Modification of outcomes with aspirin or apixaban in relation to female and male sex in patients with atrial fibrillation: a secondary analysis of the AVERROES study.

The main objective of the present analysis was to assess the effect of treatment with aspirin compared with apixaban on ischemic stroke and major bleeding in women compared with men. Female patients with atrial fibrillation are at increased stroke risk compared with male patients, and the underlying reasons for higher risk are uncertain. Ancillary analysis of the Apixaban Versus Acetylsalicylic Acid [ASA] to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial, comparing aspirin and apixaban, focused on sex differences. Mean follow-up was 1.1 years. Women compared with men tended to be older (aspirin, 71.8 versus 68.8 years; apixaban, 71.4 versus 68.6 years), with a higher proportion of those aged≥75 years. Also, women had less peripheral artery disease (aspirin, 2.4% versus 3.7%; apixaban, 1.4% versus 3.0%), more heart failure, and higher mean CHADS2 (congestive heart failure, hypertension, age of 75 years or older, diabetes [1 point each], stroke or transient ischemic attack [2 points]) scores (aspirin, 2.2 versus 2.0; apixaban, 2.1 versus 2.0). Women compared with men had higher ischemic stroke rates (aspirin, 3.99% versus 2.28%; apixaban, 1.55% versus 0.82%) but similar bleeding rates (aspirin, 1.29% versus 1.22%; apixaban, 1.15% versus 1.36%). The relative effect of apixaban compared with aspirin was similar in men and women for both ischemic stroke (women, 3.99% versus 1.55%; hazard ratio, 0.39; 95% confidence interval, 0.23-0.64; men, 2.28% versus 0.82%; hazard ratio, 0.36; 95% confidence interval, 0.19-0.63; Pint=0.84) and major bleeding (women, 1.29% versus 1.15%; hazard ratio, 1.15; 95% confidence interval, 0.59-2.23; men, 1.36% versus 1.22%; hazard ratio, 1.13; 95% confidence interval, 0.64-2.02; Pint=0.96). Female patients with atrial fibrillation had higher ischemic stroke rates compared with male patients, but the relative effects of apixaban compared with aspirin on both ischemic stroke and bleeding were similar in men and women.