Elsevier

The Lancet

Volume 383, Issue 9920, 8–14 March 2014, Pages 880-888
The Lancet

Articles
Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial

https://doi.org/10.1016/S0140-6736(13)61902-9Get rights and content

Summary

Background

Post-thrombotic syndrome (PTS) is a common and burdensome complication of deep venous thrombosis (DVT). Previous trials suggesting benefit of elastic compression stockings (ECS) to prevent PTS were small, single-centre studies without placebo control. We aimed to assess the efficacy of ECS, compared with placebo stockings, for the prevention of PTS.

Methods

We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA. Patients were randomly assigned to study groups with a web-based randomisation system. Patients presenting with a first symptomatic, proximal DVT were potentially eligible to participate. They were excluded if the use of compression stockings was contraindicated, they had an expected lifespan of less than 6 months, geographical inaccessibility precluded return for follow-up visits, they were unable to apply stockings, or they received thrombolytic therapy for the initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months or later using Ginsberg's criteria (leg pain and swelling of ≥1 month duration). We used a modified intention to treat Cox regression analysis, supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment. This study is registered with ClinicalTrials.gov, number NCT00143598, and Current Controlled Trials, number ISRCTN71334751.

Findings

From 2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396 placebo ECS. The cumulative incidence of PTS was 14·2% in active ECS versus 12·7% in placebo ECS (hazard ratio adjusted for centre 1·13, 95% CI 0·73–1·76; p=0·58). Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings.

Interpretation

ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT.

Funding

Canadian Institutes of Health Research.

Introduction

Post-thrombotic syndrome (PTS) is a chronic disorder that develops in 25–50% of patients after deep venous thrombosis (DVT).1, 2 Its clinical features range from minor limb swelling and discomfort to severe leg pain, intractable oedema, irreversible skin changes, and leg ulceration. PTS reduces quality of life3, 4 and imposes a substantial economic burden on patients and society.5, 6

Prevention of PTS is important since treatments are not very effective.7, 8 Ideally, PTS is averted entirely by primary prevention of the initial DVT with the judicious use of thromboprophylaxis. However, thromboprophylaxis remains underused and the occurrence of at least half of all cases of DVT are unpredictable, hence are not preventable. Therefore, prevention of PTS after DVT is an important goal.

Elastic compression stockings (ECS) have the potential to prevent PTS by reducing venous hypertension and reflux, which are thought principal factors in the pathophysiology of PTS.9 The findings of two previous randomised trials10, 11 suggested that wearing ECS for 2 years after proximal DVT halved the risk of developing PTS. However, both trials were small, done in a single centre, and were not placebo-controlled. Stockings are cumbersome to apply, and can be hot, constricting, and itchy. They can cost $100 or more per pair, need to be replaced twice a year due to wear and tear, and might not be covered by public health care plans. Furthermore, a survey of thrombosis physicians showed a lack of agreement on the benefits of ECS or the optimum timing, indication, and duration of their use.12 In view of the above, we believed that a large, placebo-controlled trial was needed to provide definitive evidence of efficacy, or lack of efficacy, of ECS. This would allow physicians to make informed, evidence-based decisions on the use of compression stockings in patients with DVT. We therefore did the SOX trial, a multicentre, randomised, placebo-controlled trial to establish whether ECS prevent PTS after proximal DVT. We also assessed the effect of ECS on severity of PTS, recurrent venous thromboembolism, venous valvular reflux, and quality of life.

Section snippets

Participants

Between June, 2004, and February, 2010, we enrolled patients in 24 centres in Canada and the USA. The study originally had a two by two factorial design that tested a second intervention, celecoxib versus placebo taken twice-daily for 30 days. Because of concerns about the safety of COX-2 inhibitors13 it was decided to abandon this intervention after 26 patients were enrolled and redesign the study as a parallel group trial of active versus placebo ECS.14

Patients presenting with a first

Results

Figure 1 shows the trial profile. Three patients were identified as ineligible soon after randomisation and were excluded from further analysis (ie, modified intention-to-treat). Baseline characteristics were similar between the two groups (table 1). Overall, 483 (60·1%) of 803 patients were men, mean age was 55·1 years (SD 15·5), and 699 (87·1%) of 803 were outpatients. Mean time from DVT diagnosis to randomisation was 4·7 days (SD 3·9). The most proximal extent of DVT was iliac vein in 93

Discussion

Our findings show that wearing a graduated ECS did not reduce the incidence of PTS at 2 years in patients with a first proximal DVT, compared with wearing placebo stockings. Similarly, ECS did not affect the occurrence of venous ulcers, rate of recurrent venous thromboembolism, prevalence of venous valvular reflux at 12 months, or generic or venous disease specific quality of life. These findings were consistent across subgroups defined by age, BMI, and extent of DVT. We believe a true subgroup

References (34)

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