24 Jun 2026
LAA closure: Will CHAMPION-AF change guidelines and clinical practice?
CHAMPION-AF trial in perspective
Tom De Potter explores the evolving role of left atrial appendage closure (LAAC), highlighting how recent evidence is reshaping stroke prevention strategies and expanding its place in the management of atrial fibrillation.
Atrial fibrillation and stroke prevention: current standards
Atrial fibrillation (AF) is the most common sustained arrhythmia and has an associated risk of ischemic stroke which can be substantial depending on patient profile. The standard of care for primary and secondary prevention of stroke is oral anticoagulation using direct-acting oral anticoagulants (DOAC), which has well-known safety and efficacy as well as documented challenges such as bleeding risk or compliance issues.
Percutaneous left atrial appendage closure (LAAC) was developed to address some of these issues and has historically been reserved for those patients deemed unsuitable for long-term anticoagulation therapy, and even in this population, its application is not without debate. CHAMPION-AF is the first trial to investigate whether LAAC can move from a fallback option to a first-line choice in stroke prophylaxis for AF patients, and the largest randomized trial in the LAAC space overall thus far.
CHAMPION-AF: a landmark trial in LAAC
CHAMPION-AF randomized 3000 patients indicated and suitable for anticoagulation therapy to either LAAC or DOAC treatment, and recently reported its 3-year follow-up data on safety and efficacy endpoints (the study is designed to follow patients for 5 years in total). At the 3y follow-up point, the trial met its primary efficacy endpoint, demonstrating statistical non-inferiority for a composite of cardiovascular death, stroke and systemic embolism (5.7% for LAAC vs 4.8% for DOAC, p <0.001 for noninferiority); and showed superiority for the endpoint of non-procedural bleeding (10.9% for LAAC vs 19.0% for DOAC, p<0.001 for superiority) (ref PMID 41910347). These data make CHAMPION-AF the first large, DOAC-era RCT to deliver a formally positive result for a device strategy in a broad population.
Interpreting the results: efficacy and safety
Publication of CHAMPION-AF has sparked debate on whether bleeding rates in the primary endpoint are relevant enough given procedural bleedings were excluded, and on a numerically higher (non-significant) stroke rate in the device arm. While discussions on methodology and trial orthodoxy appropriately highlight which questions the trial can and can not answer, the more relevant question to the practitioner is much more straightforward: will this data change clinical practice? The bleeding benefit for patients is convincingly demonstrated in secondary analyses, including all bleeding types, maintaining a clearly favourable outcome for WATCHMAN FLX (12.8 vs 19.0% events, p < 0.001) and is a very relevant issue for many patients on anticoagulation or in whom anticoagulation is considered. This leaves the question of efficacy (i.e. stroke prevention), where indeed a numerical difference is observed. It is worth noting the annualized ischemic stroke rate observed with WATCHMAN FLX was 1.1%, perfectly aligned with the historical stroke rates of the original pivotal trials establishing NOAC safety and efficacy. Additionally, the primary efficacy endpoint at the current 3-year follow-up interval is prespecified to combine cardiovascular death, stroke and systemic embolism. CHAMPION-AF trial is designed to specifically report on the incidence of ischemic stroke and systemic embolism in isolation at 5-year follow-up as a primary endpoint, and thus will be able to provide evidence on this topic in 2 years.
Data from the recent CLOSURE-AF trial demonstrated LAAC failing to match medical therapy in highly frail, high-bleeding risk patients, emphasizing that LAAC is highly sensitive to patient selection. The CHAMPION-AF cohort is arguably an almost opposite population of younger patients, suitable for NOAC therapy but also at low risk for procedural complications and eligible to benefit from long time horizon benefits in terms of bleeding reduction.
Implications for clinical practice and decision-making
Physicians are therefore provided with a new body of evidence enabling evidence-based shared decision making, offering patients a valid choice between comprehensive but adherence-dependent systemic protection of NOACs and localized, low-bleeding profile protection of LAAC for those patients with a profile comparable to the CHAMPION-AF population. The negative CLOSURE-AF trial reinforces the risk of overgeneralizing this treatment option to an elderly, high-risk population.
CHAMPION-AF 5-year follow-up data on thromboembolic events will be essential to further strengthen or weaken support for LAAC as a more general approach to stroke prevention in an all-comer population.
