Edoxaban increased major bleeding risk and didn’t reduce a composite outcome of stroke, systemic embolism, or CV death in patients with a rare atrial arrythmia.

In a phase 3 trial, edoxaban did not reduce a composite outcome of stroke, systemic embolism, or cardiovascular death in patients with atrial high-rate episodes (AHRE) but did come at the expense of an increased risk for major bleeding. These results, presented at ESC Congress 2023, suggest that patients with AHRE should be managed without anticoagulation therapy until atrial fibrillation is diagnosed.

Paulus Kirchhof, MD, and colleagues hypothesized that the oral anticoagulant edoxaban prevents stroke and systemic embolism in patients with AHRE. They randomly assigned 2,536 patients with AHRE, either older than 65 years and with at least one additional stroke risk factor, or older than 75 years, from 206 sites across Europe 1:1 to receive either edoxaban or placebo. The primary endpoint of this phase 3 trial, named NOAH-AFNET 6, was a composite of stroke, systemic embolism, or cardiovascular death. The trial was unanimously terminated after 184 of the planned 220 primary outcome events had occurred.

After a median follow-up of 21 months, 3.3% of the participants in the edoxaban arm experienced a primary outcome event, compared with 4.0% in the placebo arm (adjusted HR, 0.81; 95% CI, 0.60–1.08; P=0.15). As expected, the safety outcome of major bleeding or death favored the placebo arm over the edoxaban arm with 114 versus 149 events (HR 1.31; 95% CI, 1.02–1.67; P=0.03). This effect was predominantly driven by a higher rate of major bleedings in the experimental arm (adjusted HR, 2.10; P=0.002). “The stroke rates were low with or without anticoagulation (0.9% vs 1.1%),” noted Dr. Kirchhof, “and we can’t prevent what does not occur.”

Based on these results, the researchers suggest that patients with AHRE should not be managed with anticoagulation therapy until atrial fibrillation is confirmed by ECG. Also, novel methods are needed to estimate the risk for stroke in patients with rare atrial arrhythmias like AHRE.

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