TY - JOUR
T1 - Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes
AU - NOAH-AFNET 6 Investigators
AU - Kirchhof, Paulus
AU - Toennis, Tobias
AU - Goette, Andreas
AU - Camm, A. John
AU - Diener, Hans Christoph
AU - Becher, Nina
AU - Bertaglia, Emanuele
AU - Blomstrom Lundqvist, Carina
AU - Borlich, Martin
AU - Brandes, Axel
AU - Cabanelas, Nuno
AU - Calvert, Melanie
AU - Chlouverakis, Gregory
AU - Dan, Gheorghe-Andrei
AU - de Groot, Joris R.
AU - Dichtl, Wolfgang
AU - Kravchuk, Borys
AU - Lubiński, Andrzej
AU - Marijon, Eloi
AU - Merkely, B. la
AU - Mont, Lluís
AU - Ozga, Ann-Kathrin
AU - Rajappan, Kim
AU - Sarkozy, Andrea
AU - Scherr, Daniel
AU - Sznajder, Rafał
AU - Velchev, Vasil
AU - Wichterle, Dan
AU - Sehner, Susanne
AU - Simantirakis, Emmanuel
AU - Lip, Gregory Y. H.
AU - Vardas, Panos
AU - Schotten, Ulrich
AU - Zapf, Antonia
N1 - Funding Information: This investigator-initiated, double-blind, double-dummy, randomized trial was conducted in 18 European countries. Details of the trial design have been described previously. The , including the statistical analysis plan, is available with the full text of this article at NEJM.org. The protocol was approved by the institutional review boards at each participating site. All the patients provided written informed consent before enrollment. The trial was designed and overseen by a steering committee. During the trial, the steering committee was supported by a national coordinators committee. The trial was conducted in accordance with the principles of the Declaration of Helsinki and with the Good Clinical Practice guidelines of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Details regarding the participating sites and committee members are provided in the , available at NEJM.org. An independent data and safety monitoring board guided the trial. All reports of serious adverse events were adjudicated by an independent outcome review committee whose members were unaware of the trial-group assignments. Publisher Copyright: © 2023 Massachusetts Medical Society.
PY - 2023/9/28
Y1 - 2023/9/28
N2 - BACKGROUND: Device-detected atrial high-rate episodes (AHREs) are atrial arrhythmias detected by implanted cardiac devices. AHREs resemble atrial fibrillation but are rare and brief. Whether the occurrence of AHREs in patients without atrial fibrillation (as documented on a conventional electrocardiogram [ECG]) justifies the initiation of anticoagulants is not known. METHODS: We conducted an event-driven, double-blind, double-dummy, randomized trial involving patients 65 years of age or older who had AHREs lasting for at least 6 minutes and who had at least one additional risk factor for stroke. Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding. RESULTS: The analysis population consisted of 2536 patients (1270 in the edoxaban group and 1266 in the placebo group). The mean age was 78 years, 37.4% were women, and the median duration of AHREs was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed. A primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.60 to 1.08; P = 0.15). The incidence of stroke was approximately 1% per patient-year in both groups. A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (hazard ratio, 1.31; 95% CI, 1.02 to 1.67; P = 0.03). ECG-diagnosed atrial fibrillation developed in 462 of 2536 patients (18.2% total, 8.7% per patient-year). CONCLUSIONS: Among patients with AHREs detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite of cardiovascular death, stroke, or systemic embolism as compared with placebo, but it led to a higher incidence of a composite of death or major bleeding. The incidence of stroke was low in both groups. (Funded by the German Center for Cardiovascular Research and others; NOAH-AFNET 6 ClinicalTrials.gov number, NCT02618577; ISRCTN number, ISRCTN17309850.).
AB - BACKGROUND: Device-detected atrial high-rate episodes (AHREs) are atrial arrhythmias detected by implanted cardiac devices. AHREs resemble atrial fibrillation but are rare and brief. Whether the occurrence of AHREs in patients without atrial fibrillation (as documented on a conventional electrocardiogram [ECG]) justifies the initiation of anticoagulants is not known. METHODS: We conducted an event-driven, double-blind, double-dummy, randomized trial involving patients 65 years of age or older who had AHREs lasting for at least 6 minutes and who had at least one additional risk factor for stroke. Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding. RESULTS: The analysis population consisted of 2536 patients (1270 in the edoxaban group and 1266 in the placebo group). The mean age was 78 years, 37.4% were women, and the median duration of AHREs was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed. A primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.60 to 1.08; P = 0.15). The incidence of stroke was approximately 1% per patient-year in both groups. A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (hazard ratio, 1.31; 95% CI, 1.02 to 1.67; P = 0.03). ECG-diagnosed atrial fibrillation developed in 462 of 2536 patients (18.2% total, 8.7% per patient-year). CONCLUSIONS: Among patients with AHREs detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite of cardiovascular death, stroke, or systemic embolism as compared with placebo, but it led to a higher incidence of a composite of death or major bleeding. The incidence of stroke was low in both groups. (Funded by the German Center for Cardiovascular Research and others; NOAH-AFNET 6 ClinicalTrials.gov number, NCT02618577; ISRCTN number, ISRCTN17309850.).
KW - Arrhythmias/Pacemakers/Defibrillators
KW - Cardiology
KW - Hematology/Oncology
KW - Hematology/Oncology General
KW - Neurology/Neurosurgery
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=85172284519&partnerID=8YFLogxK
U2 - https://doi.org/10.1056/NEJMoa2303062
DO - https://doi.org/10.1056/NEJMoa2303062
M3 - Article
C2 - 37622677
SN - 0028-4793
VL - 389
SP - 1167
EP - 1179
JO - The New England journal of medicine
JF - The New England journal of medicine
IS - 13
ER -