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

Background 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 thromboembolism (STE), and the predictive performance of CHA₂DS₂-VASc vs. CHA₂DS₂-VA scores. Methods We analyzed data from a European prospective cohort. The association between female sex and OAC prescription was assessed in patients with CHA₂DS₂-VA score ≥1. We analyzed the residual STE risk in OAC-treated patients and compared the predictive performance of CHA₂DS₂-VASc and CHA₂DS₂-VA scores. Results Among 10,080 patients (41.8% women; mean age 69.7 [SD 10.7] 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 (ie. negative) reclassification compared to CHA₂DS₂-VASc (net reclassification index -0.088, 95% CI -0.164 to -0.001), with no significant differences in discrimination or net benefit. Conclusions 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 to CHA₂DS₂-VASc.