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(Circulation. 2007;116:449-455.)
© 2007 American Heart Association, Inc.

New Drugs and Technologies

Challenges of Establishing New Antithrombotic Therapies in Atrial Fibrillation

Stuart J. Connolly, MD, FRCPC; John Eikelboom, MBBS, MSc, FRACP, FRCPA; Martin O’Donnell, MB, MRCPI; Janice Pogue, MA, MSc; Salim Yusuf, DPhil, FRCPC

From the Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

Correspondence to Dr Stuart Connolly, 237 Barton St East, Suite 504, Hamilton, Ontario, Canada L8L 2X2. E-mail connostu@phri.ca

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Warfarin is the single most effective treatment to prevent stroke in patients with atrial fibrillation (AF) in that it reduces the risk by about two thirds compared with placebo.¹ Despite its effectiveness, however, warfarin is difficult to use and its uptake into clinical practice has been constrained.² Warfarin has a slow onset and offset of action, it exhibits considerable variability in dose response among individuals, it is subject to multiple food and drug interactions, it has a narrow therapeutic window, and considerable risk of hemorrhage exists. The slow offset of action of warfarin can be beneficial if a patient misses a dose but complicates temporary discontinuation of warfarin for surgery. Thus, warfarin requires careful laboratory monitoring and dose adjustment to maintain the international normalized ratio (INR) in the target therapeutic range. Even with careful laboratory monitoring, major bleeding occurs in 1% to 3% of AF patients on warfarin per year. Consequently, many clinicians and patients are reluctant to use warfarin. Some patients have contraindications to anticoagulation, but others choose not to use it.² Such patients typically use aspirin.

Educational and support programs have been shown to improve knowledge of disease and treatment, INR control, and physician management of AF.^3–5 Nonetheless, there have been intensive efforts to find a replacement for warfarin. Several new drugs with the potential to overcome the limitations of warfarin have been evaluated in randomized trials but appeared to be less effective or less safe than warfarin. The experience from these trials has highlighted the methodological challenges . . . [Full Text of this Article]

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