Oral anticoagulants did not improve efficacy or safety in patients with atrial high rate episodes (AHRE), but without electrocardiogram (ECG)-diagnosed atrial fibrillation (AFib), according to results from the NOAH-AFNET 6 trial presented at ESC Congress 2023 and simultaneously published in the New England Journal of Medicine.

The trial randomized 2,536 patients (mean age of 65 years) with AHRE episodes ≥6 minutes detected by implantable devices to receive either edoxaban or placebo. Patients randomized to edoxaban received 60 mg once daily, reduced to 30 mg once daily according to approved dose reduction criteria for stroke prevention in AFib. Patients assigned to the placebo group and who had an indication for antiplatelet therapy received aspirin 100 mg once daily. All patients had at least one additional stroke risk factor, including heart failure, hypertension, diabetes, prior stroke or transient ischemic attack, vascular disease, or age ≥75 years, and were outside the approved indication of edoxaban.

The trial's primary efficacy outcome, which was a composite of stroke, systemic embolism, or cardiovascular death, occurred in 83 patients in the anticoagulation group (3.2%/year) and in 101 patients in the no anticoagulation group (4.0%/year). Stroke rates were low across both groups – 0.9%/year in the edoxaban group and 1.1%/year in the placebo group.

The primary safety outcome – a composite of major bleeding and all-cause death – occurred in 149 patients in the edoxaban group (5.9%/year) and in 114 patients in the placebo group (4.5%/year). Researchers noted that the difference in safety outcomes was driven by an expected increase in major bleeding in patients receiving anticoagulation. The trial was stopped early due to safety signals and a trend towards futility for efficacy after enrollment of all planned patients.

"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," said Paulus Kirchhof, MD, the trial's principal investigator. "The increased bleeding on anticoagulation therapy was expected. The low stroke rate with and without anticoagulation was unexpected. The results of NOAH-AFNET 6 clearly suggest the need to demand ECG documentation of AFib prior to initiation of oral anticoagulation. Further research is needed to better understand the stroke risk in patients with very rare and short atrial arrhythmias."

Clinical Topics: Anticoagulation Management

Keywords: ESC Congress, ESC23, Anticoagulants, ACC International

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