacial thickness, duplex measurement (day 0, day 7, day 30 and day 90) Assessment of local tolerance (examination of the skin) and safety (general clinical examination and reported adverse events) (day 7, day 30 and day 90)
Starting date	January 2011
Contact information	Location: Centre Hospitalo‐Universitaire Grenoble, Grenoble, Isère, France, 38000 Sponsors and Collaborators: Pierre Fabre Medicament
Notes	ClinicalTrials.gov record reports study was completed March 2012.

NCT03429959.

Study name	SOCKNLEG compression stocking kit: user friendliness (SOCKNLEGZH)
Methods	Study type: interventional (clinical trial) Estimated enrolment: 47 participants Allocation: randomised Intervention model: cross‐over assignment Blinding: none (open label)
Participants	Age: ≥ 65 years Sex: all Inclusion criteria: informed consent as documented by signature; male or postmenopausal female; diagnosed venous insufficiency stage C3–C6 (according to CEAP classification for venous diseases) Exclusion criteria: venous leg ulcer with a surface > 5 cm²; PAD or media calcinosis (ABI < 0.8 or > 1.3); difference in brachial blood pressure > 20 mmHg in both arms; suspected polyneuropathy with ≥ 4 sensible test areas, measured using the Semmes‐Weinstein‐Monofilament‐Test; inability to reach the forefoot with their hands; inability to follow the procedures of the study; bed‐ridden hospitalised patients who are unable to leave the bed or sit upright for a few consecutive hours
Interventions	Experimental: SOCKNLEG device Active comparator: Sigvaris cotton device All participants will try on both study stockings in the order of their allocated group, and will rate their donning and doffing success with a questionnaire. The participants will then wear only the assigned study stocking of their allocated group for 1 day, and rate its comfort again at the end of the day. The donning and doffing success will also be rated by the study investigator. Leg volume measurements of the study leg will be taken at each visit to determine oedema prevention
Outcomes	Primary outcome Number of participants who completely don the 2 investigated leg compression devices (through study completion, within 7 months) Secondary outcomes Number of participants who completely doff the 2 investigated leg compression devices (through study completion, within 7 months) Patient evaluation of user friendliness at 3 days Evaluation of user friendliness using the ICC compression questionnaire Measuring oedema prevention of the compression stockings by comparison of leg volume measurement at V4 to V3 and V4 to V2 at 3 days Assessment by measuring leg volume at the morning visit 3, compared to leg volume at the evening visit 4 and by comparing the leg volumes of visit 4 (compression) to visit 2 (no compression for 1 day) Time needed to don and doff the 2 investigated leg compression at 3 days Time in minutes and seconds needed to don and doff each study stocking, measured by study investigator
Starting date	10 January 2018
Contact information	Prof Juerg Hafner MD Caroline S Buset MD Department of Dermatology, University Hospital of Zurich, Switzerland
Notes

NCT03743597.

Study name	SOCKNLEG compression stocking kit: physical properties (SOCKNLEGLCA)
Methods	Study type: interventional (clinical trial) Estimated enrolment: 35 participants Allocation: randomised Intervention model: cross‐over assignment Blinding: none (open label)
Participants	Age: ≥ 65 years Sex: both Inclusion criteria: informed consent as documented by signature; men or postmenopausal women; diagnosed venous insufficiency stage C3–C6 (according to CEAP classification); indication of a compression therapy by medical compression stocking Exclusion criteria: PAD or media calcinosis (ABI < 0.8 or > 1.3); suspected polyneuropathy with ≤ 4 sensible test areas, measured using the Semmes‐Weinstein‐Monofilament‐Test; advanced heart insufficiency (NYHA III–IV); contraindications to compression therapy; known allergies to any components of the stocking material; inability to follow the procedures of the study
Interventions	Experimental: SOCKNLEG device (innovative multi‐layer leg compression stocking, compression strength CEN Ccl II (European compression strength) with compression at the ankle of 23–32 mmHg, product composition understocking (polyamide, cotton, spandex), overstocking (polyamide, spandex)) Active comparator: Sigvaris cotton device (standard single leg compression stocking, compression strength CEN Ccl II (European compression strength) with compression at the ankle of 23–32 mmHg, product composition 1 stocking (polyamide, spandex, cotton)) All examinations will be conducted in all participants and with both stockings 1 after the other
Outcomes	Primary outcome SSI values of both stockings in mmHg measured at point cB1 on the leg at 1 day, during study visit The SSI is a substraction of the interface pressures measured with a pressure probe on the leg of the study participant in standing and supine position while wearing a compression stocking. The point cB1 is a thereby a standard measuring point at the distal insertion of the gastrocnemius muscle of the leg. Secondary outcomes SSI values of both stockings in mmHg measured at point cC on the leg at 1 day, during study visit Comparing the SSI at point cC of both stockings with each other and with the standard SSI values at point cB1. The point cC is a new measuring point at the largest circumference of the calf. DSI values of both stockings in mmHg at 1 day, during study visit The DSI is a substraction of the interface pressures measured at each point (cC and cB1) on the leg during wiping of the foot while wearing a compression stocking. Measuring instruments are again the pressure probes. VEF of both stockings in % at 1 day, during study visit Non‐invasive measurement of the venous filling volumes of the leg with a strain gauge plethysmography the Angioflow2 (Microlabitalia, Padua, Italy). Interface pressures at point cB on the leg in mmHg at 1 day, during study visit The point cB is the point of the smallest circumference of the leg and is the standard measuring point for compression strength of a leg compression stocking. Measured with a pressure probe on the leg of the study participant under the compression stocking.
Starting date	19 November 2018
Contact information	Prof Juerg Hafner MD Caroline S Buset MD Department of Dermatology, University Hospital of Zurich, Switzerland
Notes

RBR‐5n9cmf.

Study name	Evaluation of the effect of compression stocking containing natural product in the treatment of ulcers and varicose veins
Methods	Study type: randomised controlled trial with 3 arms Estimated enrolment: 30 participants Allocation: randomised Intervention model: parallel Masking: triple blind
Participants	Age: 30–59 years Sex: both Inclusion criteria: volunteers with varicose veins, varicose veins plus oedema, hyperpigmentation, lipodermatosclerosis, healed venous ulcer or active ulcer; similar impairment of the saphenous vein Exclusion criteria: volunteers with telangiectasias; cognitive alterations; diabetes; neuropathy; with erysipelas; lymphangitis; DVT; ulcer of non‐venous origin; psychiatric disorders; dementia; not speaking or understanding the Portuguese language; use of antibiotic or venoactive drugs in the last 6 months prior to the start of the research; sclerotherapy of lower limbs; surgical procedure; use of Unna boot, multi‐layer dressing or dressing with topical medicine; morbidly obese; pregnant women; women at risk of pregnancy
Interventions	Experimental group: 10 participants will use compression stockings containing nanoencapsulated hesperetin and placebo for oral use (every 12 hours) Control group: 10 participants will use conventional compression stocking and venoactive drug (hesperidin 450 mg + diosmin 50 mg) for oral use (every 12 hours) Placebo group: 10 participants will use conventional compression stocking and placebo for oral use (every 12 hours) All participants should wear the received stockings immediately after waking up and remain with them for 6 hours All participants will be treated for 6 months
Outcomes	Primary outcomes Healing of ulcers in the 6‐month period comprised in the study, verified by reduction of the size of the wound using the software Image J. The lesions with reduction > 70% of their total extension will be considered healed. Improvement in participants' QoL after 6 months of treatment. This outcome will be measured by the volunteers' responses to the Aberdeen Varicose Veins Questionnaire and the Wilcoxon test will be performed to check whether the participants achieved (P < 0.05) or did not improve satisfactorily Secondary outcomes Reduction of pain reported by the volunteer in the EVA questionnaire. This outcome will be measured according to the participants' responses using the Wilcoxon test to check whether the participants achieved (P < 0.05) or did not improve satisfactorily
Starting date	17 July 2018
Contact information	Paula dos Passos Menezes, Universidade Federal de Sergipe, São Cristóvão, Brazil
Notes

ABC‐V (FARDEAU): Assessment of Burden in Chronic disease – Venous questionnaire; ABI: ankle‐brachial index; ACE: angiotensin‐converting enzyme; Ccl: compression class; Clinical, Etiology, Anatomy, Pathophysiology classification^a; CVI: chronic venous insufficiency; DSI: Dynamic Stiffness Index; DVT: deep vein thrombosis; EVA: Echelle Visuelle Analogique (VAS for assessment of pain); ICC: International Compresssion Club; MCT: medical compression therapy; NSAID: non‐steroidal anti‐inflammatory drug; NYHA: New York Heart Association; PAD: peripheral arterial disease; QoL: quality of life; SSI: Static Stiffness Index; SQOR‐V: Specific Quality of Life and Outcome Response – Venous questionnaire; VAS: visual analogue scale; VEF: venous ejection fraction.
^aCEAP: Clinical, Etiology, Anatomy, Pathophysiology classification: classification system for chronic venous disorders: includes a description of the clinical class (C) based upon objective signs, the aetiology (E), the anatomical (A) distribution of reflux and obstruction in the superficial, deep and perforating veins, and the underlying pathophysiology (P).

Differences between protocol and review

2021 version

We added a secondary outcome 'Comfort, tolerance and acceptability of wearing stockings' as we deemed this was an important outcome relevant for patients.

To reflect the objective of this review more closely, we changed the title of this review from 'Compression stockings for the initial treatment of varicose veins in patients without venous ulceration' to 'Graduated compression stockings for the initial treatment of varicose veins in people without venous ulceration.'

2011 version

To reflect the objective of this review more closely, the title of this review was changed from 'Compression stockings for varicose veins' to 'Compression stockings for the initial treatment of varicose veins in patients without venous ulceration.'

Contributions of authors

SS selected trials, assessed risk of bias, extracted data and wrote the review.

LR contributed to the manuscript.

MS selected trials, assessed risk of bias, extracted data and wrote the review.

Sources of support

Internal sources

• No sources of support provided

External sources

• Chief Scientist Office, Scottish Government Health Directorates, The Scottish Government, UK

  The Cochrane Vascular editorial base is supported by the Chief Scientist Office.

Declarations of interest

SS: none.

LR: none.

MS: none known. MS declares that she is the Managing Editor of Cochrane Vascular. For the purpose of this review, all editorial tasks were carried out by other members of the editorial base.

New search for studies and content updated (no change to conclusions)