Reduced Dose-Direct Oral Anticoagulant Vs Dual Antiplatelet Therapy After Left Atrial Appendage Closure in Patients With Nonvalvular Atrial Fibrillation: A Systematic Review and Meta Analysis

Abstract

Background:

Reduced-dose direct oral anticoagulants (DOACs) are increasingly used after left atrial appendage closure (LAAC) in nonvalvular atrial fibrillation (NVAF), but their benefit over dual antiplatelet therapy (DAPT) remains uncertain.

Objective:

To evaluate the efficacy, safety, and net clinical benefit of reduced-dose DOAC versus DAPT following percutaneous LAAC in adults with NVAF.

Methods:

A systematic review and meta-analysis of randomized controlled trials and observational cohorts comparing reduced-dose DOAC (apixaban 2.5 mg twice daily or rivaroxaban 10-15 mg once daily) with DAPT after successful LAAC in adults (≥18 years) with NVAF was conducted by searching PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov from inception through February 2026. Dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using random-effects models; heterogeneity was assessed with I² and χ² statistics. Analyses were performed with RevMan 5.4.

Results:

Seven studies (3 randomized controlled trials, 4 cohorts) including 2126 patients (reduced-dose DOAC = 1088; DAPT = 1038) were analyzed. Reduced-dose DOAC significantly reduced composite thromboembolic events (RR = 0.20, 95% CI = 0.10-0.39; I² = 0%), ischemic stroke (RR = 0.33, 95% CI = 0.13-0.80; I² = 0%), and device-related thrombosis (RR = 0.33, 95% CI = 0.18-0.60; I² = 0%) compared with DAPT. The net clinical benefit composite (thromboembolism plus major bleeding) favored reduced-dose DOAC (RR = 0.36, 95% CI = 0.19-0.70; I² = 63%), with apixaban-predominant subgroups showing strongest effects (RR = 0.14, 95% CI = 0.05-0.36). Major bleeding was lower (RR = 0.54, 95% CI = 0.35-0.83; I² = 0%), any bleeding reduced (RR = 0.52, 95% CI = 0.30-0.88; I² = 64%), and minor bleeding trended lower (RR = 0.66, 95% CI = 0.42-1.02; I² = 34%), whereas cardiovascular (RR = 0.66, 95% CI = 0.23-1.92) and all-cause mortality (RR = 0.74, 95% CI = 0.42-1.30) did not differ significantly between groups.

Conclusion and Relevance:

Reduced-dose DOAC therapy after LAAC lowered thromboembolic events, device-related thrombosis, and major bleeding versus DAPT, without affecting mortality. These findings support consideration of reduced-dose DOACs, especially apixaban-based regimens, in appropriately selected patients.