Harms May Outweigh Benefits for Anticoagulation in Subclinical AF

A double-blind, double-dummy, randomized trial in European countries revealed that among patients with atrial high-rate episodes (AHREs) detected by implantable devices, anticoagulation with edoxaban led to a higher incidence of a composite of death or major bleeding but did not significantly improve efficacy outcomes. A total of 2536 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 were randomized in a 1:1 ratio to receive edoxaban or placebo (mean age 78 years, 37.4% women, with the median duration of AHREs 2.8 hours). The trial was terminated early, at a median follow-up of 21 months, based on 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 (a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis) 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). The incidence of stroke was approximately 1% per patient-year in both groups. A safety outcome event (a composite of death from any cause or major bleeding) 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). ECG-diagnosed atrial fibrillation developed in 462 of 2536 patients (18.2% total, 8.7% per patient-year). The findings suggest that anticoagulation should not be used in patients with AHREs until atrial fibrillation is documented by ECG. Source: https://www.nejm.org/