Meta-analysis of gender differences in residual stroke risk and major bleeding in patients with nonvalvular atrial fibrillation treated with oral anticoagulants

Am J Cardiol. 2014 Feb 1;113(3):485-90. doi: 10.1016/j.amjcard.2013.10.035. Epub 2013 Nov 11.


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.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / complications
  • Atrial Fibrillation / drug therapy*
  • Female
  • Global Health
  • Hemorrhage / epidemiology*
  • Hemorrhage / etiology
  • Hemorrhage / prevention & control
  • Humans
  • Incidence
  • Male
  • Prognosis
  • Risk Factors
  • Sex Distribution
  • Sex Factors
  • Stroke / epidemiology*
  • Stroke / etiology
  • Stroke / prevention & control


  • Anticoagulants