Key result
Percutaneous LAAC benefit over DOACs depends on patient phenotype, physiological reserve, and life expectancy.
Why the study?
Discordant evidence from CHAMPION-AF and CLOSURE-AF trials regarding percutaneous LAAC for stroke prevention in atrial fibrillation required reconciliation through a phenotype-based framework.
Does patient phenotype determine the net clinical benefit of percutaneous left atrial appendage closure compared to direct oral anticoagulation in patients with atrial fibrillation?
Does patient phenotype determine the net clinical benefit of percutaneous left atrial appendage closure compared to direct oral anticoagulation in patients with atrial fibrillation?
This review proposes a phenotype-based framework to reconcile discordant trial results, emphasizing that the long-term benefit of LAAC requires sufficient patient physiological reserve and life expectancy.
Supports phenotype-driven LAAC selection in AF; leaves open validation in stratified RCTs versus DOAC.
AIMS: The near-simultaneous publication of CHAMPION-AF and CLOSURE-AF produced apparently discordant evidence regarding percutaneous left atrial appendage closure (LAAC) for stroke prevention in atrial fibrillation. We aimed to reconcile these findings through a phenotype-based framework and identify the determinants of net clinical benefit. METHODS AND RESULTS: This narrative review integrates randomized trials, registries, consensus documents, and guidelines, focusing on patient selection, procedural risk, post-implant antithrombotic therapy, endpoint construction, competing mortality, and time to benefit. CHAMPION-AF evaluated LAAC against direct oral anticoagulation in an elective, anticoagulation-eligible population with lower bleeding risk, demonstrating non-inferior thromboembolic protection and less non-procedural bleeding. Conversely, CLOSURE-AF enrolled an older, multimorbid population with substantial renal dysfunction, previous bleeding, and high competing mortality. Although implantation success and stroke rates were comparable between treatment groups, early procedural and antithrombotic-related bleeding, a composite endpoint incorporating procedural events, and limited survival reduced the opportunity for delayed benefit. The highly selective recruitment pathway further limits generalisability. These findings define a continuum from the "CHAMPION-like" patient, with sufficient physiological reserve and life expectancy to realise long-term benefit, to the "CLOSURE-like" patient, in whom frailty and competing risk may outweigh the advantage of appendage exclusion. CONCLUSION: LAAC efficacy is not determined by device performance alone but by matching the intervention to patient phenotype and time horizon. Selection should integrate thromboembolic and bleeding risk, frailty, renal function, post-implant treatment tolerance, and expected survival. Future trials require transparent screening data, time-sensitive endpoints, landmark analyses, and competing-risk methods.
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Berti et al. (2026) conducted a review in Atrial fibrillation. Percutaneous left atrial appendage closure (LAAC) vs. Direct oral anticoagulation was evaluated. Percutaneous left atrial appendage closure efficacy for stroke prevention depends on matching the intervention to patient phenotype, physiological reserve, and life expectancy.
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