Rivaroxaban: an oral, factor Xa inhibitor

Rivaroxaban is an oral, direct factor Xa inhibitor that is approved in several countries for the prevention of venous thromboembolism (VTE) after orthopedic surgery. It is currently being evaluated by the FDA for this indication. Based on the findings of the EINSTEIN study, it appears the drug is also effective for the treatment of acute deep vein thrombosis (DVT). EINSTEIN consists of three randomized trials of rivaroxaban, one for the treatment of acute DVT, one for treatment of acute pulmonary embolism, and one for continued, long-term treatment in patients who have received treatment for acute DVT or pulmonary emboli. The results of the first and third wings of the study were recently reported in the New England Journal of Medicine.

In the DVT treatment arm, 3449 patients with acute DVT were randomized to rivaroxaban (50 mg twice daily for 3 weeks, followed by 20 mg once daily) or subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months. In the continued treatment wing of the study, patients were randomized in a double-blind fashion to rivaroxaban 20 mg once daily or placebo for additional 6 or 12 months after completion of 6-12 months of treatment for VTE. The primary outcome for both studies was recurrent DVT. For the treatment of acute DVT, rivaroxaban was non-inferior to enoxaparin-vitamin K antagonist (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.44-1.04; P < 0.001). In the continued treatment study, rivaroxaban had superior efficacy compared to placebo (8 events [1.3%] vs 42 events [7.1%] with placebo; HR 0.18; 95% CI, 0.09-0.39; P < 0.001). There were four patients in the rivaroxaban group with non-fatal major bleeding vs none in the placebo group. The EINSTEIN authors concluded that "Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation" (N Engl J Med 2010;363:2499-2510).

Rivaroxaban is also being evaluated for the prevention of stroke in patients with nonvalvular atrial fibrillation based on the ROCKET AF study, which was presented at the American Heart Association meetings in November 2010. If approved, it will join the recently approved direct thrombin inhibitor dabigatran (Pradaxa®) for this indication. Both drugs have the advantage over warfarin of not requiring ongoing lab monitoring.