Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation

Clinical Snapshot

Key Findings

• P Value: P = 0.44 for noninferiority

• Effect Size: Device group: 16.8 per 100 patient-years vs Medical therapy: 13.3 per 100 patient-years

• Primary Outcome: Composite of stroke, systemic embolism, major bleeding, or cardiovascular/unexplained death

• Nnt Or Sensitivity: Number needed to harm: approximately 29 patients (based on 3.5 excess events per 100 patient-years)

• Confidence Interval: Difference in restricted mean survival time: -0.36 years (95% CI: -0.70 to -0.01)

Clinical Application

LAA closure available in major Australian cardiac centres, requires specialised expertise and infrastructure Results challenge current practice where LAA closure considered for anticoagulation-ineligible patients. May influence TGA device approval considerations and private health insurance coverage decisions High-risk AF patients with CHA2DS2-VASc ≥4 and HAS-BLED ≥3, particularly elderly patients with contraindications to long-term anticoagulation

Abstract

BACKGROUND: Catheter-based closure of the left atrial appendage is an alternative to oral anticoagulation for stroke prevention in patients with atrial fibrillation. The effectiveness of this strategy, as compared with physician-directed best medical care, in patients at high risk for stroke and bleeding is unknown. METHODS: In this multicenter randomized trial conducted in Germany, we assigned patients with atrial fibrillation and a high risk of stroke and bleeding to undergo left atrial appendage closure or to receive physician-directed best medical care (including direct oral anticoagulants, if eligible). The primary end point, tested for noninferiority, was a composite of stroke (ischemic or hemorrhagic), systemic embolism, major bleeding, or cardiovascular or unexplained death, assessed in a time-to-event analysis. The noninferiority margin was a hazard ratio of 1.3. RESULTS: A total of 912 adult patients underwent randomization. The primary end-point analysis included 446 patients who were assigned to undergo left atrial appendage closure (device group) and 442 who were assigned to physician-directed best medical care (medical-therapy group). The mean (±SD) age was 77.9±7.1 years; 38.6% of the patients were women, the mean CHA2DS2-VASc score was 5.2±1.5 (range, 0 to 9, with higher scores indicating a greater risk of stroke), and the mean HAS-BLED score was 3.0±0.9 (range, 0 to 9, with higher scores indicating higher risk of bleeding). After a median follow-up of 3 years (interquartile range, 1.7 to 4.7), a first primary end-point event had occurred in 155 patients (incidence per 100 patient-years, 16.8) in the device group and in 127 patients (incidence per 100 patient-years, 13.3) in the medical-therapy group (difference in restricted mean survival time, -0.36 years; 95% confidence interval, -0.70 to -0.01; P = 0.44 for noninferiority). Serious adverse events occurred in 368 patients (82.5%) in the device group and 342 (77.4%) in the medical-therapy group. CONCLUSIONS: 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. (Funded by the German Center for Cardiovascular Research; CLOSURE-AF ClinicalTrials.gov number, NCT03463317.).

References

1. 1.Landmesser, U., Skurk, C., Kirchhof, P., Lewalter, T., Hartung, J., Rroku, A., Pieske, B., Brachmann, J., Akin, I., Jacobshagen, C., Meder, B., Zeiher, A., Anker, S. D., Thiele, H., Blankenberg, S., Massberg, S., Schunkert, H., Frey, N., Joost, A., Bergmann, M., von Bardeleben, R. S., Friede, T., Placzek, M., Suling, A., Haeusler, K. G., Endres, M., Wegscheider, K., Boldt, L.-H., & Eitel, I. (2026). Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation. *New England Journal of Medicine*. https://doi.org/10.1056/NEJMoa2513310