Key result
LAAC fails to show noninferiority to best medical care for major events.
Why the study?
Does left atrial appendage closure improve outcomes compared to physician-directed best medical care in patients with atrial fibrillation at high risk for stroke and bleeding?
RCT
Does left atrial appendage closure improve outcomes compared to physician-directed best medical care in patients with atrial fibrillation at high risk for stroke and bleeding?
In high-risk patients with atrial fibrillation, left atrial appendage closure failed to demonstrate noninferiority to best medical care for preventing stroke, bleeding, and death.
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Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Patients at high risk are probably not optimal candidates for this procedure.”
“The composite endpoint included both embolic events and bleeding, but both types of events were more common in the LAAC arm to a degree that the prespecified margin of noninferiority was missed.”
“Yet, he acknowledged that the results were surprising and disappointing because this is the population in which LAAC is most often used in his center.”
Reinforces medical therapy as standard in high-risk AF; challenges positive prior LAAO trials and guidelines.
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.).
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Landmesser et al. (2026) conducted an RCT in Atrial fibrillation. Left atrial appendage closure vs. Physician-directed best medical care was evaluated on Composite of stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death. Left atrial appendage closure was not noninferior to physician-directed best medical care for a composite of stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death.
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