Pooled Efficacy and Safety of Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulants or Antiplatelets: A Meta-Analysis of the Landmark Randomized Trials.

Landmark randomized controlled trials (RCTs) comparing left atrial appendage occlusion (LAAO) against direct oral anticoagulants (DOACs) are individually underpowered for small but clinically meaningful differences. We performed a pooled meta-analysis to provide more precise efficacy and safety data. Utilizing random-effects models, we pooled data from 5890 patients across four landmark RCTs (PRAGUE-17, CLOSURE-AF, OPTION, and CHAMPION-AF) at their longest follow-up. There were no significant differences between LAAO and antithrombotics in cardiovascular mortality (5.3% vs. 4.8%, p = 0.33), all-cause stroke (3.3% vs. 2.8%, p = 0.31), systemic embolism (0.2% vs. 0.1%, p = 0.68), or major bleeding (6.6% vs. 6.8%, p = 0.85). Non-procedural bleeding was significantly lower with LAAO (9.2% vs. 16.7%; RR 0.55; 95% CI 0.47-0.64; p < 0.0001), though there was a numerical trend toward more ischemic stroke events (2.7% vs. 2.0%; RR 1.35; 95% CI 0.97-1.88; p = 0.08). LAAO offers similar overall efficacy and safety to modern antithrombotics. It represents a clinical trade-off: accepting a known upfront procedural risk for a robust, long-term reduction in non-procedural bleeding, potentially at the cost of a slight numerical increase in ischemic stroke.