Arrhythmias and Conduction Disturbances
Meta-Analysis of Gender Differences in Residual Stroke Risk and Major Bleeding in Patients With Nonvalvular Atrial Fibrillation Treated With Oral Anticoagulants

https://doi.org/10.1016/j.amjcard.2013.10.035Get rights and content

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.

Section snippets

Methods

Using the keywords “atrial Fibrillation,” “gender,” “anti-coagulation,” and “outcomes,” we searched indexed studies recorded in major databases including PubMed, EMBASE, Cochrane Library, and Google Scholar. The method outlined in the Preferred Reporting Items for Systemic Reviews and Meta-analysis document was used.14 A total of 452 relevant studies were identified on search using these databases and reviewed independently by 4 investigators to check if they met inclusion criteria. We included

Results

A total of 6 studies met inclusion criteria.15, 16, 17, 18, 19, 20 Baseline characteristics of patients from the included trials are listed in Table 1.

Five studies15, 16, 17, 18, 19 reporting gender-specific annualized event rates of CVA/SE in patients with AF treated with warfarin prophylaxis were included in the first analysis. The pooled sample consisted of 26,260 patients, with 16,760 men and 9,500 women. A total of 478 men (2.85%) and 349 women (3.67%) developed CVA/SE. The forest plot

Discussion

The results of our meta-analysis indicate that women with AF have a significantly greater residual risk of CVA/SE when treated using warfarin prophylaxis compared with men. The gender difference disappears when a similar analysis is performed on a pooled population treated with NOACs found to be superior to warfarin, in published randomized trials. Coincidentally, these NOACs found superior to warfarin are the agents approved by Food and Drug Administration for use in the United States.

Gender

Disclosures

The authors have no conflicts of interest to disclose.

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