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.