Clinical characteristics and outcomes of ischemic stroke despite appropriate oral anticoagulation for atrial fibrillation: A systematic review and meta-analysis of real-world studies

Background: Despite appropriate oral anticoagulants (OACs) use to prevent cardioembolism in atrial fibrillation (AF) and thromboembolic conditions, some patients still experience ischemic stroke. Objectives: This systematic review and meta-analysis aimed to investigate clinical characteristics and outcomes of ischemic stroke occurring despite appropriate OACs use for atrial fibrillation, comparing direct oral anticoagulants (DOACs) with vitamin K antagonists (VKAs). Methods: A systematic search of PubMed and Scopus identified observational cohort studies published in English until October 2, 2024, on ischemic stroke patients on appropriate OAC doses. We utilized random-effects modeling to assess the impact of stroke severity, anticoagulant type, and revascularization on in-hospital mortality, 90-day functional recovery (modified Rankin Scale [mRS] 0–2), 90-day stroke recurrence, and intracranial hemorrhage (ICH). Results: Out of 25,985 articles screened, 11 studies (14 cohorts) involving 10,624 patients were included. The mean age was 76 years, with median National Institute of Health Stroke Scale (NIHSS) score of 5.1. Prevalent risk factors included hypertension (78.3%), dyslipidemia (44.3%), and prior stroke or TIA (55.6%). No significant baseline differences were found by OAC type, except for higher coronary heart disease prevalence in the VKA group. DOAC patients showed better 90-day functional outcomes than VKA patients (60.4% vs. 35.7%; p = 0.048). Meta-regression did not identify significant predictors for in-hospital death or 90-day favorable outcomes. Conclusions: Ischemic stroke patients despite OACs exhibited a high burden of vascular risk factors and moderate stroke severity. DOAC-related strokes showed better 90-day functional outcomes than those on VKA. Further research on long-term prognosis is needed.