A Comparison of Edoxaban and Warfarin for Symptomatic VTE

Although warfarin remains the standard therapy for venous thromboembolism (VTE), recent studies have identified other effective agents, including direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban and apixaban). This manufacturer-sponsored, double-blind, noninferiority trial assessed the efficacy and safety of another factor Xa inhibitor, edoxaban, for patients with symptomatic deep venous thrombosis, pulmonary embolism, or both.

A total of 8240 patients (mean age, 56; 57% men, 60% with deep venous thromboembolism only and 40% with pulmonary embolism) were randomized to receive either warfarin adjusted to an INR of 2.0 to 3.0 or edoxaban (60 mg orally once daily, or 30 mg daily for those with creatinine clearance of 30–50 mL/min) in addition to initial heparin therapy. Among the exclusion criteria were severely reduced renal function (creatinine clearance <30 mL/min) or the need for antiplatelet therapy. Therapy was continued for 3 to 12 months at the discretion of the treating physician. The time in therapeutic range in the warfarin group was 63.5%.

At 1 year, the primary efficacy endpoint of adjudicated recurrent VTE occurred in 3.2% of patients receiving edoxaban and 3.5% of those receiving warfarin (hazard ratio, 0.89; P for noninferiority, <0.001). This endpoint occurred significantly less often with edoxaban therapy in the subgroup of patients with pulmonary embolus and evidence of right ventricular dysfunction. The safety endpoint of major or clinically relevant non-major bleeding occurred significantly less often with edoxaban therapy than with warfarin (8.5% vs. 10.3% of patients; HR=0.81, P for superiority, 0.004), driven primarily by differences in non-major bleeding. Other adverse events were similar between the two therapies.