Design: Open-label, three-arm, multicentre randomised non-inferiority trial (SIMPLAAFY)
Population: 1857 US patients with non-valvular AF after successful left atrial appendage occlusion
Primary outcome: Death, stroke, systemic embolism or major bleeding at 6 months
Effect: 6.9% DAPT vs 5.1% reduced-dose anticoagulant vs 3.3% aspirin; aspirin RR 0.49 (0.29 to 0.82)

SIMPLAAFY was an open-label, three-arm randomised trial at 87 US sites. It enrolled 1857 patients with non-valvular atrial fibrillation (mean age 76, mean CHA2DS2-VASc 4.2) after successful left atrial appendage occlusion. They received six months of dual antiplatelet therapy then aspirin, three months of reduced-dose oral anticoagulant then aspirin, or aspirin alone for 12 months.

The six-month composite of death, stroke, systemic embolism or major bleeding was 6.9% with dual antiplatelets, 5.1% with reduced-dose anticoagulant (risk ratio 0.75, 95% CI 0.48 to 1.18) and 3.3% with aspirin alone (0.49, 0.29 to 0.82). Both simpler regimens met non-inferiority. Major bleeding was 4.5%, 2.7% and 1.7%. Device-related thrombus at 45 days was 3.4%, 0.9% and 2.7%, an exploratory result.

Many of these patients have occlusion precisely because they bled on anticoagulants, so stacking two antiplatelets afterwards has always been uncomfortable. This trial supports a simpler start. Patients were selected as eligible for all three regimens and the procedure was uncomplicated, so device-specific and operator guidance still applies, and a patient with a known thrombus or leak is outside this evidence.

Discuss aspirin monotherapy with the implanting team after uncomplicated appendage occlusion.
Reserve dual antiplatelet therapy for a specific reason rather than as the default.
Consider short reduced-dose anticoagulation where thrombus risk worries you; it had the lowest thrombus rate.
Make sure the follow-up imaging for device thrombus still happens.
Follow the device manufacturer's labelled regimen until local protocols change.

Why it matters

The patients who need appendage occlusion are the ones who bleed, and the default after it has been the most bleeding-prone choice.

The statistics, in plain English

Non-inferiority means the simpler regimen was shown not to be meaningfully worse, within a margin set in advance. The aspirin arm's composite was actually lower, mainly through less bleeding. Bleeding and thrombus results were exploratory and not adjusted for multiple testing, so treat them as supportive. Six months is short for late device thrombus.