Oral anticoagulation not the best bet for patients with atrial high-rate episodes

Patients with atrial high-rate episodes (AHRE) do not seem to benefit from anticoagulation with edoxaban, which has fallen short of reducing the composite outcome of stroke, systemic embolism, or cardiovascular death, according to the results of the NOAH-AFNET* 6 trial.

There was no difference in the number of the primary outcome events (ie, composite of stroke, systemic embolism, or cardiovascular death) that occurred among patients who received edoxaban and those who received placebo (3.2 percent vs 4.0 percent per year; hazard ratio [HR], 0.81, 95 percent confidence interval [CI], 0.6–1.1; p=0.15), reported principal investigator Prof Paulus Kirchhof of the University Heart & Vascular Center Hamburg in Hamburg, Germany. [Kirchhof P, et al, ESC Congress 2023]

Stroke rate, specifically, was low in both treatment groups (0.9 percent per year in the edoxaban group vs 1.1 percent per year in the placebo group).

As for safety, edoxaban treatment was associated with a threefold greater frequency of the composite of major International Society of Thrombosis and Haemostasis (ISTH) bleeding or all-cause death (5.9 percent vs 4.5 percent per year; HR, 1.3, 95 percent CI, 1.0–1.7; p=0.03). This difference, according to Kirchhof, was driven by an expected increase in major bleeding among patients receiving anticoagulation (HR, 2.10, 95 percent CI, 1.30–3.38; p=0.002).

Overall, 462 cases of ECG-diagnosed atrial fibrillation (AF) were documented during the study (8.7 percent per year).

Premature termination

“[NOAH-AFNET 6] was stopped early due to safety signals and a trend towards futility for efficacy after enrolment of all planned patients,” with a median follow-up of 21 months, Kirchhoff said.

A total of 2,536 patients (mean age 78 years, 37 percent women, median CHA₂DS₂-VASc score 4) who received at least one dose of study drug (edoxaban: n=1,270; placebo: n=1,266) comprised the primary, modified intention-to-treat analysis population. All patients had AHRE episodes that lasted ≥6 minutes and an atrial rate of ≥170 beats per minute. Other inclusion criteria were ≥65 years of age and the presence of at least one stroke risk factor (eg, heart failure, hypertension, diabetes, prior stroke, vascular disease, or age ≥75 years).

The median AHRE duration at baseline was 2.8 hours without an upper limit, and 97 percent of patients showed atrial rates >200 beats per minute, clearly resembling AF, Kirchhof noted.

“AF is often only detected after a first stroke, calling for earlier diagnosis to enable anticoagulation. Less time in AF may lower stroke risk,” he said, emphasizing the importance of early rhythm control therapy. [Stroke 2013;44:3357-3364; N J Engl Med 2013;370:2467-2477; Europace 2022;doi:10.1093/europace/euac062; N J Engl Med 2020; doi:10.1056/NEJMoa2019422; Eur Heart J 2022;43:4127-4144]

“The results of NOAH-AFNET 6 suggest to demand ECG documentation of AF prior to initiation of oral anticoagulation,” Kirchhof said.

Then again, the investigator acknowledged that the trial had no sufficient power to rule out a small effect of oral anticoagulation on cardiovascular events and that only one drug was tested. Furthermore, the trial was conducted in 18 European countries, so the effects in other ethnicities are unknown.

Kirchhof called for additional research to better understand the stroke risk in patients with very rare and short atrial arrhythmias.