Sex-related difference in bleeding and thromboembolic risks in patients with atrial fibrillation treated with direct oral anticoagulants

Background: Sex-related difference in non-valvular atrial fibrillation (NVAF) patients treated with direct oral anticoagulants (DOACs) is still to be investigated. We aimed to investigate sex difference in patient characteristics and clinical outcomes of the NVAF patients treated with DOAC in the real-world Japanese clinical practice. Methods and results: We conducted a single-center prospective observational registry of NVAF patients treated with DOACs: the DIRECT registry (women, N = 806; men, N = 1410; follow-up duration, 407 +/- 388 days). In the present study, all patients were stratified by sex. Women had significantly higher age, lower body weight, lower hemoglobin, lower creatinine clearance, and a higher bleeding risk estimate (ORBIT score) and higher thromboembolic risk estimates (CHADS(2) score and CHA(2)DS(2)VAS score) than men. Albeit the different bleeding risk estimates by the ORBIT score between both sexes, the Kaplan-Meier estimates of bleeding events were similar between both sexes (Log-rank test P = 0.152 for clinically significant bleeding, and P = 0.122 for major bleeding). The Kaplan-Meier estimated 2 year rate of stroke/systemic embolism was higher in women than in men (4.9 +/- 1.3% vs. 2.3 +/- 0.6%, Log-rank test P = 0.048). Conclusions: Our real-world study of patients treated with DOAC showed that Japanese women experienced comparable bleeding events as compared to men despite the higher bleeding risk estimates. The higher thromboembolic risk estimates in women than in men translated into the higher thromboembolic event rates. Clinical trials identifier: UMIN000033283