RESULTS: In comparison with men, women were older, had lower
body weight, were more likely to have
hypertension and renal dysfunction, but less likely to
smoke, drink alcohol, or have diabetes or
coronary artery disease. Pretreatment endogenous
factor Xa activity was significantly higher in women than in men (92.5% versus 86.1%, P<0.001). Treatment with
edoxaban in women resulted in greater peak
edoxaban concentration and inhibition of endogenous
factor Xa in comparison with men, resulting in similar endogenous
factor Xa activity between the sexes 2 to 4 hours after dose. Treatment with higher-dose
edoxaban regimen (versus
warfarin) resulted in similar reduction in the risk of
stroke/systemic embolic events (women: hazard ratio [HR], 0.87 [0.69-1.11], men: HR, 0.87 [0.71-1.06]; P-interaction=0.97) and major
bleeding (women: HR, 0.74 [0.59-0.92], men: HR, 0.84 [0.72-0.99]; P-interaction=0.34) in women and men. However, women assigned to higher-dose
edoxaban regimen experienced greater reductions in
hemorrhagic stroke (HR, 0.30 [95% CI, 0.15-0.59] versus HR, 0.70 [95% CI, 0.46-1.06]), intracranial
bleeding (HR, 0.20 [95% CI, 0.10-0.39] versus HR, 0.63 [95% CI, 0.44-0.89]), and life-threatening or fatal
bleeding (HR, 0.25 [95% CI, 0.15-0.42] versus HR, 0.72 [95% CI, 0.54-0.96]) than men (each P-interaction<0.05).
CONCLUSIONS: Despite many differences in baseline characteristics between women and men and higher baseline endogenous
factor Xa levels in women, the intensity of anticoagulation achieved with
edoxaban between the sexes was similar. Treatment with higher-dose
edoxaban regimen resulted in an even greater reduction in
hemorrhagic stroke and several serious
bleeding outcomes in women than in men, whereas the efficacy profile was similar between sexes.