Who can benefit from percutaneous left atrial appendage closure? Recent advances

Atrial fibrillation (AF) confers a substantial risk of stroke. Direct oral anticoagulants (DOACs) are highly effective for stroke prevention and form the cornerstone of AF management. Nevertheless, many eligible patients do not receive or do not maintain long-term anticoagulation because of bleeding risk, prior hemorrhage, or other contraindications. Percutaneous left atrial appendage closure (LAAC) has emerged as a non-pharmacological alternative. In 2026, two major randomized trials addressing the role of LAAC as an alternative to anticoagulation were published: CHAMPION-AF and CLOSURE-AF. CHAMPION-AF randomized 3000 lower-risk AF patients to LAAC (Watchman FLX) or DOAC. LAAC met noninferiority for the composite efficacy endpoint of cardiovascular death, stroke, and systemic embolism (5.7% vs 4.8% at 3 years; hazard ratio [HR] 1.20, 95% CI 0.87-1.66) and demonstrated superiority for non-procedure-related bleeding (10.9% vs 19.0%; HR 0.55). Ischemic stroke alone, however, was numerically more frequent with LAAC (HR 1.61), an unexpected finding not observed in prior LAAC trials. CLOSURE-AF enrolled a substantially higher-risk population with a more adverse bleeding profile. LAAC failed to demonstrate noninferiority to best medical therapy for the composite primary endpoint consisting of cardiovascular death, stroke, systemic embolism, and major bleeding (16.8 vs 13.3 events per 100 patient-years), driven by higher mortality and more bleeding events in the device group. This review critically appraises the design, outcomes, and clinical implications of both trials in the context of previous trials, discusses methodological issues including noninferiority margin selection and bleeding-endpoint definitions, and outlines implications for patient selection for LAAC.