IMPORTANCE: In the Left Atrial Appendage Occlusion Study III (LAAOS III), surgical occlusion of the LAA during cardiac surgery for patients with known history of atrial fibrillation (AF) substantially reduced the risk of stroke. OBJECTIVE: To assess the impact of LAAO on ischemic stroke subtype and outcome. DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc exploratory analysis of the LAAOS III randomized clinical trial. Data were adjudicated from June 28, 2023, to November 29, 2023, and the main analyses took place from December 18, 2023, to April 29, 2024. The LAAOS III trial recruited participants from 105 centers in 27 countries between July 2012 and October 2018. Patients with AF and a CHA2DS2-VASc score of at least 2 undergoing cardiac surgery for other indications were included in the analysis. INTERVENTIONS: Surgical LAAO plus standard care vs standard care alone. MAIN OUTCOMES AND MEASURES: For strokes occurring during the trial, the functional outcome as measured by the modified Rankin Scale (mRS) score at day 7 or discharge, mortality, the presence of cortical infarcts, and the occurrence of infarcts of presumed cardioembolic origin were examined. RESULTS: Of 4811 participants in the LAAOS III trial followed up for 3.8 years, 273 had a first ischemic stroke. The mean (SD) age of participants at the time of the first ischemic stroke was 75 (7) years, 104 were female (38%), and 169 were male (62%). Participants allocated to receive LAAO had reduced (common odds ratio [OR], 0.80; 95% CI, 0.65-0.99) mRS scores at 7 days or discharge and a lower risk for mortality at 30 days (16.5% vs 20.1%; hazard ratio [HR], 0.55; 95% CI, 0.31-0.97) after a stroke event. Participants allocated to LAAO had fewer cortical infarcts on neuroimaging (46.2% vs 61.3%; difference in proportions: -15.2%; 95% CI, -26.7% to -3.7%), as well as a lower proportion of ischemic strokes of presumed cardioembolic etiology when compared with ischemic strokes in the no-LAAO group (42.9% vs 57.9%; difference in proportions: -15.1%; 95% CI, -26.5% to -3.7%). CONCLUSIONS AND RELEVANCE: This study found that LAAO in patients with AF undergoing cardiac surgery was associated with a decreased risk of presumed cardioembolic stroke, reduced disability, and mortality from stroke. These findings underscore the benefit of LAAO for patients with AF undergoing cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01561651.

1st Department of Neurology Medical School Faculty of Health Sciences Aristotle University of Thessaloniki Macedonia Greece

Department of Neurology Centro Hospitalar Lisboa Ocidental Lisbon Portugal

Department of Neurology Cliniques Universitaires Saint Luc UCLouvain Brussels Belgium

Department of Neurology Jagiellonian University Medical College Krakow Poland

Department of Neurology Military University Hospital Prague Prague Czech Republic

Department of Neurology St Anne's University Hospital Masaryk University Brno Czech Republic and Department of Neurology Tomas Bata Hospital Zlin Czech Republic

Division of Cardiac Surgery Department of Surgery McMaster University Hamilton Ontario Canada

Division of Neurology Department of Medicine McMaster University Hamilton Ontario Canada

Divisions of Cardiology and Critical Care Department of Medicine McMaster University Hamilton Ontario Canada

Neurovascular Treatment Unit Spaziani Hospital Frosinone Italy

Population Health Research Institute and Hamilton Health Sciences Hamilton Ontario Canada

Université de Montréal Faculté de Médecine Département de Neurosciences Montréal Québec Canada

University of Ostrava Faculty of Medicine Department of Clinical Neurosciences Ostrava Czech Republic

Wolfson Centre for Prevention of Stroke and Dementia Nuffield Department of Clinical Neurosciences Oxford University United Kingdom

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