Gender Effect in the Efficacy and safety of Direct Oral Anticoagulants (DOACs) - Systematic Review and Meta-Analysis of Randomized Trials

Background: Despite their effectiveness in the reduction of stroke risk in both men and women, vitamin K antagonists (VKA) are underutilized in the treatment of AF, and women with AF are less likely to be prescribed VKA as compared to men. Thus, ischemic stroke rates remain higher and VKA use rates lower for women as compared to men with AF. DOACs have emerged as an alternative to VKA in atrial fibrillation (AF). However the efficacy and safety of DOACs in women as compared to men have not been determined.

Objectives: to assess the safety and efficacy of DOACSs in women compared to men.

Methods: MEDLINE, EMBASE, Cochrane, and the Clinical Trials Registry (ClinicalTials.gov) were searched for randomized clinical trials up to Nov 2015. The data were pooled using random-effects models

Results: 11 trials met inclusion criteria. Among 98,996 patients 38.5% were women. Overall there was no difference in the relative risk (RR) of major bleeding in women compared to men (RR, 1.02; 95% CI, 0.82–1.28), DOACs were associated with a decreased risk for major bleeding compared to VKA in both women (RR, 0.81; 95% CI, 0.68 -0.96, I²=72%) and men (RR, 0.82; 95% CI, 0.72 -0.94, I=68%). DOACs exhibited greater efficacy compared to VKA in both women and men, and were associated with a lower risk for primary efficacy outcomes (RR, 0.84; 95% CI, 0.75-0.95; I²=8%, RR, 0.89; 95% CI, 0.81 -0.97; I²=0%, respectively). There was no difference in efficacy in women compared to men (RR, 1.11; 95% CI 0.99–1.24)

Conclusion: In pooled analysis, the safety and efficacy of DOACs did not differ according to gender. DOACs were associated with reduced risk for major bleeding and enhanced efficacy in both women and men, compared to VKA.