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

Recurrent VTE particularly after an unprovoked VTE event is common and risk remains high for many years with approximately 20% of patients having a recurrence within 2 years after discontinuation of treatment with a vitamin K antagonist (Schulman S et al, N Engl J Med 1995;332:1661-5). Risk of recurrence can be decreased with continued warfarin administration but at an increased risk of bleeding. New non-VKA oral anticoagulants for extended duration treatment have an efficacy noninferior to VKA and generally decreased rates of bleeding. Sulodexide is a glycosaminoglycan with anti-thrombotic and profibrinolytic activities (Coccheri S et al, Drug Des Devel Ther 2014;8:49-65) and is associated with negligible bleeding risk (Errichi BM et al, Angiology 2004;55:243-9). Pharmacological and clinical profiles suggest Sulodexide may have a role in prevention of recurrent VTE following discontinuation of oral anticoagulation. The aim of this trial was to verify the efficacy and safety of Sulodexide in prevention of recurrent VTE after the end of VKA treatment in patients with a first unprovoked VTE. This was a multicenter, double-blind study of 615 patients with a first ever unprovoked VTE who had completed 3-12 months of oral anticoagulant treatment. Patients were randomly assigned to Sulodexide lipasemic units twice daily or placebo for 2 years in addition to elastic stockings. Primary efficacy outcome was recurrence of VTE. Major or clinically relevant bleeding was the primary safety outcome. VTE recurred in 15 of 307 patients who received Sulodexide and in 30 of 308 patients who received placebo (HR, 0.49; 95% CI, 0.27-0.92; P = .02). An analysis in which lost to follow-up was assigned to failure yielded a risk ratio among the treated to control subjects of 0.54 (95% CI, 0.35-0.85; P = .009). There were no major bleeding episodes. Two patients in each group had a clinically relevant bleeding episode and adverse events were similar in the two groups.