BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

Atrial Fibrillation NETwork Mendelstrasse 11 48149 Muenster Germany

Biomedical Research Foundation Academy of Athens Greece and Hygeia Hospitals Group Athens Greece

Biostatistics Lab School of Medicine University of Crete Crete Greece

Cardiac Department John Radcliffe Hospital Oxford University Hospitals NHS Foundation Trust Oxford UK

Cardiology Clinic St Anna University Hospital Medical University Sofia Sofia Bulgaria

Cardiology Department Fernando Fonseca Hospital Amadora Portugal

Cardiology Division European Georges Pompidou Hospital Paris France

Cardiovascular and Cell Sciences Research Institute St George's University of London and Imperial College London UK

Centre for Patient Reported Outcomes Research Institute of Applied Health Research University of Birmingham Edgbaston Birmingham UK

Centro de Investigacion Biomedica en Red Cardiovascular Madrid Spain

Danish Center for Health Services Research Department of Clinical Medicine Aalborg University Aalborg Denmark

Department of Cardiac Vascular Thoracic and Public Health Sciences Azienda Ospedaliera Padua Italy

Department of Cardiology and Intensive Care Medicine St Vincenz Hospital Paderborn Paderborn Germany

Department of Cardiology and Internal Diseases Medical University of Gdańsk Gdańsk Poland

Department of Cardiology Esbjerg Hospital University Hospital of Southern Denmark Esbjerg Denmark

Department of Cardiology Heraklion University Hospital Crete Greece

Department of Cardiology Institute for Clinical and Experimental Medicine Prague Czechia

Department of Cardiology School of Medical Sciences Faculty of Medicine and Health Örebro University Örebro Sweden

Department of Cardiology University Heart and Vascular Center Hamburg University Medical Center Hamburg Eppendorf Martinistrasse 52 Hamburg 20246 Germany

Department of Cardiology University Hospital Graz Graz Austria

Department of Internal Medicine 3 Cardiology and Angiology Innsbruck Medical University Innsbruck Austria

Department of Medical Science Uppsala University Uppsala Sweden

Department of Neuroepidemiology Institute for Medical Informatics Biometry and Epidemiology University Duisburg Essen Essen Germany

Department of Regional Health Research University of Southern Denmark Odense Denmark

Departments of Cardiology and Physiology Maastricht University Maastricht The Netherlands

German Center for Cardiovascular Research Partner Site Hamburg Kiel Luebeck Postdamer Str 58 10785 Berlin Germany

Heart and Vascular Centre Semmelweis University Budapest Hungary

Heart Center Department of Clinical and Experimental Cardiology Amsterdam Cardiovascular Sciences Amsterdam University Medical Centers University of Amsterdam Amsterdam The Netherlands

Hospital Clinic Universtitat de Barcelona Catalonia Barcelona Spain

HRMC University Hospital Brussels VUB Brussels Belgium

Institut d'Investigacions Biomèdiques August Pi Sunyer Catalonia Barcelona Spain

Institute of Medical Biometry and Epidemiology University Medical Centre Hamburg Eppendorf Hamburg Germany

Liverpool Centre for Cardiovascular Science at University of Liverpool Liverpool John Moores University and Liverpool Heart and Chest Hospital Liverpool UK

Medicine University 'Carol Davila' Colentina University Hospital Bucharest Romania

NIHR Birmingham Biomedical Research Centre and NIHR Applied Research Collaboration West Midlands University of Birmingham Edgbaston Birmingham UK

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$a Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24 h / $c N. Becher, T. Toennis, E. Bertaglia, C. Blomström-Lundqvist, A. Brandes, N. Cabanelas, M. Calvert, AJ. Camm, G. Chlouverakis, GA. Dan, W. Dichtl, HC. Diener, A. Fierenz, A. Goette, JR. de Groot, ANL. Hermans, GYH. Lip, A. Lubinski, E. Marijon, B. Merkely, L. Mont, AK. Ozga, K. Rajappan, A. Sarkozy, D. Scherr, RB. Schnabel, U. Schotten, S. Sehner, E. Simantirakis, P. Vardas, V. Velchev, D. Wichterle, A. Zapf, P. Kirchhof

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$a BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

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