After left atrial appendage closure, aspirin alone or a low-dose anticoagulant was not worse than two antiplatelet drugs — SIMPLAAFY trial

Patients with atrial fibrillation who get a left atrial appendage closure (LAAC) device — an alternative to lifelong blood thinners — still need antithrombotic drugs for months afterwards. The SIMPLAAFY trial, published in JAMA on 2 November 2026, tested whether simpler regimens are good enough.

The study

• Design: open-label, three-arm randomised clinical trial at 87 US sites; 1,857 patients (mean age 76; 42.9% women) with nonvalvular atrial fibrillation after a successful, uncomplicated implant of the Watchman FLX Pro device.
• Arms: dual antiplatelet therapy (DAPT) for 6 months then aspirin; a reduced-dose NOAC (anticoagulant) for 3 months then aspirin; or aspirin alone.
• Primary outcome at 6 months (death, stroke, systemic embolism or major bleeding): 6.9% with DAPT, 5.1% with reduced-dose NOAC and 3.3% with aspirin alone. Both single-drug strategies met the prespecified non-inferiority criteria.

Bleeding and clots

Major bleeding was 4.5%, 2.7% and 1.7% respectively; clinically relevant non-major bleeding 8.7%, 4.8% and 3.8%. Device-related thrombus at 45 days was seen in 3.4%, 0.9% and 2.7%. Stroke rates were similar across groups.

Limitations

The trial was open-label; bleeding and thrombus results were exploratory without adjustment for multiple comparisons, and the trial was not powered to show differences in them, the accompanying editorial notes. Only patients with an uncomplicated implant who could take all three regimens were enrolled, follow-up for the primary outcome was 6 months, and there was no full-dose NOAC arm. The device maker’s website promotes the trial results. Patients should discuss their regimen with their cardiologist.