Development and External Validation of the GLORIA-AF Bleeding Weighted Risk Score for Patients with Atrial Fibrillation.
AIMS Major bleeding remains a major barrier to optimal anticoagulation in patients with atrial fibrillation (AF). We aimed to develop and externally validate a weighted score that balances simplicity and prediction for 1-year major bleeding prediction. METHODS Using prospective multinational GLORIA-AF Phase II/III data, we developed the GLORIA-AF Bleeding Weighted Risk Score using LASSO-penalized regression with stability selection, coefficient-rescaling and internal validation. The score was externally evaluated in EORP-AF and APHRS-AF registries. Discrimination, calibration and clinical benefit were assessed using C-index, observed-to-expected ratio, calibration plot and decision-curve analysis, and compared with HAS-BLED, unweighted GLORIA-AF score and full multivariable Cox model. RESULTS Among 20,250 eligible derivation cohort patients (69.9 [10.3] years; 9,092 female [44.9%]), 317 (1.6%) had major bleeding during 1-year follow-up. The derived score ranges from 0 to 22, with the highest weight (5) assigned to age >65 years, followed by abnormal kidney function (3). The derived score achieved C-index of 0.688 (95% CI: 0.660-0.717), outperforming HAS-BLED (C-index: 0.631, 95% CI: 0.604-0.658; P < 0.001), while preserving discrimination comparable to full multivariable regression (C-index: 0.690; 95%CI: 0.661-0.719; P = 0.084). Calibration was good (O:E ratio: 0.996) and DCA showed greater net benefit than HAS-BLED across 1% to 3% thresholds. Among 9,752 external validation patients, 148 (1.5%) had major bleeding. The derived score achieved C-index of 0.674 (95% CI: 0.643-0.705; P < 0.001), with better discrimination, calibration and clinical benefit than HAS-BLED. CONCLUSIONS The GLORIA-AF Bleeding Score showed modestly higher discrimination than HAS-BLED for 1-year major bleeding prediction while retaining clinical interpretability and usability. External validation in independent European and Asia-Pacific registries further supports its transportability beyond the derivation population.