EINSTEIN Studies Support Oral Rivaroxaban for VTE

December 4, 2010—The EINSTEIN study investigators published findings online ahead of print in the New England Journal of Medicine on rivaroxaban, an oral factor Xa inhibitor, that may provide a simple, fixed-dose regimen for treating acute deep vein thrombosis (DVT) and for continued treatment without the need for laboratory monitoring.

Bayer AG (Leverkusen, Germany) sponsored and directed the studies. Bayer developed rivaroxaban, which it manufactures and markets outside of the United States as Xarelto. Ortho-McNeil, a division of Johnson & Johnson's Ortho-McNeil-Janssen Pharmaceuticals, Inc. (Raritan, NJ), collaborated with Bayer on the studies. Ortho-McNeil will market rivaroxaban in the United States if the drug is approved by the US Food and Drug Administration.

The investigators conducted EINSTEIN-DVT, an open-label, randomized, event-driven, noninferiority study, which compared oral rivaroxaban alone (15 mg twice daily for 3 weeks followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT.

In parallel, the investigators carried out the EINSTEIN-Extension study, which was a double-blind, randomized, event-driven superiority trial that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism (VTE). The primary efficacy outcome for both studies was recurrent VTE. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial treatment study and major bleeding in the continued treatment study.

As detailed in the New England Journal of Medicine, the study of rivaroxaban for acute DVT included 3,449 patients: 1,731 were given rivaroxaban and 1,718 were given enoxaparin plus a vitamin K antagonist. The investigators found that rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%] vs 51 events with enoxaparin and vitamin K antagonist [3%]; hazard ratio, 0.68; 95% confidence interval, 0.44–1.04; P < .001). The principal safety outcome occurred in 8.1% of the patients in each group.

In the continued treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%] vs 42 with placebo [7.1%]; hazard ratio, 0.18; 95% confidence interval, 0.09–0.39; P < .001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%) versus none in the placebo group (P = .11), reported the EINSTEIN investigators.

The investigators concluded that rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of VTE that may improve the benefit-to-risk profile of anticoagulation.