For patients with atrial fibrillation (AF) at high risk for both stroke and bleeding, catheter-based left atrial appendage closure (LAAC) was not found to be non-inferior to physician-directed best medical care, according to the results of the CLOSURE-AF trial.¹
Methodology
The multicentre, randomised CLOSURE-AF trial was conducted in Germany to assess the effectiveness of LAAC compared with best medical care in this high-risk patient population. The trial enrolled 912 adult patients with AF who were at high risk of stroke and bleeding. Patients were assigned to either undergo LAAC (device group, n=446) or receive physician-directed best medical care (medical-therapy group, n=442), which could include direct oral anticoagulants if the patient was eligible.
The patient cohort had a mean age of 77.9 years, and 38.6% were women. The mean CHA₂DS₂-VASc score was 5.2, indicating a high risk of stroke, and the mean HAS-BLED score was 3.0, indicating a high risk of bleeding.
The primary endpoint was a composite of stroke (ischaemic or haemorrhagic), systemic embolism, major bleeding, or cardiovascular or unexplained death. The study was designed as a non-inferiority trial, with a pre-specified non-inferiority margin of a hazard ratio of 1.3.
Results
After a median follow-up of 3 years, a first primary endpoint event had occurred in 155 patients in the device group, corresponding to an incidence of 16.8 per 100 patient-years. In the medical-therapy group, 127 patients experienced a primary endpoint event, with an incidence of 13.3 per 100 patient-years.
The analysis did not meet the criterion for non-inferiority (difference in restricted mean survival time, −0.36 years; 95% confidence interval, −0.70 to −0.01; P=0.44 for non-inferiority). Serious adverse events were reported in 82.5% of patients in the device group and 77.4% in the medical-therapy group.
In Practice
The findings suggest that for this specific patient group, LAAC does not offer a non-inferior alternative to best medical care for the composite outcome studied. The CLOSURE-AF Trial Investigators concluded, "Among patients with atrial fibrillation at high risk for stroke and bleeding, left atrial appendage closure was not noninferior to physician-directed best medical care with regard to a composite end point of stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death."¹ This outcome has been described in an accompanying editorial as highlighting a potential overuse of the method in cardiology.²
This study was funded by the German Center for Cardiovascular Research.
References
1. Landmesser U, Skurk C, Kirchhof P, et al. Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation. N Engl J Med. 2026. https://doi.org/10.1056/NEJMoa2513310
2. Widimský P. Left Atrial Appendage Closure — Another Overused Method in Cardiology? N Engl J Med. 2026. https://doi.org/10.1056/NEJMe2518067
Disclaimer
The information presented in this article is for educational purposes only. Any quotes included reflect the opinions of the individual quoted, and do not necessarily reflect the views of the publisher. The publisher does not guarantee the accuracy or completeness of the content and accepts no responsibility for any errors, or any consequences arising from its use.