Reduced-dose direct oral anticoagulant versus antiplatelet strategies after left atrial appendage occlusion

The optimal antithrombotic therapy after left atrial appendage occlusion (LAAO) in patients with atrial fibrillation (AF) remains uncertain. Reduced-dose direct oral anticoagulation (DOAC) is increasingly used in clinical practice as an alternative to antiplatelet-based strategies, but comparative outcome data are limited.

We sought to compare the clinical outcomes associated with low-dose DOAC therapy versus dual antiplatelet therapy (DAPT) or single antiplatelet therapy (SAPT) after LAAO.

Using the TriNetX Global Network, we identified adult patients with AF who underwent percutaneous LAAO between 2010 and 2025. Three parallel propensity score-matched analyses were conducted: reduced-dose DOAC versus DAPT, SAPT versus DAPT, and reduced-dose DOAC versus SAPT. Outcomes included all-cause death, thromboembolic events, device-related thrombosis, bleeding events, and net clinical benefit (NCB).

After matching, 1,773 patients were included in each group for the reduced-dose DOAC versus DAPT comparison (mean follow-up 1.4±1.0 years). Reduced-dose DOAC was associated with lower risks of all-cause death (hazard ratio [HR] 0.79, 95% confidence interval [CI]: 0.65-0.96) and major bleeding (HR 0.87, 95% CI: 0.77-0.98), with no significant differences in ischaemic stroke, thromboembolism, or device-related thrombosis. NCB favoured reduced-dose DOAC (HR 0.87, 95% CI: 0.78-0.96). SAPT was also associated with fewer bleeding events and favourable outcomes compared with DAPT. In the reduced-dose DOAC versus SAPT comparison (1,582 matched patients per group), reduced-dose DOAC showed estimates compatible with a slightly higher risk of major bleeding compared with SAPT (HR 1.14, 95% CI: 1.00-1.30; p=0.06), while mortality, thromboembolic outcomes, and NCB did not differ significantly.

In contemporary practice after LAAO, reduced-dose DOAC therapy was associated with more favourable outcomes than DAPT but showed no clear advantage over SAPT, supporting simplified and individualised post-implantation antithrombotic strategies.