Umbrella review of anticoagulation strategies for secondary prevention of cardioembolic stroke in atrial fibrillation: efficacy, safety, and knowledge gaps

Abstract

Atrial fibrillation (AF) is a major contributor to cardioembolic stroke. Anticoagulation, guided by CHA2DS2-VASc and HAS-BLED scores, is critical for secondary prevention, yet challenges persist in timing, patient-specific tailoring, and balancing efficacy with bleeding risk. This umbrella review synthesizes evidence on anticoagulation strategies for secondary prevention of cardioembolic stroke in AF patients. We searched PubMed, Scopus, Cochrane Library, Web of Science, and Embase for systematic reviews and meta-analyses (inception to May 2025) assessing oral anticoagulants (OACs) [vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs)] in AF patients with prior stroke or transient ischemic attack (TIA). Outcomes included recurrent stroke, systemic embolism, major bleeding, intracranial hemorrhage (ICH), and mortality. Quality was assessed using AMSTAR-2. Data were narratively synthesized, with quantitative metrics extracted where feasible. Eight reviews (2007-2025) were included, comprising 4-52 studies and 6893-94 656 participants. DOACs demonstrated superior efficacy over VKAs [apixaban odds ratio (OR) 0.79, 95% confidence interval (CI) 0.66-0.94], and VKAs outperformed antiplatelets (relative risk reduction 64%, absolute risk reduction 8.4%/year). DOACs showed lower major bleeding and ICH rates than VKAs, with apixaban exhibiting the most favorable safety profile (OR 0.71, 95% CI 0.61-0.81). Early versus delayed OAC initiation post-stroke improved efficacy (OR 0.68, 95% CI 0.55-0.84) with comparable safety. Identified knowledge gaps include optimal timing of OACs, outcomes in high-risk subgroups (elderly, renal impairment, and post-ICH), and cost-effectiveness. DOACs are superior to VKAs for secondary prevention of cardioembolic stroke in AF. However, individualized approaches are needed for timing and high-risk subgroups.