Combined Oral Anticoagulant and Antiplatelet for Atrial Fibrillation and Cerebral Atherosclerosis: A Meta-Analysis.

Background and Purpose: Patients with ischemic stroke with both atrial fibrillation (AF) and large artery atherosclerosis (LAA) represent therapeutic challenges, and the optimal antithrombotic regimen remains uncertain. We conducted a meta-analysis comparing oral anticoagulant (OAC) monotherapy with OAC plus antiplatelet therapy in this population. Methods: PubMed and EMBASE were searched through June 30, 2025, for studies enrolling patients with ischemic stroke and evidence of both AF and LAA. Outcomes included recurrent ischemic stroke, major bleeding, all-cause mortality, and a composite outcome. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the Peto method, with random-effects sensitivity analyses, stratified by short-term (<3 months) and long-term (≥1 year) follow-up. Results: Eight cohort studies were analyzed. In the short-term, combination therapy was associated with a reduced risk of recurrent ischemic stroke (OR, 0.37; 95% CI, 0.14-0.97; P=0.043), without a significant increase in major bleeding, although this association did not persist under random-effects sensitivity analysis (OR, 0.37; 95% CI, 0.13-1.07; P=0.067). Conversely, long-term combination therapy was associated with higher risks of major bleeding (OR, 1.25; 95% CI, 1.08-1.45; P=0.002), all-cause mortality (OR, 1.25; 95% CI, 1.01-1.54; P=0.039), and composite outcome (OR, 1.49; 95% CI, 1.27-1.74; P<0.001), without reducing recurrent ischemic stroke (OR, 1.12; 95% CI, 1.00-1.26; P=0.054). Conclusions: While long-term OAC plus antiplatelet therapy increases bleeding risk without preventing recurrent stroke, short-term combination therapy may offer benefits in selected patients with concomitant LAA, though this early efficacy signal should be interpreted with caution.