Posterior versus anterior circulation infarct location and outcomes after breakthrough ischemic stroke in orally anticoagulated patients for atrial fibrillation: An ASPERA-R inverse probability-weighted analysis

Introduction and aims: Breakthrough ischemic stroke may occur despite ongoing oral anticoagulation (OAC) in patients with atrial fibrillation (AF). Whether infarct location influences prognosis remains unclear. We aimed to compare clinical characteristics and outcomes of posterior versus anterior circulation infarct (PCI vs ACI). Methods: Multicentre retrospective analysis from the ASPERA cohort, including patients with AF and ischemic stroke despite continuous OAC (Feb. 2020 to Feb. 2025). Patients were classified as PCI or ACI according to infarct location. The primary outcome was a 90-day composite of recurrent ischemic stroke, myocardial infarction, or vascular death. Secondary outcomes included modified Rankin Scale (mRS) shift and all-cause mortality. Safety outcomes included 24-h hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH), 90-day ICH. Inverse-probability weighting with truncation of extreme weights and additional adjustment for residual imbalance were applied. Results: Among 1649 patients (mean age 78.0 ± 10.7 years; 47.8% men), 165 (10.0%) had PCI. PCI patients were more often on vitamin K antagonists and had lower stroke severity. After weighting, PCI was associated with a higher risk of the composite outcome (aHR 1.50, 95% CI 1.19-1.90; p < 0.001), vascular death (aHR 1.46, 95% CI 1.12-1.91; p = 0.005), all-cause mortality (aHR 1.85, 95% CI 1.51-2.27; p < 0.001), and worse mRS shift (aOR 1.79, 95% CI 1.51-2.13; p < 0.001). PCI was also associated with an increased risk of ICH (aHR 2.25, 95% CI 1.08-4.70; p = 0.031), whereas 24-HT and sICH were similar between groups. Conclusions: In AF patients with breakthrough stroke on OAC, PCI identifies a subgroup with worse 90-day outcomes. These findings support the prognostic relevance of infarct location.