SIMPLAAFY Study: Less Intensive Antithrombotic Strategies Met Noninferiority Compared with DAPT After Left Atrial Appendage Closure
SAN DIEGO – New findings from the randomized SIMPLAAFY trial suggest that less intensive antithrombotic therapy following left atrial appendage closure (LAAC) with the WATCHMAN FLX™ Pro LAAC Device can reduce the risk of clinically-relevant bleeding without signs that such a strategy may compromise protection against thromboembolic events.
Findings were reported today at TCT® 2026, the annual scientific symposium of the Cardiovascular Research Foundation® (CRF®). TCT is the world’s premier educational meeting specializing in interventional cardiovascular medicine.
LAAC offers an alternative strategy to long-term oral anticoagulation (OAC) for reducing stroke risk in patients with atrial fibrillation. However, antithrombotic therapy following the procedure typically consists of short-term full-dose OAC or dual antiplatelet therapy (DAPT), which can increase risk of bleeding complications. This has led to growing interest in less intensive strategies, including reduced-dose OAC or aspirin monotherapy.
SIMPLAAFY was a multicenter, prospective, randomized controlled trial involving selected patients with nonvalvular atrial fibrillation undergoing LAAC who were deemed eligible for monotherapy strategies. After successful device implantation, 1,857 patients were randomized in a 1:1:1 ratio to one of three medication regimens: aspirin monotherapy for the trial duration (n=613), a reduced-dose non–vitamin K antagonist oral anticoagulant (NOAC) for three months followed by aspirin (n=620), or DAPT for six months followed by aspirin monotherapy (n=624).
The primary endpoint was the composite of all-cause death, stroke, systemic embolism or major bleeding at six months (aspirin alone: 3.3%, reduced-dose NOAC: 5.1%, DAPT: 6.9%). The absolute difference between aspirin and DAPT was 3.6% (p-value for noninferiority <0.0001), while the absolute difference between reduced NOAC and DAPT was 1.8% (p-value for noninferiority <0.0001), demonstrating noninferiority to DAPT for both monotherapies. Ischemic stroke rates were the same across all groups through six months (0.7%). Both monotherapy strategies were also associated with less clinically relevant bleeding than DAPT (8.7% for DAPT, 3.8% for aspirin alone and 4.8% for reduced-dose NOAC). Imaging at 45 days showed that device-related thrombus (DRT) appeared less frequently with reduced-dose NOAC (0.9%) compared with aspirin alone (2.7%) or DAPT (3.4%).
“These findings suggest that, after uncomplicated LAAC, antithrombotic therapy may be simplified to aspirin alone or a reduced-dose NOAC, with treatment tailored to each patient’s bleeding risk, risk of device-related thrombosis and personal preferences,” said Saibal Kar, MD, study co-chair, and program director, cardiovascular disease fellowship, Los Robles Health System, and National physician director, interventional cardiology, HCA healthcare, USA. “The prespecified 12-month analysis will also provide further insight into longer-term efficacy.”
The study was funded by Boston Scientific Corporation.
Dr. Kar disclosed consultant fees/honoraria from Abbott Vascular, Boston Scientific, InterShunt, Johnson and Johnson, Medtronic, Peija, V Wave, and W.L. Gore & Associates; and individual stock(s)/stock options from PiCardia.
The results of the study were presented on Monday, November 2 at 10:49 AM PT in the Main Arena at the San Diego Convention Center during TCT 2026.
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