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Appelen D, van Loo E, Prins MH, Neumann MH, Kolbach DN. Compression therapy for prevention of post‐thrombotic syndrome. Cochrane Database Syst Rev. 2017; 9(9): CD004174.

Azirar S, Appelen D, Prins MH, Neumann MH, de Feiter AN, Kolbach DN. Compression therapy for treating post‐thrombotic syndrome. Cochrane Database Syst Rev. 2019; 9(9): CD004177.

Study Population: Prevention: five trials comprising 1,393 patients with deep vein thrombosis. Treatment: four trials comprising 116 patients with post‐thrombotic symptoms

Efficacy Endpoints

Prevention of postthrombotic syndrome (prevention endpoint); reduction in severity of postthrombotic symptoms (treatment endpoint)

Harm Endpoints

Discomfort, pain, and pressure sores (prevention harm endpoint); discomfort, skin damage, pain, arterial leg ulceration, recurrence of thrombosis (treatment harm endpoint)

Narrative

Postthrombotic syndrome (PTS) arises from venous outflow restriction.1^, 2 It may occur in 20% to 50% of patients after a deep vein thrombosis (DVT) and is characterized by edema, skin changes, pruritus, paresthesias, and pain, which can adversely affect quality of life (QOL).1^, 2 Adequate dosing and duration of anticoagulation for DVTs may lower the likelihood of PTS3; however, compression therapy has also been used for prevention and treatment.4^, 5^, 6 While this therapy, which includes bandaging or compression stockings, has been proposed to reduce edema and improve QOL,6^, 7 clinicians, articles, and guidelines differ in their recommendations concerning the use of these devices for prevention and treatment of PTS.1^, 2^, 3^, 4^, 5^, 6 This article discusses two Cochrane reviews evaluating prevention and treatment of PTS.5^, 8

Prevention: The systematic review evaluating prevention of PTS included randomized controlled trials (RCTs) investigating compression therapy in patients with DVT, diagnosed by ultrasonography or venography.5 The primary outcome was the incidence of PTS up to 2 years after diagnosis, which was defined by the individual study authors. Secondary outcomes included venous thromboembolism, adverse effects (discomfort, pain, and pressures sores), patient satisfaction and QOL, and compliance.

The authors initially included 10 RCTs (n = 2,361 patients) with mean follow‐up ranging from 2 to 6.3 years. However, due to differences in intervention types and inadequate data, they were only able to pool five trials (n = 1,393 patients) for meta‐analysis. All trials compared elastic compression stockings (pressure 20–40 or 30–40 mm Hg at the ankle) versus no intervention. The stockings were not statistically associated with reduction in incidence of PTS (relative risk [RR] = 0.62, 95% confidence interval [CI] = 0.38 to 1.01), reduction in incidence of severe PTS (RR = 0.78, 95% CI = 0.53 to 1.15), or difference in DVT recurrence (RR = 0.94, 95% CI = 0.69 to 1.28). There was no difference between knee‐high and thigh‐high stockings (RR = 0.92, 95% CI = 0.66 to 1.28). Three studies reported patient satisfaction and QOL, with one of these trials finding more rapid and pronounced improvement in QOL with compression compared to bed rest. No trials described serious adverse events.

Treatment: The systematic review evaluating compression dressings for reducing the severity of PTS in patients with objectively diagnosed DVT included four trials (n = 116 patients).8 The primary outcome was severity of PTS as defined in each study (based on a systematic clinical history and scoring of examinations) and adverse effects including recurrence of thrombosis, discomfort, skin damage, pain, and arterial leg ulceration.

Because of the presence of methodologic and endpoint heterogeneity among the studies, the authors of the systematic review elected not to pool data to perform a meta‐analysis. Among the four trials reviewed, two evaluated gradual elastic compression stockings,9^, 10 and two evaluated intermittent compression devices.11^, 12

Individual Trials:
Gradual elastic compression
One trial compared gradual elastic compression stockings (40 mm Hg pressure at the ankles) to placebo stockings in patients with PTS 1 year after DVT diagnosis.9 The endpoint was treatment failure, defined as pain and swelling that did not improve, or worsened, after the first 3 months; worsening of symptoms during further follow‐up; symptoms preventing participants from performing their daily activities for 5 or more days in any 3‐month period; or developing a leg ulcer. This study did not show any significant difference in treatment failure between groups, and it did not assess satisfaction or QOL. Since the prevalence of PTS was very low the investigators concluded PTS is rare and compression dressings were not necessary.9 Another trial evaluated the hemodynamic performance of medical elastic compression devices based on a symptom scale and air plethysmography, with each patient acting as his/her own control.10 The measured endpoints were venous filling index, venous filling time, and venous volume. In this study, all types of compression dressings significantly improved the hemodynamic endpoints compared with no compression.10 This study found that 21 patients changed their preference of leg stocking, with eight of these 21 patients preferring above‐the‐knee stockings.10 Neither trial reported adverse events.9^, 10

Intermittent compression
One trial evaluated the Jobst extremity pump (15 mm Hg in the control group vs. 50 mm Hg pressure in the active treatment group) in 15 patients, with treatment considered successful if patients had improved symptom score and preferred the therapeutic pressure.11 The second trial evaluated the Venowave device, a lower‐limb venous return device.12 They performed a placebo‐controlled, double‐blind, crossover RCT, with a primary outcome of at least moderate improvement in symptoms, and willingness to continue the device. The first trial found 80% of patients (11/15) preferred higher pressure compression,11 with symptom scores at therapeutic levels of 14.3 (standard deviation [SD] ±5.4) compared to 16.5 (SD±6.1) for placebo levels. The second study found improved scores and QOL based on VEINES‐QOL score (mean difference = 2.9 points) in patients utilizing the Venowave device.12 This latter trial also found 9% of patients experienced an adverse event such as leg swelling, irritation, superficial skin bleeding, or pruritus.12

Caveats

Both of these systematic reviews contain limitations.5^, 8 In the Cochrane review evaluating prevention of PTS, included studies demonstrated no significant effect although considerable heterogeneity was present due to variation in follow‐up, time following DVT, blinding, size of compression stockings, pressure and length of stockings, and scoring systems utilized for PTS assessment. It is notable that pooled results found endpoints suggesting the potential for clinically important effects, although the trials may have been underpowered to detect them.

The Cochrane review evaluating treatment of PTS found very‐low‐certainty evidence concerning graduated elastic compression stockings, with one study reporting beneficial hemodynamic effects and one finding no benefit on severity of PTS.10^, 11 Authors of the Cochrane review did not perform quantitative meta‐analysis due to significant heterogeneity, instead presenting the evidence narratively.8 We applaud this choice, which is why we elected to provide a summary of each trial above. The authors’ narrative description of each study and their findings seems far more likely to be helpful to patients and clinicians than any single numerical result hoping to represent such a wide variety of methods and interventions.8 Included studies utilized different methodologies and evaluated different devices, populations, symptom severity scales, and outcomes.9^, 10^, 11^, 12 Symptom scoring systems and classification systems varied in the included studies. This lack of standardization is a significant limitation in comparing and contrasting study results, and several studies did not assess patient‐centered outcomes such as QOL. Most also evaluated primary outcomes at less than 5 months. Because PTS is a chronic condition, evaluation of therapies for longer time periods may be needed to demonstrate sustained efficacy. Sample sizes were also small, with 116 subjects in total. One included trial used a non–patient‐centered endpoint.10

The two systematic reviews summarized here highlight the paucity of reliable data in supporting or refuting the effectiveness of compression therapy for preventing or reducing the symptoms of PTS.5^, 8 Based on the presented data, authors rate the certainty of evidence for prevention as low, and the evidence for treatment of PTS symptoms as very low or low. We agree and have thus assigned a color of yellow (unclear if benefits) for the use of elastic compression stockings for prevention and treatment of PTS symptoms. Further studies are needed using validated and uniform symptom scales, which also evaluate long‐term benefits and adverse events.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.

Author

Brit Long, MD; Michael Gottlieb, MD
Supervising Editors: Shahriar Zehtabchi, MD

Published/Updated

February 3, 2021