2010 - Rivaroxaban was noninferior to enoxaparin for preventing short-term recurrent VTE and superior to placebo in continued treatment.

Question What are the efficacy and safety of short-term and continued rivaroxaban for preventing recurrent proximal deep venous thrombosis (DVT)? Methods Design 2 randomized controlled trials (Acute DVT Study and Continued Treatment Study [EINSTEIN-Extension]). ClinicalTrials.gov NCT00440193 and NCT00439725. Allocation Concealed.* Blinding Blinded (patients, clinicians, and {data collectors}† [Continued Study only]; outcome adjudicators).* Follow-up period Acute Study: 3, 6, or 12 months. Continued Study: 6 or 12 months. Setting Acute Study: 244 centers from 31 countries. Continued Study: 172 centers from 28 countries. Patients Acute Study: 3449 adults (mean age 56 y, 57% men) with acute, symptomatic, objectively confirmed proximal DVT without symptomatic pulmonary embolism (PE). Exclusion criteria included é>48 hours of therapeutic anticoagulation; é>1 dose of a vitamin K antagonist (VKA); and treatment with thrombectomy, fibrinolysis, or a vena cava filter. Continued Study: 1197 patients (mean age 58 y, 58% men) with symptomatic, objectively confirmed DVT or PE who had been treated for 6 to 12 months with a VKA or rivaroxaban, and for whom there was equipoise regarding need for continued anticoagulation. Exclusion criteria for both studies included another indication for a VKA; creatinine clearance <>30 mL/min; active or high risk for bleeding; uncontrolled hypertension; and use of strong cytochrome P-450>3A4 inhibitors. Intervention Acute Study: oral rivaroxaban, 15 mg twice daily for 3 weeks and then 20 mg/d for 3, 6, or 12 months (n =>1731); or standard therapy of subcutaneous enoxaparin followed by VKA to maintain an INR of 2.0 to 3.0 (n =>1718). Continued Study: rivaroxaban (n =>602), 20 mg once daily, or matching placebo (n =>595), for 6 or 12 months. Outcomes Symptomatic recurrent venous thromboembolism (VTE; DVT or PE). Other outcomes included a composite of recurrent VTE or major bleeding. Safety outcomes were clinically relevant bleeding (Acute Study) or major bleeding (Continued Study). Patient follow-up >99% (intention-to-treat analysis). Main results The main results are in the Table. Rivaroxaban did not differ from enoxaparin for clinically relevant bleeding (Acute Study: 8.1% vs 8.1%, P =>0.77) or from placebo for major bleeding (Continued Study: 4 vs 0 patients, P =>0.11). Conclusions In patients with proximal deep venous thrombosis, short-term rivaroxaban was noninferior to enoxaparin and vitamin K antagonists for preventing recurrent venous thromboembolism. Continued treatment with rivaroxaban decreased recurrent venous thromboembolism compared with placebo. [ABSTRACT FROM AUTHOR]