Studies comparing gender-specific outcomes in patients with
atrial fibrillation (AF) have reported conflicting results. Gender differences in
cerebrovascular accident/systemic
embolism (CVA/SE) or major
bleeding outcomes with novel oral
anticoagulant (
NOAC) use are not known. The goal of this analysis was to perform a systematic review and meta-analysis evaluating gender differences in residual risk of CVA/SE and major
bleeding outcomes in patients with nonvalvular AF treated with either
warfarin or
NOAC. Sixty-four randomized studies were identified using keywords "gender," "AF," and "CVA." Using the Preferred Reporting Items for Systemic Reviews and Meta-analysis method, 6 studies met criteria for inclusion in this meta-analysis. CVA/SE and major
bleeding outcomes were separately analyzed in cohorts receiving
warfarin and
NOAC agents, comparing men with women. Women with AF taking
warfarin were at a significantly greater residual risk of CVA/SE compared with men (odds ratio 1.279, 95% confidence interval 1.111 to 1.473, Z = -3.428, p = 0.001). No gender difference in residual risk of CVA/SE was noted in patients with AF receiving
NOAC agents (odds ratio 1.146, 95% confidence interval 0.97 to 1.354, p = 0.109). Major
bleeding was less frequent in women with AF treated with
NOAC. In conclusion, women with AF treated with
warfarin have a greater residual risk of CVA/SE and an equivalent major
bleeding risk, whereas those treated with
NOAC agents deemed superior to
warfarin are at equivalent residual risk of CVA/SE and less major
bleeding risk compared with men. These results suggest an increased net clinical benefit of
NOAC agents compared with
warfarin in treating women with AF.