Therapeutics
After a first proximal DVT, compression stockings did not prevent the postthrombotic syndrome
Kahn SR, Shapiro S, Wells PS, et al; SOX trial investigators. Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial. Lancet. 2014;383:880-8.
Clinical impact ratings: F ★★★★★★✩ H ★★★★★★✩ Question In patients with a first proximal deep venous thrombosis (DVT), are elastic compression stockings (ECSs) better than placebo stockings for preventing the postthrombotic syndrome (PTS)?
Methods Design: Randomized placebo-controlled trial (SOX trial). ClinicalTrials.gov NCT00143598; Current Controlled Trials ISRCTN71334751.
to 0.8, SF-36 mental component score 0.3, CI −1.5 to 2.1) or disease-specific (VEINES-QOL 0.1, CI −1.0 to 1.2) quality of life at 12 months.
Conclusion In patients with a first proximal deep venous thrombosis, elastic compression stockings did not reduce the postthrombotic syndrome compared with placebo stockings. *See Glossary.
Allocation: Concealed.* Blinding: Blinded* (patients, clinicians, study staff, and statisticians).
Source of funding: Canadian Institutes of Health Research.
Follow-up period: 2 years.
For correspondence: Dr. S.R. Kahn, Jewish General Hospital, Montreal, QC, Canada. E-mail [email protected]. ■
Setting: 24 centers in Canada and the USA.
Commentary
Patients: 806 patients (mean age 55 y, 60% men) who had a first, symptomatic, ultrasound-confirmed DVT in the popliteal or more proximal deep leg veins in the previous 14 days. Exclusion criteria included life expectancy < 6 months, initial use of thrombolytic therapy for acute DVT, or contraindication to or inability to use compression stockings.
Moderate-to-severe PTS causes chronic pain and disability in as many as 20% of patients treated for lower-extremity DVT (1). Previous trials showed that ECSs, applied to achieve 30 to 40 mm Hg at the ankle, reduced risk for PTS by about 50% (2, 3), but the SOX study found no benefit. These discordant findings are probably explained by differences in study design: SOX is the only trial in which both patients and providers were blinded to treatment assignment. Although blinding may not be critical in some clinical trials, it is essential for study validity when the primary endpoint is subjective. Indeed, results of the methodologically rigorous SOX trial strongly suggest that assessments of treatment effect in the previous unblinded trials were biased by knowledge of treatment assignment. The absolute rates of PTS in SOX were lower than expected, perhaps because the anticoagulant therapy (an intervention thought to reduce PTS risk) in SOX was more aggressive than in previous reports; a placebo effect from the sham stockings may also have contributed to the low PTS rate in the control group.
Intervention: Graduated ECSs, 30 to 40 mm Hg (n = 410), or placebo stockings, < 5 mm Hg compression at the ankle (n = 396). Stockings were replaced ≤ every 6 months. Outcomes: PTS using Ginsberg criteria (ipsilateral leg pain and swelling lasting ≥ 1 mo that is worse with prolonged sitting or standing or at the end of the day and better with leg elevation and after sleep at night). Other outcomes included generic (SF-36 questionnaire) and disease-specific (VEINES-QOL/Sym questionnaire) quality of life, each with > 80% follow-up at ≤ 12 months. 800 patients were needed to detect a 33% relative risk reduction in PTS at 2 years from 30% in the placebo group (power 80%, α2-sided = 0.05), assuming 25% loss to follow-up, including deaths. Patient follow-up: 77% completed the study, and 8.9% died (modified intention-to-treat analysis).
Main results ECSs did not reduce PTS compared with placebo stockings (Table). Groups did not differ for generic (difference in change from baseline, SF-36 physical component score −1.2, 95% CI −3.2 Elastic compression stockings (ECSs) vs placebo stockings in patients with a first proximal DVT† Outcome
ECSs
Placebo
PTS (Ginsberg criteria‡)
14%
13%
At 750 d RRI (95% CI) NNT (CI) 12% (−26 to 67)
Not significant
†DVT = deep venous thrombosis; PTS = postthrombotic syndrome; other abbreviations defined in Glossary. RRI and CI calculated from hazard ratio and control event rate in article. ‡Ipsilateral leg pain and swelling lasting ≥ 1 mo that is worse with prolonged sitting or standing or at the end of the day and better with leg elevation or after sleep at night.
15 April 2014 | ACP Journal Club | Volume 160 • Number 8
For some patients who have persistent leg pain and swelling despite anticoagulation, ECSs may provide symptomatic relief. It is possible that future studies could define a population for whom ECSs are an effective primary prevention strategy for PTS. For now, however, the SOX trial shows that fitted ECSs do not reduce risk for PTS and need not be routinely recommended to patients with leg DVT. David Garcia, MD University of Washington Seattle, Washington, USA References 1. Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996;125:1-7. 2. Brandjes DP, Büller HR, Heijboer H, et al. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet. 1997;349:759-62. 3. Prandoni P, Lensing AW, Prins MH, et al. Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. Ann Intern Med. 2004;141:249-56.
© 2014 American College of Physicians
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/929992/ by a Weill Medical College User on 07/18/2017
JC7
After a first proximal DVT, compression stockings did not prevent the postthrombotic syndrome
Kahn SR, Shapiro S, Wells PS, et al; SOX trial investigators. Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial. Lancet. 2014;383:880-8.
Clinical impact ratings: F ★★★★★★✩ H ★★★★★★✩ Question In patients with a first proximal deep venous thrombosis (DVT), are elastic compression stockings (ECSs) better than placebo stockings for preventing the postthrombotic syndrome (PTS)?
Methods Design: Randomized placebo-controlled trial (SOX trial). ClinicalTrials.gov NCT00143598; Current Controlled Trials ISRCTN71334751.
to 0.8, SF-36 mental component score 0.3, CI −1.5 to 2.1) or disease-specific (VEINES-QOL 0.1, CI −1.0 to 1.2) quality of life at 12 months.
Conclusion In patients with a first proximal deep venous thrombosis, elastic compression stockings did not reduce the postthrombotic syndrome compared with placebo stockings. *See Glossary.
Allocation: Concealed.* Blinding: Blinded* (patients, clinicians, study staff, and statisticians).
Source of funding: Canadian Institutes of Health Research.
Follow-up period: 2 years.
For correspondence: Dr. S.R. Kahn, Jewish General Hospital, Montreal, QC, Canada. E-mail [email protected]. ■
Setting: 24 centers in Canada and the USA.
Commentary
Patients: 806 patients (mean age 55 y, 60% men) who had a first, symptomatic, ultrasound-confirmed DVT in the popliteal or more proximal deep leg veins in the previous 14 days. Exclusion criteria included life expectancy < 6 months, initial use of thrombolytic therapy for acute DVT, or contraindication to or inability to use compression stockings.
Moderate-to-severe PTS causes chronic pain and disability in as many as 20% of patients treated for lower-extremity DVT (1). Previous trials showed that ECSs, applied to achieve 30 to 40 mm Hg at the ankle, reduced risk for PTS by about 50% (2, 3), but the SOX study found no benefit. These discordant findings are probably explained by differences in study design: SOX is the only trial in which both patients and providers were blinded to treatment assignment. Although blinding may not be critical in some clinical trials, it is essential for study validity when the primary endpoint is subjective. Indeed, results of the methodologically rigorous SOX trial strongly suggest that assessments of treatment effect in the previous unblinded trials were biased by knowledge of treatment assignment. The absolute rates of PTS in SOX were lower than expected, perhaps because the anticoagulant therapy (an intervention thought to reduce PTS risk) in SOX was more aggressive than in previous reports; a placebo effect from the sham stockings may also have contributed to the low PTS rate in the control group.
Intervention: Graduated ECSs, 30 to 40 mm Hg (n = 410), or placebo stockings, < 5 mm Hg compression at the ankle (n = 396). Stockings were replaced ≤ every 6 months. Outcomes: PTS using Ginsberg criteria (ipsilateral leg pain and swelling lasting ≥ 1 mo that is worse with prolonged sitting or standing or at the end of the day and better with leg elevation and after sleep at night). Other outcomes included generic (SF-36 questionnaire) and disease-specific (VEINES-QOL/Sym questionnaire) quality of life, each with > 80% follow-up at ≤ 12 months. 800 patients were needed to detect a 33% relative risk reduction in PTS at 2 years from 30% in the placebo group (power 80%, α2-sided = 0.05), assuming 25% loss to follow-up, including deaths. Patient follow-up: 77% completed the study, and 8.9% died (modified intention-to-treat analysis).
Main results ECSs did not reduce PTS compared with placebo stockings (Table). Groups did not differ for generic (difference in change from baseline, SF-36 physical component score −1.2, 95% CI −3.2 Elastic compression stockings (ECSs) vs placebo stockings in patients with a first proximal DVT† Outcome
ECSs
Placebo
PTS (Ginsberg criteria‡)
14%
13%
At 750 d RRI (95% CI) NNT (CI) 12% (−26 to 67)
Not significant
†DVT = deep venous thrombosis; PTS = postthrombotic syndrome; other abbreviations defined in Glossary. RRI and CI calculated from hazard ratio and control event rate in article. ‡Ipsilateral leg pain and swelling lasting ≥ 1 mo that is worse with prolonged sitting or standing or at the end of the day and better with leg elevation or after sleep at night.
15 April 2014 | ACP Journal Club | Volume 160 • Number 8
For some patients who have persistent leg pain and swelling despite anticoagulation, ECSs may provide symptomatic relief. It is possible that future studies could define a population for whom ECSs are an effective primary prevention strategy for PTS. For now, however, the SOX trial shows that fitted ECSs do not reduce risk for PTS and need not be routinely recommended to patients with leg DVT. David Garcia, MD University of Washington Seattle, Washington, USA References 1. Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996;125:1-7. 2. Brandjes DP, Büller HR, Heijboer H, et al. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet. 1997;349:759-62. 3. Prandoni P, Lensing AW, Prins MH, et al. Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. Ann Intern Med. 2004;141:249-56.
© 2014 American College of Physicians
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/929992/ by a Weill Medical College User on 07/18/2017
JC7
