Is Left Atrial Appendage Closure a Universal Alternative to NOACs? A Meta-Analysis of NOAC-Era Trials

Background Non-vitamin K antagonist oral anticoagulants (NOACs) are the guideline-recommended standard for stroke prevention in atrial fibrillation (AF), yet bleeding risks limit real-world adherence. Percutaneous left atrial appendage closure (LAAC) offers a mechanical alternative without definitive comparative synthesis. Objectives To evaluate percutaneous LAAC versus NOAC therapy by synthesizing all contemporary NOAC-era randomized controlled trials (RCTs). Methods Five databases and registries (PubMed, MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov) were searched from inception to 8 May 2026 for RCTs comparing percutaneous LAAC against NOACs in adults with non-valvular AF. Risk of bias was assessed using Cochrane RoB 2. Ischemic stroke was pooled using a random-effects DerSimonian-Laird model; primary efficacy composite and non-procedural bleeding were evaluated via pre-specified narrative synthesis. Results Four RCTs (CHAMPION-AF, OPTION, PRAGUE-17, CLOSURE-AF) comprising 5,890 patients were included. LAAC achieved noninferiority for the primary efficacy composite in three trials and demonstrated a statistically significant 45-56% reduction in non-procedural bleeding across the three moderate-risk trials. CLOSURE-AF did not meet noninferiority but retained a directionally consistent bleeding reduction. Pooled ischemic stroke analysis (HR 1.31; 95% CI 0.96-1.80; I^2=0%) showed no statistically significant increase in stroke risk, though a consistent directional trend toward more ischemic events was observed. Conclusions LAAC significantly reduces non-procedural bleeding in moderate-risk AF patients, though this benefit attenuates in very high-risk populations. A consistent, statistically nonsignificant ischemic stroke trend and population-dependent efficacy establish LAAC as a shared decision-making alternative to NOACs rather than a universal replacement, pending 5-year CHAMPION-AF data.