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

ABSTRACT 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; I²=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. CONDENSED ABSTRACT This meta-analysis of four randomized controlled trials (5,890 patients) compared percutaneous left atrial appendage closure (LAAC) with NOAC therapy in non-valvular atrial fibrillation. LAAC significantly reduced non-procedural bleeding by 45–56% in moderate-risk patients, though this benefit attenuated in very high-risk, elderly cohorts. While successfully freeing eligible patients from lifelong anticoagulation, LAAC was associated with a consistent but statistically nonsignificant trend toward increased ischemic stroke. These clinical trade-offs establish LAAC as a highly effective, shared decision-making alternative to NOACs for carefully selected patients, emphasizing individualized risk profiling over universal device eligibility.