Reduced-Dose NOACs or Aspirin Alone Comparable to DAPT After Left Atrial Appendage Closure: Study
Monotherapy with either reduced-dose non-vitamin K antagonist oral anticoagulants (NOACs) or aspirin alone was noninferior to dual antiplatelet therapy (DAPT) for 6-month clinical outcomes following uncomplicated left atrial appendage closure (LAAC). These findings suggest that simpler antithrombotic regimens may be viable alternatives to DAPT in selected patients. The study was published in JAMA by Vivek Y. and colleagues.
In assessing the effectiveness of de-escalated treatment regimens and their associated reduction in bleeding complications, researchers conducted an open-label, randomized clinical trial study involving 87 US-based investigational centers from October 2024 to December 2025, with final 6-month follow-ups made in July 2026. There were 1,857 patients with nonvalvular atrial fibrillation who underwent a successful LAAC procedure and eligible for the three types of antithrombotic treatments.
They were divided into groups 1:1:1. In Group 1, participants received DAPT for 6 months, followed by aspirin alone (n=624); Group 2 received NOAC at reduced dose for 3 months, followed by aspirin (n=620); and Group 3 received only aspirin for 12 months (n=613). The primary endpoint is the 6-month composite rate of all-cause mortality, stroke, systemic embolism, or major bleeding assessed through a 1-sided Farrington-Manning noninferiority test (alpha=0.025).
Key findings:
- Analysis among 1,857 enrolled trial participants (mean age, 76 ± 8 years; 42.9% women; mean CHA2DS2-VASc score, 4.2 ± 1.3; 68.0% paroxysmal AF) demonstrated noninferiority together with improved bleeding safety.
- The primary composite outcome was observed in 41 patients (6.9%) in the DAPT group, compared with 31 patients (5.1%) in the reduced-dose NOAC group (risk ratio, 0.75 [95% CI, 0.48–1.18]; risk difference, −1.7 percentage points; 97.5% upper bound, 1.2) and 20 patients (3.3%) in the aspirin monotherapy group (risk ratio, 0.49 [95% CI, 0.29–0.82]; risk difference, −3.5 percentage points; 97.5% upper bound, −0.8).
- Both de-escalation strategies were significantly noninferior to DAPT (both P < 0.001).
- Major bleeding was noted in 4.5% of the DAPT group, 2.7% of the reduced-dose NOAC group, and 1.7% of the aspirin monotherapy group.
- Clinically relevant nonmajor bleeding was observed in 8.7%, 4.8%, and 3.8% of participants, respectively.
- Exploratory 45-day transesophageal/CT imaging detected device-related thrombus in 3.4% of the DAPT group, 0.9% of the reduced-dose NOAC group, and 2.7% of the aspirin monotherapy group.
In summary, evidence from a multicenter randomized trial conducted for six months shows that both reduced-dose NOACs and aspirin monotherapy are non-inferior to standard DAPT after LAAC. The main conclusions from the study highlight the effectiveness of de-escalated medical management strategies in reducing bleeding risks without compromising stroke and device thrombosis rates.
Reference:
Reddy VY, Saliba WI, Waggoner T, et al. Antithrombotic Therapy After Left Atrial Appendage Occlusion: The SIMPLAAFY Randomized Clinical Trial. JAMA. Published online November 02, 2026. doi:10.1001/jama.2026.21361
