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European Heart Journal Advance Access originally published online on December 19, 2007
European Heart Journal 2008 29(2):155-165; doi:10.1093/eurheartj/ehm575
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org

New oral anticoagulants in atrial fibrillation

Alexander G.G. Turpie*

Department of Medicine, HHS-General Hospital, 237 Barton Street East, Hamilton, Ontario, Canada L8L 2X2

Received 19 April 2007; revised 7 November 2007; accepted 14 November 2007; online publish-ahead-of-print 19 December 2007.

*Corresponding author. Tel: +1 905 528 9946, Fax: +1 905 521 1551. Email: turpiea{at}mcmaster.ca

Atrial fibrillation (AF) is a major risk factor for stroke. Currently, acetylsalicylic acid (a platelet inhibitor) and vitamin K antagonists (VKAs; oral anticoagulants), including warfarin, are the only approved antithrombotic therapies for stroke prevention in patients with AF. Although effective, VKAs have unpredictable pharmacological effects, requiring regular coagulation monitoring and dose adjustment to maintain effects within the therapeutic range. The clinical development pathway for novel anticoagulants often involves evaluation of efficacy and safety in a short-term indication, such as the prevention of venous thrombo-embolism (VTE), followed by longer-term VTE treatment studies, and finally chronic indications, including stroke prevention studies in patients with AF. The coagulation pathway provides many targets for novel anticoagulants, including Factor Xa (FXa) and Factor IIa (thrombin). Numerous oral, direct FXa inhibitors are in various stages of clinical development, including rivaroxaban, LY517717, YM150, DU-176b, apixaban, and betrixaban, and are anticipated to overcome the limitations of VKAs. Dabigatran is the only oral direct thrombin inhibitor in late-stage development. Studies of these agents for stroke prevention in patients with AF are planned or ongoing. If approved, they may represent the next generation of anticoagulants, by providing new therapeutic options for stroke prevention in patients with AF.

Key Words: Anticoagulant • Atrial fibrillation • Factor Xa inhibitor • Direct thrombin inhibitor • Stroke


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