Sulodexide for the Prevention of Recurrent Venous Thromboembolism: The SURVET Study: A Multicenter, Randomized, Double-Blind, Placebo Controlled Trial

Background —Patients with a first episode of unprovoked venous thromboembolism have a high risk of recurrence after discontinuation of the anticoagulant therapy. Extending anticoagulation reduces the risk of recurrence but is associated with increased bleeding. Sulodexide, a glycosaminoglycan, exerts antithrombotic and profibrinolytic actions, with low bleeding risk when administered orally, but its benefit for preventing recurrent venous thromboembolism is poorly 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=0.025). The analysis assigning lost to follow-up to failure, yielded a risk ratio among treated vs. controls of 0.54 (95% CI: 0.35-0.85; P=0.009). No major bleeding episodes occurred; two patients in each treatment group had a clinically relevant bleeding episode. Adverse events were similar in the two groups. Conclusions —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. Clinical Trial Registration Information —http://www.clinicaltrialsregister.eu/. Identifier: EudraCT number 2009-016923-77.