Correspondence
I declare no competing interests.
David Shaw [email protected] Institute for Biomedical Ethics, University of Basel, CH-4056 Basel, Switzerland 1
Shaw D. The right to participate in high-risk research. Lancet 2014; 383: 1009–11.
Compression stockings to prevent postthrombotic syndrome
post-thrombotic syndrome: heparin, a drug discovered a century ago by Jay McLean (in 1916), which revolutionised deep-vein thrombosis prognosis.4 Moreover, a well-conducted anticoagulation treatment has also been associated with a decreased rate of post-thrombotic syndrome. Therefore, the results of the SOX trial should not be “leaving doctors empty handed”,2 but should rather reinforce their role in offering a high-quality anticoagulant treatment to their patients. An ongoing international placebocontrolled trial should assess more precisely the effect of heparin on the natural history of post-thrombotic syndrome after a distal deep-vein thrombosis (NCT00539058). The effect of new oral anticoagulants on the prevention of post-thrombotic syndrome is another important issue.5 We declare no competing interests.
In their SOX trial (March 8, p 880),1 Susan Kahn and colleagues did not report any benefit of elastic compression stockings in preventing post-thrombotic syndrome. According to Arina ten Cate-Hoek,2 this unexpected result “could have an important effect on daily practice, leaving doctors empty handed”.2 In 1946, in The Lancet, Swedish surgeon Gunnar Bauer reported on the effectiveness of heparin on long-term sequelae of deep-vein thrombosis.3 In the absence of anticoagulants, 5 years after an objectively confirmed “late” (ie, proximal) deep-vein thrombosis, all patients developed venous insufficiency and 20% a venous leg ulcer. Heparin reduced by 78·9% the risk of developing signs of post-thrombotic syndrome after deep-vein thrombosis.3 Interestingly, Bauer’s reported prevalence of post-thrombotic syndrome at 3 years in patients treated with heparin (up to 26·3%) did not differ substantially from the prevalence of post-thrombotic syndrome reported in contemporary cohorts. We therefore believe that doctors already have a very, although not fully, effective treatment to prevent www.thelancet.com Vol 384 July 12, 2014
*Jean-Philippe Galanaud, Marc Righini, Isabelle Quéré [email protected] Department of Internal Medicine and Clinical Investigation Centre, University Hospital Saint Eloi, Montpellier 34295, France (J-P G, IQ); and Vascular Medicine Unit, Geneva University Hospital, Geneva, Switzerland (MR) 1
2
3
4
5
Kahn SR, Shapiro S, Wells PS, et al. Compression stockings to prevent postthrombotic syndrome: a randomised placebocontrolled trial. Lancet 2014; 383: 880–88. Ten Cate-Hoek AJ. Elastic compression stockings—is there any benefit? Lancet 2014; 383: 851–53. Bauer G. Thrombosis; early diagnosis and abortive treatment with heparin. Lancet 1946; 247: 447–54. Galanaud JP, Laroche JP, Righini M. The history and historical treatments of deep vein thrombosis. J Thromb Haemost 2013; 11: 402–11. Prandoni P. Healthcare burden associated with the post-thrombotic syndrome and potential impact of the new oral anticoagulants. Eur J Haematol 2012; 88: 185–94.
The SOX trial is the largest study so far of elastic compression stockings to prevent post-thrombotic syndrome.1 The post-thrombotic syndrome incidence using Ginsberg’s criteria was the primary endpoint and the Villalta’s criteria the secondary. Thus, the signs and symptoms of post-thrombotic syndrome were
left to the discretion of the observer with no quantitative measurement or use of CEAP (Clinical, Etiological, Anatomical, and Pathophysiological) classification. The results were not reported at 2 years as planned, but rather were a cumulative incidence of post-thrombotic syndrome from 6 to 24 months. There was no difference for both endpoints, with 2-year data for the primary outcome available in only 45·5% of patients, and for the secondary endpoint in 27% of patients. This study1 contradicts previous findings.2–4 The design and execution of this trial, including the timing of application of elastic compression stockings, the application itself, and definition and evaluation of compliance, seem inappropriate. Patients were randomised at a mean of 4·7 days from the time of deep venous thrombosis, and elastic compression stockings were applied within the first 2 weeks of diagnosis. What was the mean time from diagnosis to elastic compression stockings application? Optimum management in this acute phase is crucial for early symptom relief, recurrence, and late outcome. This has clearly been shown for adequate anticoagulation treatment,5 but also for compression and immediate mobilisation. 6 Compression and walking exercises reduce pain and swelling immediately, and symptoms diminish after 1 week.6 The aim of continuing wearing elastic compression stockings is to maintain this effect—this could be crucial because the patient might recognise the immediate benefit from using elastic compression stockings and therefore overall compliance would be improved. Sizing was based on leg measurements and elastic compression stockings were sent to patients without provision of proper training. Most patients are unable to apply stockings without specific instruments or training, especially
Life In View/Science Photo Library
that non-autonomous participants are identified, and as Malmqvist states, many potential participants are capable of fully understanding the risks and benefits of research. Malmqvist’s and Hunter’s arguments do not undermine the case for a right to participate in high-risk research.
129
I declare no competing interests.
David Shaw [email protected] Institute for Biomedical Ethics, University of Basel, CH-4056 Basel, Switzerland 1
Shaw D. The right to participate in high-risk research. Lancet 2014; 383: 1009–11.
Compression stockings to prevent postthrombotic syndrome
post-thrombotic syndrome: heparin, a drug discovered a century ago by Jay McLean (in 1916), which revolutionised deep-vein thrombosis prognosis.4 Moreover, a well-conducted anticoagulation treatment has also been associated with a decreased rate of post-thrombotic syndrome. Therefore, the results of the SOX trial should not be “leaving doctors empty handed”,2 but should rather reinforce their role in offering a high-quality anticoagulant treatment to their patients. An ongoing international placebocontrolled trial should assess more precisely the effect of heparin on the natural history of post-thrombotic syndrome after a distal deep-vein thrombosis (NCT00539058). The effect of new oral anticoagulants on the prevention of post-thrombotic syndrome is another important issue.5 We declare no competing interests.
In their SOX trial (March 8, p 880),1 Susan Kahn and colleagues did not report any benefit of elastic compression stockings in preventing post-thrombotic syndrome. According to Arina ten Cate-Hoek,2 this unexpected result “could have an important effect on daily practice, leaving doctors empty handed”.2 In 1946, in The Lancet, Swedish surgeon Gunnar Bauer reported on the effectiveness of heparin on long-term sequelae of deep-vein thrombosis.3 In the absence of anticoagulants, 5 years after an objectively confirmed “late” (ie, proximal) deep-vein thrombosis, all patients developed venous insufficiency and 20% a venous leg ulcer. Heparin reduced by 78·9% the risk of developing signs of post-thrombotic syndrome after deep-vein thrombosis.3 Interestingly, Bauer’s reported prevalence of post-thrombotic syndrome at 3 years in patients treated with heparin (up to 26·3%) did not differ substantially from the prevalence of post-thrombotic syndrome reported in contemporary cohorts. We therefore believe that doctors already have a very, although not fully, effective treatment to prevent www.thelancet.com Vol 384 July 12, 2014
*Jean-Philippe Galanaud, Marc Righini, Isabelle Quéré [email protected] Department of Internal Medicine and Clinical Investigation Centre, University Hospital Saint Eloi, Montpellier 34295, France (J-P G, IQ); and Vascular Medicine Unit, Geneva University Hospital, Geneva, Switzerland (MR) 1
2
3
4
5
Kahn SR, Shapiro S, Wells PS, et al. Compression stockings to prevent postthrombotic syndrome: a randomised placebocontrolled trial. Lancet 2014; 383: 880–88. Ten Cate-Hoek AJ. Elastic compression stockings—is there any benefit? Lancet 2014; 383: 851–53. Bauer G. Thrombosis; early diagnosis and abortive treatment with heparin. Lancet 1946; 247: 447–54. Galanaud JP, Laroche JP, Righini M. The history and historical treatments of deep vein thrombosis. J Thromb Haemost 2013; 11: 402–11. Prandoni P. Healthcare burden associated with the post-thrombotic syndrome and potential impact of the new oral anticoagulants. Eur J Haematol 2012; 88: 185–94.
The SOX trial is the largest study so far of elastic compression stockings to prevent post-thrombotic syndrome.1 The post-thrombotic syndrome incidence using Ginsberg’s criteria was the primary endpoint and the Villalta’s criteria the secondary. Thus, the signs and symptoms of post-thrombotic syndrome were
left to the discretion of the observer with no quantitative measurement or use of CEAP (Clinical, Etiological, Anatomical, and Pathophysiological) classification. The results were not reported at 2 years as planned, but rather were a cumulative incidence of post-thrombotic syndrome from 6 to 24 months. There was no difference for both endpoints, with 2-year data for the primary outcome available in only 45·5% of patients, and for the secondary endpoint in 27% of patients. This study1 contradicts previous findings.2–4 The design and execution of this trial, including the timing of application of elastic compression stockings, the application itself, and definition and evaluation of compliance, seem inappropriate. Patients were randomised at a mean of 4·7 days from the time of deep venous thrombosis, and elastic compression stockings were applied within the first 2 weeks of diagnosis. What was the mean time from diagnosis to elastic compression stockings application? Optimum management in this acute phase is crucial for early symptom relief, recurrence, and late outcome. This has clearly been shown for adequate anticoagulation treatment,5 but also for compression and immediate mobilisation. 6 Compression and walking exercises reduce pain and swelling immediately, and symptoms diminish after 1 week.6 The aim of continuing wearing elastic compression stockings is to maintain this effect—this could be crucial because the patient might recognise the immediate benefit from using elastic compression stockings and therefore overall compliance would be improved. Sizing was based on leg measurements and elastic compression stockings were sent to patients without provision of proper training. Most patients are unable to apply stockings without specific instruments or training, especially
Life In View/Science Photo Library
that non-autonomous participants are identified, and as Malmqvist states, many potential participants are capable of fully understanding the risks and benefits of research. Malmqvist’s and Hunter’s arguments do not undermine the case for a right to participate in high-risk research.
129
