Clinical Pearls & Morning Reports
Published September 27, 2023
Kirchhof et al. conducted a placebo-controlled trial that assessed the efficacy and safety of oral anticoagulant therapy with the non–vitamin K antagonist edoxaban in patients with atrial high-rate episodes — but without electrocardiogram-documented atrial fibrillation — who had clinical risk factors for stroke. Read the NEJM Original Article here.
Q: What are atrial high-rate episodes (AHREs)?
A: Implanted cardiac devices allow the continuous monitoring of cardiac rhythm. They can record short episodes of atrial arrhythmias by means of intracardiac or subcutaneous sensors. Arrhythmias detected by this type of continuous rhythm monitoring are referred to as subclinical atrial fibrillation or atrial high-rate episodes (AHREs). AHREs resemble atrial fibrillation but are rare and brief.
Q: Are AHREs typically treated?
A: Because cardiac electrical activity recorded during AHREs resembles that recorded during atrial fibrillation, some clinicians have initiated oral anticoagulant therapy in patients with AHREs, especially in those who have several clinical risk factors for stroke or in those who have AHREs that last longer than 24 hours. Whether the occurrence of AHREs in patients without atrial fibrillation (as documented on a conventional electrocardiogram) justifies the initiation of anticoagulants is not known.
A: The trial enrolled 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. 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 (the primary efficacy outcome) as compared with placebo, but it led to a higher incidence of a composite of death or major bleeding (the safety outcome). A primary efficacy outcome event occurred in 83 of 1270 patients (3.2% per patient-year) in the edoxaban group and in 101 of 1266 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 of 1270 patients (5.9% per patient-year) in the edoxaban group and in 114 of 1266 patients (4.5% per patient-year) in the placebo group (hazard ratio, 1.31; 95% CI, 1.02 to 1.67; P = 0.03).
A: This trial has several limitations. It 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. Owing to the premature termination of the trial after the accrual of 184 of the 220 originally planned primary efficacy outcome events, the trial does not have sufficient power to detect or rule out a small beneficial effect of oral anticoagulation on the prevention of stroke. The generalizability of the trial findings with edoxaban to other non-vitamin K antagonist oral anticoagulants is not known. Ongoing trials have been designed to determine the efficacy and safety of non-vitamin K antagonist oral anticoagulant therapy after successful rhythm-control therapy and to evaluate the safety and efficacy of apixaban in patients with AHREs. Similar trials may be warranted to evaluate the efficacy and safety of oral anticoagulation in patients who have rare atrial arrhythmias as detected by consumer electronics but do not have atrial fibrillation as documented on an ECG. This trial enrolled predominantly White patients in Europe; results may differ in other racial and ethnic groups.