1. In this randomized controlled trial, edoxaban did not significantly reduce the incidence of a composite of cardiovascular death, stroke, or systemic embolism compared to placebo in atrial high-rate episodes (AHREs).
2. Edoxaban was associated with a higher incidence of a composite of death or major bleeding as compared to a placebo.
Evidence Rating Level: 1 (Excellent)
Study Rundown: AHREs are arrhythmias that can be detected by implanted cardiac devices that allow for continuous cardiac rhythm monitoring. Cardiac electrical activity recorded during AHREs resembles atrial fibrillation. Accordingly, clinicians may initiate oral anticoagulant therapy in patients with AHREs. This is mainly seen in patients with risk factors for stroke. However, there is a knowledge gap in understanding the efficacy and safety of oral anticoagulant therapy with the non–vitamin K antagonist edoxaban in patients with AHREs who have clinical risk factors for stroke. Overall, this study found that the incidence of a composite of cardiovascular death, stroke, or systemic embolism with edoxaban was not significantly different from that with a placebo. Notably, treatment with edoxaban led to a higher incidence of a composite of death or major bleeding. The premature termination of the trial was a major limitation of its data analysis. Nevertheless, these study’s findings are significant, as they demonstrate that treatment with edoxaban in patients with AHREs without atrial fibrillation did not improve composite cardiovascular death, stroke, or systemic embolism but did increase the risk of composite death or major bleeding.
Click to read the study in NEJM
Relevant Reading: Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR
In-Depth [randomized controlled trial]: This event-driven, double-blinded, randomized controlled trial was conducted in 18 European countries. Patients 65 years of age or older with AHREs detected by implanted devices and no history of atrial fibrillation as documented on an electrocardiogram and with risk factors for stroke were eligible for the study. Patients who had atrial fibrillation as documented on an electrocardiogram; acute coronary syndrome, percutaneous coronary intervention, or coronary bypass surgery within 30 days of enrollment; a life expectancy of less than 12 months; a contraindication to oral anticoagulation or to edoxaban; an indication for dual antiplatelet therapy; and indications for oral anticoagulation were excluded from the study. The primary outcome measured was the first occurrence of a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. Outcomes in the primary analysis were assessed via a modified intention-to-treat protocol with a cause-specific Cox proportional hazards model. Based on the analysis, a primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.60 to 1.08). 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 114 patients (4.5% per patient-year) in the placebo group (hazard ratio, 1.31; 95% CI, 1.02 to 1.67). In summary, this study demonstrates that in patients with AHREs and risk factors for stroke, edoxaban did not significantly reduce the incidence of a composite of cardiovascular death, stroke, or systemic embolism as compared with placebo and did lead to a higher incidence of a composite of death or major bleeding.
Image: PD
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