Rivaroxaban for atrial fibrillation patients

Rivaroxaban for atrial fibrillation patients

Rivaroxaban (Xarelto), Janssen Pharmaceutical's once-a-day oral Xa inhibitor, has been approved for reducing the risk of stroke in patients with atrial fibrillation. The drug was previously approved for prophylaxis of deep vein thrombosis in patients undergoing hip or knee replacement. Rivaroxaban is the second "non-warfarin" oral anticoagulant to be approved for this indication after the direct thrombin inhibitor dabigatran (Pradaxa). The approval was based on the ROCKET AF trial, a double-blind, randomized, noninferiority comparative trial with warfarin, which showed a rate of stroke or systemic embolism of 2.1% per year for rivaroxaban and 2.4% per year for warfarin. The study looked at 14,000 patients over 700 days of follow-up. Rates of major and non-major bleeding were the same with the two drugs, although the rate of intracranial hemorrhage was lower for rivaroxaban while the rate of GI bleeding was lower with warfarin. ROCKET AF showed noninferiority of rivaroxaban vs warfarin but not superiority (N Engl J Med 2011;365:883-891). The approval sets up a major marketing showdown between Janssen and Boehringer Ingelheim, the manufacturer of dabigatran, for this multibillion dollar market. Meanwhile, Pfizer and Bristol-Myers Squibb are jointly developing a third drug — apixaban, also a factor Xa inhibitor — which is undergoing an "accelerated review" by the FDA with approval likely in March 2012. All three drugs have the potential disadvantage of the lack of an antidote, a problem that seems to be plaguing dabigatran with more than 250 fatal bleeding episodes reported worldwide since the drug was approved in 2010. A recent report suggests that prothrombin complex concentrate may be an effective reversal agent for rivaroxaban but not dabigatran (Circulation 2011;124:1573-1579).