Marc Fisher MD Kennedy Lees MD Section Editors: Atrial fibrillation (AF) remains a prominent cause of ischemic stroke worldwide. The incidence of AF increases with age and prevalence reaches 10% in octogenarians.1 The proportion of strokes attributable to this common arrhythmia will continue to rise as our population ages. In the Framingham Study, almost one fourth of all strokes that occurred in patients aged >80 years were attributable to AF.2 Furthermore, cerebral infarctions in patients with AF tend to be larger than strokes caused by most other etiologies and result in high rates of both disability and mortality.3 In use for >50 years, the anticoagulant warfarin was first shown to prevent stroke in patients with AF 2 decades ago. A series of randomized trials demonstrated an exceptional level of efficacy (relative risk reductions close to 70%) for prevention of ischemic stroke and surprisingly low rates of intracerebral hemorrhage or major systemic bleeding.4 Despite this remarkable performance in clinical trials and strong endorsement by international guidelines, both physicians and patients have been reluctant to embrace warfarin therapy in AF. Underuse is typically attributed to the inconvenience of coagulation monitoring, complexities associated with drug and dietary interactions as well as the perception that hemorrhage rates may have been underestimated in the clinical trials. It is estimated that only approximately half of warfarin-eligible patients with AF actually receive anticoagulation.5 Furthermore, even those who are treated are often not maintained in the therapeutic range. This is due in part to warfarin’s nonlinear pharmacokinetics, but also its interaction with multiple other hepatically metabolized drugs and dietary intake of vitamin K that competes with warfarin’s synthetic inhibition of vitamin K-dependent clotting …