ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) was a randomized, double- blind trial comparing apixaban (5 mg twice daily) versus warfarin (target international normalized ratio, 2.0 3.0) in 18201 patients with AF and at least 1 additional risk factor for stroke (mean CHADS2 score 2.1). Women constituted one third (35.3%) of participants. The primary outcome was isch- emic or hemorrhagic stroke or systemic embolism.391,391a ROCKET AF (Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) was a double-blind trial that randomly assigned 14264 patients with nonvalvular AF who were at increased risk for stroke to receive either rivaroxaban (20 mg daily) or dose-adjusted warfarin. Women represented 39.7% of the participants. The primary end point was stroke or systemic Of note, the risk of stroke was greater among participants in ROCKET AF than in RELY or ARISTOTLE, because the mean CHADS2 score was 3.47, with no patients in the lowest categories. Although all 3 trials using new oral anti- coagulants consistently showed a greater number of events per year among women, none demonstrated a differential benefit by sex for the primary or secondary outcomes (P value for the interaction was not significant).391 393 These results should be interpreted with caution, because none of these studies were powered to determine a sex difference in the efficacy of new oral anticoagulants over warfarin. In addition, women with AF had on average 30% higher concentrations of dabigatran than their male counterparts for the same given dose. The effect is most likely attributable to the average 30% lower creatinine clearance in women. 