Sulodexide for the Prevention of Recurrent Venous Thromboembolism

T he risk of recurrence of venous thromboembolism (VTE) persists for many years after anticoagulant treatment is withdrawn 1 and is particularly high among patients with unprovoked VTE. 2 About 20% of patients have a recurrence within 2 years after discontinuation of treatment with a vitamin K antagonist (VKA). 3–6 Extending the treatment with VKA reduces the risk of recurrence but increases the risk of Background—Patients with a first episode of unprovoked venous thromboembolism have a high risk of recurrence after discontinuation of anticoagulant therapy. Extending anticoagulation reduces the risk of recurrence but is associated with increased bleeding. Sulodexide, a glycosaminoglycan, exerts antithrombotic and profibrinolytic actions with a low bleeding risk when administered orally, but its benefit for preventing recurrent venous thromboembolism is not well known. Methods and Results—In this multicenter, double-blind study, 615 patients with first-ever unprovoked venous thromboembolism who had completed 3 to 12 months of oral anticoagulant treatment were randomly assigned to sulodexide 500 lipasemic units twice daily or placebo for 2 years, in addition to elastic stockings. The primary efficacy outcome was recurrence of venous thromboembolism. Major or clinically relevant bleeding was the primary safety outcome. Venous thromboembolism recurred in 15 of the 307 patients who received sulodexide and in 30 of the 308 patients who received placebo (hazard ratio, 0.49; 95% confidence interval [CI], 0.27–0.92; P=0.02). The analysis in which lost to follow-up was assigned to failure yielded a risk ratio among treated versus control subjects of 0.54 (95% confidence interval, 0.35–0.85; P=0.009). No major bleeding episodes occurred; 2 patients in each treatment group had a clinically relevant bleeding episode. Adverse events were similar in the 2 groups. Conclusion—Sulodexide given after discontinuation of anticoagulant treatment reduced the risk of recurrence in patients with unprovoked venous thromboembolism, with no apparent increase of bleeding risk. bleeding, as well as the inconvenience and costs of laboratory monitoring and dose adjustments. The effects of the newer non-VKA oral anticoagulants for therapy of acute VTE events 9–12 and for extended treatment to avoid recurrences 13,14 have recently been investigated by a number of clinical trials that, as a whole, showed an efficacy noninferior to VKA and rates of bleeding in general inferior to VKA, especially for extended treatment. Sulodexide is a natural glycosaminoglycan with anti-thrombotic and profibrinolytic activities 15 that can be administered orally or parenterally and affects the normal hemostasis to a lower extent than heparin with a very …