CHAMPION-AF: Left Atrial Appendage Closure Noninferior to NOACs

Device-based left atrial appendage closure (LAAC) was noninferior to non-vitamin K antagonist oral anticoagulant (NOAC) therapy for prevention of adverse events in patients with atrial fibrillation (AF) who were eligible candidates for long-term anticoagulation, according to results of the CHAMPION-AF trial published in the New England Journal of Medicine and simultaneously presented at the American College of Cardiology's Annual Scientific Session (ACC.26) in New Orleans.1

“Although non-vitamin K antagonist oral anticoagulants, also called NOACs, are currently the preferred treatment approach for reducing stroke risk in these patients, their effectiveness may be limited by risks associated with bleeding and medication non-adherence,” said coprincipal investigator Saibal Kar, MD, program director of the cardiovascular disease fellowship at Los Robles Regional Medical Center in California and national physician director of Interventional Cardiology at HCA Healthcare USA.2

CHAMPION-AF Trial Design

Funded by Boston Scientific, CHAMPION-AF was a prospective, international, randomized trial enrolling 3000 patients with non-valvular AF at elevated stroke risk across 141 sites in 16 countries. The study cohort had a mean patient age of 71.7 (SD, 7.5) years, 31.9% were women, a mean CHA₂DS₂-VASc score of 3.5 (SD, 1.3), and a mean HAS-BLED score of 1.3 (SD, 0.8). Investigators noted 47.8% had undergone prior AF ablation.1

Patients were randomized 1:1 to receive the Watchman Flx device, which received FDA approval in July 2020, or an approved NOAC. Following device implantation, patients in the LAAC group received short-term antithrombotic therapy for 3 months before transitioning to antiplatelet monotherapy. The primary efficacy endpoint was a composite of cardiovascular death, stroke, or systemic embolism, tested for noninferiority (margin, 4.8 percentage points) at 3 years. The primary safety endpoint was non-procedure-related bleeding, tested for superiority.1,3

CHAMPION-AF Efficacy and Safety Outcomes

At 3 years, the primary efficacy endpoint occurred in 81 patients (Kaplan-Meier estimate, 5.7%) in the device group and 65 patients (4.8%) in the NOAC group, which yielded a difference of 0.9 percentage points (95% CI, -0.8 to 2.6; P <.001 for noninferiority). Additionally, Cardiovascular mortality was similar between groups (2.7% in each). Ischemic stroke occurred in 3.2% of device group patients versus 2.2% of NOAC patients, with follow-up through 5 years planned to further assess this difference.1

Non-procedure-related bleeding, the primary safety endpoint, occurred in 10.9% of device group patients versus 19.0% of NOAC patients (HR, 0.55; 95% CI, 0.45 to 0.67; P <.001 for superiority), which investigators pointed out represents a nearly 45% relative risk reduction in bleeding. This advantage was driven primarily by clinically relevant nonmajor bleeding (7.0% vs 14.2%), while ISTH major bleeding alone was not significantly different between groups (5.1% vs 6.4%). The net clinical benefit composite of cardiovascular death, stroke, systemic embolism, or non-procedure-related bleeding favored LAAC over NOAC therapy (15.1% vs 21.8%; P <.001 for noninferiority).1

Within 30 days of the procedure, pericardial effusions requiring intervention occurred in 0.7% of device group patients. Device-related thrombus was detected in 4.8% of patients assessed at 4 months, with 1.8% meeting criteria for clinically relevant thrombus requiring resumption of anticoagulation. The investigators highlighted increased use of CT angiography during the COVID-19 pandemic may have elevated detection of subtle changes not representing true clinically significant thrombus.1

"Our data suggest that the left atrial appendage closure device used in this trial is a potential and reasonable alternative to medication, even among patients who are suitable for long-term blood thinners, and may be discussed as part of a shared decision-making process," Kar added.

Clinical Context and Limitations

According to investigators, CHAMPION-AF sought to address a meaningful evidence gap. Prior randomized data supporting LAAC, such as the PREVAIL and PROTECT AF trials, were conducted in patients unsuitable for long-term anticoagulation. This trial is the first to prospectively compare LAAC against DOACs in a population deemed appropriate for either treatment strategy, regardless of prior ablation status.1

The authors identified several limitations. The noninferiority margin was defined on an absolute rather than relative scale, and the observed event rate was lower than anticipated, which has implications for how the margin is interpreted in relative terms. Results are specific to the Watchman Flx device and the post-implant antithrombotic regimen used in this trial and should not be extrapolated to other devices or protocols. Patients with CHA₂DS₂-VASc scores of 5 or higher were underrepresented, which limits generalizability to the highest-risk AF population.1,2

References:

1. Doshi SK, Kar S, Nair DG. Left Atrial Appendage Closure or Anticoagulation for Atrial Fibrillation. New England Journal of Medicine. Published online March 28, 2026. Accessed March 28, 2026. doi: 10.1056/NEJMoa2517213

2. American College of Cardiology. Left Atrial Appendage Closure Noninferior to Blood Thinners for Lowering Stroke Risk, Death in Some Patients with AFib . ACC Media Center. Published March 28, 2026. Accessed March 28, 2026. https://www.acc.org/about-acc/press-releases

3. Boston Scientific. Boston Scientific Announces FDA Approval for the Latest-Generation WATCHMAN FLXTM Pro Left Atrial Appendage Closure Device. Boston Scientific. Published September 6, 2023. Accessed March 28, 2026. https://news.bostonscientific.com/2023-09-06-Boston-Scientific-Announces-FDA-Approval-for-the-Latest-Generation-WATCHMAN-FLX-TM-Pro-Left-Atrial-Appendage-Closure-Device