Left Atrial Appendage Closure versus Oral Anticoagulation for Stroke Prevention in Atrial Fibrillation: Long-Term Outcomes from Four Randomized Trials

Left atrial appendage closure (LAAC) is primarily indicated for stroke prevention in atrial fibrillation (AF) patients who have contraindications to long-term oral anticoagulants (OACs). However, the long-term comparative benefits of LAAC versus OACs in the broader AF population remain unclear. To assess the long-term efficacy and safety of LAAC compared with OACs in patients with AF, we conducted a meta-analysis of randomized controlled trials (RCTs). We systematically searched PubMed, Embase, and Cochrane Library for eligible RCTs. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using fixed-effects models. Four RCTs involving 3,116 AF patients (1,736 assigned to LAAC and 1,380 to OACs) and follow-up durations ranging from 36 to 49.6 months were included. Compared with OACs, LAAC was associated with reduced risks of all-cause death (RR=0.78; 95% CI: 0.64-0.95) and cardiovascular or unexplained death (RR=0.69; 95% CI: 0.51-0.94). There were no significant differences between the two groups in stroke or systemic embolism, ischemic stroke or systemic embolism, and non-cardiovascular death. LAAC was associated with significantly lower risks of hemorrhagic stroke (RR=0.34; 95% CI: 0.16-0.76) and nonprocedural clinically relevant bleeding (RR=0.49; 95% CI: 0.40-0.61). Major bleeding (including procedural and nonprocedural) risk did not differ significantly between groups. In this meta-analysis of RCTs, LAAC was associated with significantly lower risks of all-cause and cardiovascular death, hemorrhagic stroke, and nonprocedural clinically relevant bleeding compared with OACs, without increasing the risk of thromboembolic events or major bleeding. These findings support the consideration of LAAC as an alternative to OAC in selected patients with AF.