1. ARISTOTLE Objectives Primary: test for noninferiority of apixaban, a novel oral direct factor Xa inhibitor, versus warfarin Secondary: test for superiority of apixaban with respect to the primary outcome and to the rates of major bleeding and death from any cause Study Design Randomized, multicenter, double-blind, double-dummy 18,201 patients with AF and at least one additional risk factor for stroke, randomized to treatment with apixaban or warfarin Primary Outcome Ischemic or hemorrhagic stroke or systemic embolism Primary Safety Outcome Rate of major ISTH bleeding

2. ARISTOTLE Summary of Results As compared to warfarin, treatment with apixaban in patients with AF and at least one additional risk factor for stroke: – reduces stroke and systemic embolism by 21% – reduces major bleeding by 31% – reduces mortality by 11% Consistent effects across all major subgroups and with fewer study drug discontinuations on apixaban

3. ARISTOTLE

4. Conclusions In patients with atrial fibrillation, apixaban is superior to warfarin in preventing stroke or systemic embolism, causes less bleeding, and results in lower mortality ARISTOTLE