Antithrombotic Therapy After Left Atrial Appendage Occlusion
Vivek Y. Reddy, Walid I. Saliba, Thomas Waggoner, Devi G. Nair, Stanislav Weiner, Rudolph Evonich, Michael Hoskins, Andrew Dublin, Michael Rinaldi, Gaurang Gandhi, Jonathan W. Dukes, Madhu Reddy, David DeLurgio, Venkat R. Iyer, Ganesh Venkataraman, Ashish Sadhu, Vamsee Yaganti, Kevin Trulock, Douglas N. Gibson, Mohamad Alkhouli, Manish Shah, Shephal K. Doshi, Andrea Natale, Megan Coylewright, C. Michael Gibson, Ahmed A. Kolkailah, Wael A. Jaber, Krystal Leger, Elizabeth Matznick, Thomas Christen, Brad S. Sutton, Kenneth M. Stein, Saibal KarImportance
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: