Abstract Body (Do not enter title and authors here): Introduction: Clinical trials comparing anticoagulation (AC) therapy with left atrial appendage closure (LAAC) in patients with atrial fibrillation (AF) have shown conflicting results regarding stroke, bleeding, and mortality outcomes. This meta-analysis aims to clarify these discrepancies, with a specific focus on ischemic stroke or systemic embolism, major bleeding, cardiovascular mortality, and all-cause mortality.

Methods: We searched PubMed and ClinicalTrials.gov for randomized controlled trials (RCTs) using the terms atrial fibrillation, left atrial appendage closure, anticoagulation, stroke, and major bleeding. Additionally, reference lists from the retrieved studies were reviewed to identify other eligible trials. Four RCTs were identified and included in the meta-analysis.

Results: This meta-analysis included 3,116 patients with AF, comprising 1,736 patients in the LAAC group and 1,380 in the AC group. The incidence of ischemic stroke or systemic embolism was comparable between the two groups, with a relative risk (RR) of 1.25 (95% confidence interval [CI]: 0.85–1.83). Although the rate of major bleeding was lower in the LAAC group, the difference was not statistically significant (RR: 0.81; 95% CI: 0.65 to 1.02). In contrast, cardiovascular mortality (RR: 0.67; 95% CI: 0.49 to 0.92) and all-cause mortality (RR: 0.78; 95% CI: 0.64 to 0.96) were significantly reduced in the LAAC group.

Conclusions: In patients with AF, LAAC demonstrates a similar risk of ischemic stroke or systemic embolism compared to AC. While major bleeding appears less frequent with LAAC, the difference is not statistically significant. Notably, LAAC is associated with significantly lower cardiovascular and all-cause mortality. Further long-term and real-world studies are needed to better understand the long-term outcomes of both treatment strategies.