Atrial fibrillation and female sex: use of oral anticoagulants in a large European cohort and residual risk of thromboembolism and stroke

Aims The role of female sex in stroke risk and oral anticoagulant (OAC) use in atrial fibrillation (AF) remains controversial. This study evaluates sex-specific differences in OAC prescription, residual risk of stroke/TIA and systemic thromboembolism (STE), and the predictive performance of CHA2DS2-VASc vs. CHA2DS2-VA scores. Methods and results We analysed data from a European prospective cohort. The association between female sex and OAC prescription was assessed in patients with CHA2DS2-VA score ≥ 1. We analysed the residual STE risk in OAC-treated patients and compared the predictive performance of CHA2DS2-VASc and CHA2DS2-VA scores. Among 10 080 patients [41.8% women; mean age 70.1 (SD 10.0) years] with CHA2DS2-VA ≥1, women had higher burden of comorbidities and less likely to receive OACs than men (OR 0.79, 95% CI: 0.69–0.90). In OAC-treated patients, STE rates were higher in women (IR 1.33 vs. 0.94 per 100 person–years). After adjusting for confounders and the competing risk of death, female sex was not statistically significantly associated with an increased risk of STE (sHR 1.24, 95% CI 0.89–1.74, P = 0.210). CHA2DS2-VA and CHA2DS2-VASc scores had similar predictive performance (AUC 0.603 vs. 0.605, P = 0.665). CHA2DS2-VA showed worse (i.e. negative) reclassification compared with CHA2DS2-VASc (net reclassification index −0.088, 95% CI −0.164 to −0.001), with no significant differences in discrimination or net benefit. Conclusion In AF patients treated with OAC, the increased residual risk of STE associated with female sex was non-significant after adjusting for confounders and the competing risk of death. Both scores had similar predictive performance but CHA2DS2-VA showed worse reclassification compared with CHA2DS2-VASc.