Left Atrial Appendage Closure vs Direct Oral Anticoagulants in Atrial Fibrillation

BACKGROUND: Left atrial appendage closure (LAAC) is a potential alternative to oral anticoagulation for stroke prevention in atrial fibrillation. OBJECTIVES: We performed an updated meta-analysis of randomized controlled trials comparing LAAC with direct oral anticoagulants (DOACs) for efficacy and safety. METHODS: We systematically searched from January 1, 2012, to April 3, 2026, for randomized controlled trials comparing percutaneous LAAC with DOACs in patients with atrial fibrillation. Using the longest available follow-up from each trial, we pooled efficacy and bleeding outcomes, including stroke, death, and intracranial hemorrhage (ICH), and pooled relative risks (RRs) with random-effects models. RESULTS: Four randomized trials involving 5,890 patients were included, with 2,949 assigned to LAAC and 2,941 to DOAC therapy. The median follow-up ranged from 36 to 42 months. There were no significant differences in all stroke, hemorrhagic stroke, systemic embolism, all-cause death, or cardiovascular death. LAAC was associated with a numerically higher risk of ischemic stroke (RR: 1.36; 95% CI: 0.99-1.89; P = 0.06), which became significant (RR: 1.45; 95% CI: 1.03-2.06; P = 0.03) after exclusion of the OPTION trial. LAAC significantly reduced all nonmajor (RR: 0.53; 95% CI: 0.40-0.71; P < 0.0001) and nonprocedure-related major (RR: 0.79; 95% CI: 0.65-0.97; P = 0.02) and nonmajor bleeding (RR: 0.47; 95% CI: 0.39-0.57; P < 0.0001), whereas risks of all major bleeding (RR: 0.97; 95% CI: 0.81-1.17; P = 0.77) and ICH (RR 0.76; 95% CI: 0.45-1.26; P = 0.28) were similar. CONCLUSIONS: Compared with DOACs, LAAC reduced nonprocedure-related major and nonmajor bleeding, potentially at the cost of an increased risk of ischemic stroke, without significant differences in major bleeding or ICH.