New alternative anticoagulants in atrial fibrillation: the move beyond warfarin

Given the increasing prevalence of atrial fibrillation, the need for safe and effective stroke prophylaxis will continue to rise. Warfarin has been around for many years and has proven efficacy in preventing stroke, but it has major limitations due to its variable dosing, food and drug interactions, and requirement for regular monitoring. Newer agents which include dabigatran, rivaroxaban, and apixaban have recently or will soon be available and may provide an improved efficacy in stroke prevention, an improved safety profile, and improved user-friendliness. Dabigatran was the first of the agents to be widely available, and in the RE-LY study, dabigatran (150 mg dose) showed superiority to warfarin in preventing ischemic stroke and a significant reduction in intracranial bleeding. Rivaroxaban was studied in the ROCKETAF trial, and with once daily dosing, it showed noninferiority to warfarin in preventing stroke with a significant reduction in intracranial bleeding. The ARISTOTLE trial showed apixaban was superior to warfarin for stroke prevention, significantly reduced all major bleeding, and resulted in a significant reduction in all-cause mortality. While all three trials have important limitations, they were very large randomized trials with more than 14,000 patients each and show a clear overall net clinical benefit when compared with warfarin. Key features of the drugs as well as an individual's preferences and stability on warfarin will help guide the ultimate drug choice for any given patient, but these newer anticoagulant agents are likely to usher in a new era in stroke prevention in atrial fibrillation.