Sulodexide given after 3 to 12 months of oral anticoagulation significantly reduced the risk of recurrent venous thromboembolism compared to placebo (HR 0.49; 95% CI 0.27-0.92; P=0.02).
RCT (n=615)
double-blind
randomly assigned
Yes
Does sulodexide reduce recurrence of venous thromboembolism in patients with first-ever unprovoked venous thromboembolism who had completed 3 to 12 months of oral anticoagulant treatment?
Sulodexide given after discontinuation of initial anticoagulant treatment significantly reduces the risk of recurrent unprovoked venous thromboembolism without increasing bleeding risk.
Effect estimate: HR 0.49 (95% CI 0.27-0.92)
Absolute Event Rate: 4.9% vs 9.7%
p-value: p=0.02
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. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrialsregister.eu/. Identifier: EudraCT number 2009-016923-77.
Andreozzi et al. (Sat,) conducted a rct in first-ever unprovoked venous thromboembolism (n=615). sulodexide vs. placebo was evaluated on recurrence of venous thromboembolism (HR 0.49, 95% CI 0.27-0.92, p=0.02). Sulodexide given after 3 to 12 months of oral anticoagulation significantly reduced the risk of recurrent venous thromboembolism compared to placebo (HR 0.49; 95% CI 0.27-0.92; P=0.02).