Left Atrial Appendage Occlusion versus Oral Anticoagulation in Atrial Fibrillation: A Meta-Analysis of Randomized Trials

BACKGROUND: Emergence of direct oral anticoagulants as the first-line therapy for stroke prevention in nonvalvular atrial fibrillation has redefined the comparator benchmark for left atrial appendage occlusion (LAAO). OBJECTIVES: The objective of the study was to compare the efficacy and temporal safety of LAAO vs oral anticoagulation (OAC). METHODS: Randomized trials of LAAO vs OAC in nonvalvular atrial fibrillation were pooled for incidence rate ratios (IRRs) per patient-year; key endpoints were assessed with trial sequential analysis (TSA) and Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: Across 6 trials (N = 7,004), LAAO vs OAC was associated with higher ischemic stroke (130 vs 76 events; IRR: 1.43; 95% CI: 1.07-1.91; P = 0.01; number needed to harm: 101; GRADE: low); however, this was sensitive to individual trial exclusion and TSA indicated insufficient information (41% of required size). All-cause stroke (152 vs 114; IRR: 1.11; 95% CI: 0.86-1.43; P = 0.43) and all-cause mortality (403 vs 368; IRR: 0.93; 95% CI: 0.78-1.10; P = 0.39) were comparable. Total major bleeding did not differ (IRR: 0.91; P = 0.29), but LAAO significantly reduced nonprocedural major bleeding (194 vs 232; IRR: 0.71; 95% CI: 0.55-0.91; P = 0.01; number needed to treat: 19; GRADE: high) and clinically relevant nonmajor bleeding (145 vs 303; IRR: 0.48; 95% CI: 0.39-0.58; P < 0.001; number needed to treat: 15). CONCLUSIONS: LAAO significantly reduces nonprocedural major bleeding (TSA-confirmed) and clinically relevant nonmajor bleeding vs OAC. A trend toward higher ischemic stroke was not TSA-confirmed and was sensitive to trial exclusion; all-cause stroke and mortality were similar. These findings quantify the benefit-harm tradeoff central to LAAO decisions.