Dabigatran: comparison to warfarin, pathway to approval, and practical guidelines for use

Abstract

Atrial fibrillation (AF) affects more than 3 million Americans and is expected to reach epidemic proportions as the US population ages. The presence of AF increases lifetime stroke risk nearly 5-fold. Conventionally, patients at moderate or high risk of stroke have been prescribed antiplatelet agents or vitamin K antagonists to reduce the risk, but each has significant limitations. Accordingly, the development of new oral anticoagulants (direct thrombin inhibitors [DTIs] and factor Xa inhibitors) has attracted significant interest. The DTI dabigatran etexilate was recently shown to provide superior risk reduction to warfarin for stroke and systemic embolism for patients with nonvalvular AF and recently gained US Food and Drug Administration approval for this indication. Dabigatran etexilate is the first new agent for this indication in the United States in more than 50 years. Herein, we outline the options for stroke prevention in AF in the new oral anticoagulant era. The efficacy and practical obstacles surrounding the use of warfarin are summarized. We then review the mechanism of action, efficacy, and safety of dabigatran-including clinically relevant pharmacokinetics. Practical issues of initiation, conversion of anticoagulant therapy, and recommendations for dabigatran use in patients at high risk of bleeding and other special populations are discussed. We conclude by proposing a role for dabigatran in the armamentarium of drugs available for the management of stroke risk in AF.