Anticoagulants prevent strokes in patients with atrial fibrillation but are not effective in those without atrial fibrillation, for example in patients with heart failure. Atrial high-rate episodes (AHRE) are short and rare atrial arrhythmias that resemble atrial fibrillation detected by implanted pacemakers, defibrillators, and loop recorders. AHRE are found in 10-30% of patients with implanted devices [1]. While AHRE are associated with an increased risk of stroke, the risk is lower than for those with atrial fibrillation. ESC guidelines recommend oral anticoagulation to prevent stroke in patients with atrial fibrillation and increased stroke risk and propose individualised decisions in patients with AHRE, but without ECG-documented atrial fibrillation [2].
NOAH-AFNET 6 was the first randomised, double-blind, double-dummy trial to investigate the efficacy and safety of oral anticoagulation in patients with AHRE, but without ECG-documented atrial fibrillation.4
NOAH-AFNET 6 was presented at ESC Congress 2023 and simultaneously published in the New England Journal of Medicine.
The primary, modified intention-to-treat analysis population consisted of 2,536 patients who received at least one dose of study drug. Patients were elderly with multiple stroke risk factors: the mean age was 78 years, 37% were women and the median CHA2DS2-VASc score was 4.5 The median AHRE duration at baseline was 2.8 hours without an upper limit, and 97% of AHRE showed atrial rates >200 beats per minute, clearly resembling atrial fibrillation.
The trial was stopped early due to safety signals and a trend towards futility for efficacy after enrolment of all planned patients. The stroke rate was low in both randomised groups (without anticoagulation 1.1%/year, with anticoagulation 0.9%/year). The difference in safety outcomes was driven by an expected increase in major bleeding in patients receiving anticoagulation (HR 2.10; 95% CI 1.30-3.38; p=0.002). ECG-diagnosed atrial fibrillation developed in 462/2536 patients (18%; 8.7%/year).
The NOAH-AFNET 6 trial found that oral anticoagulation in patients with AHRE increases bleeding without reducing a composite outcome of stroke, systemic embolism, or cardiovascular death.
https://www.nejm.org/doi/full/10.1056/NEJMoa2303062
1. Toennis T, Bertaglia E, Brandes A, et al. The influence of atrial high-rate episodes on stroke and cardiovascular death: an update. Europace. 2023. https://doi.org/10.1093/europace/euad166
2. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2020;42:373-498.
