Meta-Analysis of Gender Differences in Residual Stroke Risk and Major Bleeding in Patients With Non-Valvular Atrial Fibrillation Treated With Oral Anticoagulants

Study Questions:

What is the effect of gender on residual risk of cerebrovascular accident/systemic embolism (CVA/SE) and major bleeding outcomes in patients with nonvalvular atrial fibrillation (AF) treated with either warfarin or novel oral anticoagulants (NOACs)?


Sixty-four randomized studies were identified using keywords “Gender,” “AF,” and “CVA.” Using the PRISMA method, six 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 to women. A pooled analysis of gender differences in major bleeding, defined using International Society of Thrombosis and Hemostasis (ISTH) definition, was performed for the cohorts treated with warfarin and NOAC agents deemed superior to warfarin.


Women with AF on warfarin were at a significantly higher residual risk of CVA/SE compared to men (odds ratio [OR], 1.279, 95% confidence interval [CI], 1.111-1.473; Z = -3.428; p = 0.001). No gender difference in residual risk of CVA/SE was noted in AF patients receiving NOAC agents (OR, 1.146; 95% CI, 0.97-1.354; p = 0.109). Major bleeding was less frequent in women with AF treated with NOAC.


The authors concluded that women with AF treated with warfarin have a higher residual risk of CVA/SE and an equivalent major bleeding risk, whereas those treated with NOAC agents are at equivalent residual risk of CVA/SE and a lower major bleeding risk when compared to men.


This study suggests that women with AF, ordinarily at a higher risk of CVA/SE, continue to have an outcome disadvantage when treated with warfarin prophylaxis, with smaller 'net clinical benefit' compared to men. If treated with NOAC agents deemed superior to warfarin, this outcome disadvantage compared to men disappears, and a larger net clinical benefit is expected, in view of equivalent efficacy in preventing CVA/SE and lower incidence of major bleeding. NOACs appear to be the preferred agents in treating women with AF, but additional prospective validation is indicated.

Clinical Topics: Anticoagulation Management

Keywords: Odds Ratio, Risk, Stroke, Thrombosis, Warfarin, Confidence Intervals, Embolism, Hemostasis, Hemorrhage

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