Female Sex, Time in Therapeutic Range, and Clinical Outcomes in Atrial Fibrillation Patients Taking Warfarin

BACKGROUND AND PURPOSE: Female patients have higher risk for stroke than male patients in nonanticoagulated atrial fibrillation patients, but limited data are available on sex differences in stroke and bleeding outcomes among patients with anticoagulated atrial fibrillation on warfarin, especially in relation to quality of anticoagulation control, as reflected by the time in therapeutic range (TTR). METHODS: We investigated adverse outcomes in females (n=791) and males (n=1501) among 2292 patients with atrial fibrillation taking warfarin arm in the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial. RESULTS: The combined end point of cardiovascular death and stroke/systemic embolism (SSE) was similar in females versus males. There was no sex differences in either cardiovascular death or SSE. Compared with males, females had a lower risk of major bleeding (hazard ratio, 0.39; 95% confidence interval, 0.18-0.87; P=0.02). No differences were seen in mortality and stroke outcomes between females and males either in the prespecified age subgroups or in relation to TTR categories. TTR was negatively correlated with any clinically relevant bleeding in both females (r=-0.86; P=0.03) and males (r=-0.94; P=0.005). On Cox regression, TTR (but not female sex) emerged as an independent predictor for combined cardiovascular death/SSE and clinically relevant bleeding events. CONCLUSION: Anticoagulated female patients with atrial fibrillation had a similar rate of cardiovascular death and SSE, but a lower risk of major bleeding, compared with males. TTR (but not female sex) was an independent predictor for combined cardiovascular death and SSE and clinically relevant bleeding events.