NOAH-AFNET 6: Does the duration of AHRE influence response to edoxaban?

A subanalysis of the NOAH-AFNET 6 trial did not reveal interactions between the duration of atrial high-rate episodes (AHRE) and the use of the direct oral anticoagulant (DOAC) edoxaban on key safety and efficacy endpoints in patients with AHRE and stroke risk factors.

The previously published, double-blind, double-dummy NOAH-AFNET 6 study (NCT02618577) showed that the DOAC edoxaban did not substantially decrease a composite outcome of stroke, systemic embolism, or cardiovascular death compared with placebo in patients with AHRE and stroke risk factors [1]. However, major bleeding was more common in the edoxaban group. “Observational studies suggest a higher stroke risk associated with AHRE that last 24 hours or longer,” said Dr Nina Becher (University of Hamburg, Germany) [2–4]. “Randomised data evaluating anticoagulation in patients with long AHRE are, however, lacking.”

In the current sub-analysis of the NOAH-AFNET 6 trial, Dr Becher and her team compared the efficacy and safety of edoxaban between participants with AHRE lasting ≥24 hours (n=259) and participants with shorter duration AHRE (n=2,130) [2]. The primary efficacy endpoint was a composite of stroke, systemic embolism, or cardiovascular death, and the primary safety outcome was a composite of International Society on Thrombosis and Haemostasis (ISTH) major bleeding and all-cause death.

No significant interaction effect was found between treatment allocation and the duration of AHRE on the primary efficacy outcome (P_interaction=0.65). Similarly, no interaction was observed between treatment randomisation and the duration of AHRE on the main safety outcome (P_interaction=0.96). “These results were consistent using AHRE as a continuous variable or using median AHRE duration,” added Dr Becher. Finally, participants with long-duration AHRE had a higher ECG-diagnosed atrial fibrillation rate per patient-year than those with short-duration AHRE (17.0% vs 8.2%; HR 2.20; 95% CI 1.71–2.84; P<0.001). According to Dr Becher, regular ECGs are thus warranted in patients with AHRE lasting ≥24 hours.

“This was the first randomised comparison of oral anticoagulation and placebo in patients with AHRE lasting ≥24 hours. The number of ischaemic events was too small to rule out effects of anticoagulation on stroke prevention,” concluded Dr Becher.

1. 
   
   1. Kirchhof P, et al. N Engl J Med 2023;389:1167–1179.
   2. Becher N, et al. Efficacy and safety of anticoagulation with edoxaban in patients with atrial high rate episodes (AHRE) durations ≥ 24 hours: the NOAH-AFNET 6 trial. LB05, AHA Scientific Sessions 2023, 10-12 November, Philadelphia, PA, USA.
   3. Uittenbogaart SB, et al. Europace. 2018;20(9):1420–1427.
   4. Van Gelder IC, et al. Eur Heart J. 2017;38(17):1339–1344.

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Posted on 29 January 202430 January 2024