Combined antithrombotic therapy vs. oral anticoagulation alone for ischemic stroke with concomitant atrial fibrillation and large artery atherosclerosis: a systematic review and meta-analysis.

Treating ischemic stroke patients who have both nonvalvular atrial fibrillation (NVAF) and large artery atherosclerosis (LAA) presents a clinical challenge. It remains unclear whether adding antiplatelet therapy (APT) to oral anticoagulation (OAC) reduces stroke risk or only increases the danger of hemorrhage. We conducted a systematic review and meta-analysis of randomized and observational studies to compare OAC monotherapy against combined therapy (OAC + APT) in patients with recent ischemic stroke, NVAF, and LAA. PubMed, Embase, Scopus, Cochrane Library, and Web of Science were searched from inception to December 2025. We applied random-effects models to estimate Risk Ratios (RR). Seven studies comprising 14,884 patients were included. Combined therapy was not associated with a significant reduction in recurrent ischemic stroke (RR 0.98; 95% CI: 0.92-1.04; p = 0.55) or all-cause mortality (RR 1.11; 95% CI: 0.98-1.26; p = 0.09) compared to OAC monotherapy. Conversely, the combined strategy was associated with a statistically significant increase in the risk of major bleeding (RR 1.49; 95% CI: 1.04-2.15; p = 0.03). Our findings indicate that adding antiplatelets to anticoagulation in patients with stroke, AF, and LAA confers no real clinical benefit but significantly exacerbates hemorrhagic morbidity. Consequently, OAC monotherapy should remain the standard of care, while combined therapy should be avoided in routine practice.