Antithrombotic Therapy After Left Atrial Appendage Occlusion

Abstract

Importance Following a left atrial appendage closure (LAAC) procedure, antithrombotic therapy is administered to safely allow time for device endothelialization. However, the optimal postimplant antithrombotic regimen is unknown. Objective To determine if either reduced-dose non–vitamin K oral anticoagulants (NOACs) or aspirin alone are noninferior to dual antiplatelet therapy (DAPT) for the composite clinical end point of death, stroke, systemic embolism, or major bleeding through 6 months post LAAC. Design, Setting, and Participants This open-label, 3-group, multicenter clinical trial randomized 1857 patients between October 2024 and December 2025 at 87 US investigational sites, with the final 6-month follow-up in July 2026. Enrolled patients had nonvalvular atrial fibrillation, underwent successful LAAC, and were eligible for all 3 regimens. Interventions Patients were randomly allocated 1:1:1 to DAPT for 6 months followed by aspirin (n = 624), a reduced-dose NOAC for 3 months followed by aspirin (n = 620), or aspirin alone for 12 months (n = 613). Main Outcomes and Measures The primary outcome was the 6-month composite of all-cause death, stroke, systemic embolism, or major bleeding. Noninferiority was tested in the primary analysis population with a 1-sided Farrington-Manning test (α = .025). Bleeding and 45-day device-related thrombus rates were exploratory without multiplicity adjustment. Results The cohort had a mean age of 76 (SD, 8) years, 42.9% were female, the mean CHA 2 DS 2 -VASc score was 4.2 (SD, 1.3), and 68.0% had paroxysmal atrial fibrillation. The primary outcome occurred in 41 patients (6.9%) with DAPT vs 31 (5.1%) with a reduced-dose NOAC (risk ratio, 0.75 [95% CI, 0.48-1.18]; risk difference, −1.7 percentage points; 97.5% upper bound, 1.2) and 20 (3.3%) with aspirin alone (risk ratio, 0.49 [95% CI, 0.29-0.82]; risk difference, −3.5 percentage points; 97.5% upper bound, −0.8). Both monotherapy strategies met noninferiority criteria ( P < .001 for noninferiority for both). Major bleeding was 4.5% with DAPT, 2.7% with reduced-dose NOACs, and 1.7% with aspirin alone; clinically relevant nonmajor bleeding was 8.7%, 4.8%, and 3.8%, respectively. Device-related thrombus was observed in 3.4%, 0.9%, and 2.7%, respectively. Conclusions and Relevance Both reduced-dose NOACs and aspirin alone were noninferior to DAPT for 6-month outcomes after uncomplicated LAAC. Trial Registration ClinicalTrials.gov Identifier: NCT06521463