Predictors of ischemic stroke and major bleeding among patients with atrial fibrillation in clinical practice

BACKGROUND: Numerous risk scores exist to quantify the risk of ischemic stroke risk in patients with atrial fibrillation or flutter (AF/AFL). However, how these tools perform in cohorts or those already on oral anticoagulation (OAC) therapy is unclear. RESULTS: During the study period, 214,749 unique patients with AF/AFL were identified (DUHS-43,896 with median CHA₂DS₂-VASc score 3; PCORnet-170,853 with median CHA₂DS₂-VASc 3), of which 41.1% were not on OAC, 32.1% were on a direct oral anticoagulant (DOAC), and 26.8% were on warfarin. The CHA₂DS₂-VASc model alone demonstrated modest discrimination for ischemic stroke across OAC strategies (C-index range 64%-69%). Incorporation of routinely available clinical variables substantially improved discrimination for ischemic stroke (C-index 74%-76% for no OAC, 74%-75% for DOAC, and 70%-72% for warfarin) and for major bleeding (C-index 75%-76% for no OAC, 75%-76% for DOAC, and 72%-73% for warfarin). Several factors not captured by CHA₂DS₂-VASc, including race and prior major bleeding, were independently associated with ischemic stroke risk. CONCLUSIONS: The CHA₂DS₂-VASc score provides modest discrimination for ischemic stroke and major bleeding across AF/AFL populations, including patients already treated with OAC. Incorporation of routinely available clinical factors substantially improves risk discrimination and highlights important sources of residual risk not captured by existing models.