Sex differences in stroke risk assessment and severity after removal of female sex from clinical scoring: a prospective cohort study

Background: The 2024 ESC atrial fibrillation guidelines introduced the CHA₂DS₂-VA score, eliminating female sex as an independent risk criterion for stroke risk stratification. This revision aimed to improve clarity and avoid sex-based overtreatment. However, its real-world impact on women with ischemic stroke remains unclear. Methods: In a prospective cohort of 714 consecutive stroke patients, 161 (22.5%) had documented atrial fibrillation. Risk stratification was performed using both CHA₂DS₂-VASc and the revised CHA₂DS₂-VA score. Stroke severity and functional outcome were analyzed by sex. Propensity score matching and multivariable logistic regression were used to examine the independent association between sex and stroke severity. Results: Female patients with atrial fibrillation were older and had a higher vascular risk burden than men. They presented with significantly more severe strokes (median NIHSS 12 vs. 8; P < 0.01) and tended toward worse outcomes. After score recalibration, 11 of 81 women (13.6%) had a CHA₂DS₂-VA score ≤1, falling below the European Society of Cardiology anticoagulation threshold—despite having experienced an ischemic stroke. Most of these patients had cardioembolic strokes and moderate-to-severe neurological deficits. In matched analyses, female sex remained independently associated with severe stroke (aOR 1.54, 95% CI 1.03–2.29). Conclusion: The removal of female sex from the CHA₂DS₂-VA score does not eliminate sex-specific disparities in stroke risk. A clinically meaningful subgroup of women now falls below treatment thresholds, raising concern for under-treatment. Women present significantly more disabilities and neurological deficits after stroke. These findings call for nuanced anticoagulation strategies that go beyond score-based decisions and better reflect real-world risk in female stroke patients with atrial fibrillation.