Even though many patients with deep vein thrombosis (DVT) are told to wear compression stockings for two years to prevent complications, a Dutch study suggests they may get the same results in half the time.
All of the patients in the study wore compression stockings for six months to treat what’s known as deep vein thrombosis (DVT), which is when clots develop in a major vein, usually in the lower leg or thigh. Patients often develop what’s known as post-thrombotic syndrome, a constellation of symptoms that include pain, swelling, sores and skin damage. After that initial six months of treatment, researchers randomly assigned 428 people to wear compression stockings for a total of two years, the current standard of care. Another 437 patients could stop wearing stockings sooner, often within just six months, based on doctors’ assessments of their risk of complications.
Overall, 28% of the people assigned to wear compression stockings for two years developed post-thrombotic syndrome, as did 29% of the patients in the group that could halt treatment sooner. This difference was too small to rule out the possibility that it was due to chance.
“It is possible to restrict compression to only six months on an individualised basis in those that do not experience complications,” said lead study author Dr Arina J ten Cate-Hoek of Maastricht University Medical Centre in the Netherlands. “This is positive for patients because this means that only those who need compression for longer duration will prolong therapy,” ten Cate-Hoek said. “For the others, shorter duration of therapy means less hassles and less restrictions in their daily living.”
Overall, two-thirds of the people in the individualised therapy group stopped wearing compression stockings before two years. About 55% of them stopped after six months, and another 11% stopped after one year.
By the end of the study, 125 people in the individualised therapy group developed post-thrombotic syndrome, as did 118 people in the standard two-year treatment group. A total of 24 patients died, including 17 on individualised therapy, but none of the fatalities were treatment-related, researchers report.
The study wasn’t designed to test whether compression stockings might work better than other interventions, and it’s not clear why more patients died in the individualised therapy group, the authors note.
Once patients develop post-thrombotic syndrome, however, treatment options are scarce, said Dr Dinanda Kolbach, a researcher at Huidcentrum Limburg in Maastricht who wasn’t involved in the study. “Preventive therapy with elastic compression stockings has been the cornerstone of treatment for decades,” Kolbach said. “However, the optimum duration of treatment after the acute phase (beyond the first six months) of deep vein thrombosis was uncertain.”
The study results suggest that most patients can wear these for less than two years without an increased risk of complications, said Dr Menno Huisman, a researcher at Leiden University Medical Centre in the Netherlands.
“This is very important for patients, because wearing compression stockings – which is unpractical, cumbersome and expensive – can be restricted to around 40% of patients needing this prolonged therapy,” Huisman, who wasn’t involved in the study, said. “For the other 60% a shorter duration means less restrictions.”
Background: Therapy with elastic compression stockings has been the cornerstone for prevention of post-thrombotic syndrome for decades in patients after acute deep venous thrombosis. It is uncertain who benefits most from therapy, and what the optimum duration of therapy should be. We therefore aimed to assess the safety and efficacy of individualised duration of compression therapy versus the standard duration of 24 months following an initial treatment period of 6 months.
Methods: We did a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial at 12 hospitals in the Netherlands and two in Italy. We randomly assigned patients (1:1) with acute proximal deep vein thrombosis of the leg and without pre-existent venous insufficiency (Clinical Etiological Anatomical and Pathophysiological score <C3) to receive either individualised duration of elastic compression therapy or standard duration of therapy for 24 months following an initial treatment period of 6 months. Randomisation was done with a web-based automatic randomisation programme (TENALEA) and a random block size (2–12), and was stratified by centre, age, and body-mass index. In the initial phase, compression was applied within 24 h of diagnosis according to three prespecified protocols. All patients received elastic compression stockings (30–40 mm Hg) for 6 months, and were instructed to wear them every day during ambulant hours. Thereafter treatment was tailored on the basis of clinical signs and symptoms scored according to the Villalta post-thrombotic syndrome scale; patients assigned to individualised therapy with two consecutive Villalta scores of 4 or less were instructed to stop using the stockings. Patients were followed up for 2 years and assessed at five clinic visits at study inclusion, and 3, 6, 12, and 24 months after diagnosis (stocking allocation was not revealed to the assessors). The primary outcome was the proportion of patients with post-thrombotic syndrome at 24 months diagnosed according to original Villalta criteria (a score of ≥5 on two consecutive occasions at least 3 months apart) assessed by intention to treat. The predefined non-inferiority margin for the difference in success rates was set at 7·5%. This study has been completed and is registered with ClinicalTrials.gov, number NCT01429714.
Findings: Between March 22, 2011, and July 1, 2015, we enrolled 865 patients and randomly assigned 437 to individualised duration compression stockings and 428 to standard duration. 283 (66%) of 432 patients in the intervention group were advised before 24 months to stop wearing elastic compression stockings (236 [55%] of 432 patients after 6 months, and 47 [11%] of 432 at 12 months). Post-thrombotic syndrome occurred in 125 (29%) of 432 patients receiving individualised duration of therapy and in 118 (28%) of 424 receiving standard duration of therapy (odds ratio for difference 1·06, 95% CI 0·78 to 1·44). The absolute difference was 1·1% (95% CI −5·2 to 7·3), thus meeting the non-inferiority margin. 24 patients died, 17 (4%) in the individualised treatment group and seven (2%) in the standard duration group, but no deaths were related to treatment. No serious adverse events related to the intervention occurred.
Interpretation: Individualised therapy with elastic compression stockings for the prevention of post-thrombotic syndrome was non-inferior to standard duration of therapy of 24 months. Individualising the duration is effective and could shorten the length of therapy needed, potentially enhancing patients’ wellbeing.
Arina J ten Cate-Hoek, Elham E Amin, Annemieke C Bouman, Karina Meijer, Lidwine W Tick, Saskia Middeldorp, Guy J M Mostard, Marije ten Wolde, Simone M van den Heiligenberg, Sanne van Wissen, Marlène HW van de Poel, Sabina Villalta, Erik H Serné,
Hans-Martin Otten, Edith H Klappe, Ingrid M Bistervels, Mandy N Lauw, Margriet Piersma-Wichers, Paolo Prandoni, Manuela A Joore, Martin H Prins, Hugo ten Cate