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Randomized Controlled Trial
. 2015 Nov 17;132(20):1891-7.
doi: 10.1161/CIRCULATIONAHA.115.016930. Epub 2015 Sep 25.

Sulodexide for the Prevention of Recurrent Venous Thromboembolism: The Sulodexide in Secondary Prevention of Recurrent Deep Vein Thrombosis (SURVET) Study: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Giuseppe M Andreozzi  1 , Angelo A Bignamini  2 , Giovanni Davì  2 , Gualtiero Palareti  2 , Jiří Matuška  2 , Martin Holý  2 , Katarzyna Pawlaczyk-Gabriel  2 , Andrej Džupina  2 , German Y Sokurenko  2 , Yury P Didenko  2 , Laurentia D Andrei  2 , Gianfranco Lessiani  2 , Adriana Visonà  2 ; SURVET Study Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Sulodexide for the Prevention of Recurrent Venous Thromboembolism: The Sulodexide in Secondary Prevention of Recurrent Deep Vein Thrombosis (SURVET) Study: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Giuseppe M Andreozzi et al. Circulation. .

Abstract

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.

Keywords: glycosaminoglycans; randomized controlled trial; recurrence; venous thromboembolism.

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Figures

Figure 1.
Figure 1.
Enrollment and randomization. VTE indicates venous thromboembolism.
Figure 2.
Figure 2.
Risk of recurrence of venous thromboembolism in patients randomly assigned to sulodexide or placebo. A, Cumulative risk of recurrent venous thromboembolism. B, Results of an analysis of risk after adjustment for age, sex, index event (pulmonary embolism, or deep vein thrombosis), duration of anticoagulant therapy, and time from completion of anticoagulation therapy to randomization.
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