Left atrial appendage closure versus medical therapy in atrial fibrillation: An updated meta-analysis of randomized trials on the trade-off between stroke prevention and bleeding

BACKGROUND: Long-term oral anticoagulation remains the standard of care for patients with atrial fibrillation, despite the non-negligible risk of bleeding. Percutaneous left atrial appendage closure (LAAC) has emerged as an alternative strategy for preventing stroke with inconclusive modern data. AIMS: Our aim was to evaluate the comparative efficacy and safety of LAAC vs. medical therapy in patients with atrial fibrillation. METHODS: A systematic search of PubMED, Scopus and EMBASE was conducted up to April 2026 to identify randomized controlled trials comparing LAAC with medical therapy. The primary endpoint was overall stroke. The secondary endpoints were ischemic stroke, hemorrhagic stroke, systemic embolism, mortality, major bleeding and non-procedural bleeding. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model with restricted maximum likelihood estimation and Hartung-Knapp adjustment. RESULTS: Six randomized controlled trials, encompassing 7004 patients globally (device group: 3681 patients; medical therapy group: 3323 patients), were included in the analysis. LAAC was associated with a similar risk of stroke to medical therapy (OR, 0.92; 95% CI, 0.65-1.3; P = 0.55) at a median 39 (interquartile range 36-47) months of follow-up. No significant differences were observed in ischemic stroke, hemorrhagic stroke, systemic embolism, all-cause mortality or cardiovascular mortality. Rates of major bleeding were comparable (OR, 1.13; 95% CI, 0.90-1.43; P = 0.23). However, medical therapy was associated with a significantly higher risk of non-procedural bleeding compared with LAAC (OR, 1.95; 95% CI, 1.67-2.27; P <0.001). These findings were consistent across subgroup analyses. CONCLUSIONS: LAAC provides thromboembolic protection comparable to medical therapy while reducing non-procedural bleeding. These findings support its role as an alternative strategy in selected patients at increased bleeding risk.