Sex-related differences in clinical characteristics, treatment and outcomes in patients with atrial fibrillation and acute ischemic stroke treated with non-vitamin-K antagonists

Summary. Background and aim. Women with atrial fibrillation (AF) are typically older at stroke onset and are reported to have worse outcomes. We aimed to investigate sex-related differences in clinical characteristics, outcomes (ischemic events, major bleeding, disability, mortality), and non-vitamin K oral anticoagulant (NOAC) management following ischemic stroke. Methods. We analyzed data from the RAF-NOAC registry, evaluating 90-day rates of ischemic events, major bleeding, disability (modified Rankin Scale >2), and mortality. Multivariable logistic regressions were used to assess associations between sex and outcomes, adjusting for age, baseline National Institutes of Health Stroke Scale (NIHSS), and NOAC dosing. Results. Of 1,127 patients with acute ischemic stroke and AF, 53.4% were females. Females were significantly older (77.6±9.1 vs 73.2±10.3 years, p <0.001) and had more severe strokes (NIHSS 8±6 vs 7±6, p = 0.01). No differences were observed in time to NOAC initiation (12.2±12.1 vs 12.6±13.5 days, p = 0.537), but females more frequently received low-dose NOACs (45% vs 35.0%, p = 0.001). No significant sex-related differences emerged in ischemic events (2.6% vs 2.1% in females; 3.3% vs 3.2% in males for low- vs full-dose), hemorrhagic events (1.9% vs 2.4% in females; 2.2% vs 2.9% in males), disability (mRS >2 occurred in 59% of females vs 41% of males), or mortality (15 vs 11 deaths, respectively). Sex was not independently associated with any outcome after adjustment. NIHSS independently predicted both disability (OR=1.17, 95% CI 1.14-1.20) and mortality (OR=1.13, 95% CI 1.07-1.19), while age was independently associated with disability only (OR=1.03, 95% CI 1.02-1.05). Conclusions. In this prospective registry, sex was not independently associated with 90-day outcomes. Although females more frequently received low-dose NOACs, this was not linked to significant differences in safety or efficacy. While this prescribing pattern may reflect appropriate clinical decisions, such as older age, impaired renal function or lower weight, our findings underline the importance of further investigation into sex-related treatment differences and adherence to individualized, evidence-based anticoagulation strategies.