NOAH-AFNET 6: AHRE>24 hours associated with low stroke risk but more likely to develop AF later

By Lucas Marinacci on

Key Points

  • This pre-specific subanalysis of NOAH-AFNET 6 found that those with long lasting atrial high rate episodes >24 hours were more likely to develop atrial fibrillation (AF); there was no significant interaction found between the duration of the longest AHRE and the efficacy and safety of oral anticoagulation.

The double-blinded, double dummy NOAH-AFNET 6 trial randomized elderly patients with device-detected AHREs and a median CHA2DS2VASC of 4—but without an ECG diagnosis of AF—to edoxaban or placebo.  It was stopped early for a trend towards increased bleeding in the anticoagulation arm without a difference in stroke rates.1

On November 12, 2023, Dr. Nina Becher presented the results of a pre-specific sub-analysis of NOAH-AFNET 6 entitled “Anticoagulation with Edoxaban in Patients with Long Atrial High-Rate Episodes >= 24 Hours” at a Late Breaking Science Session of the American Heart Association Scientific Sessions in Philadelphia, PA, with simultaneous publication in European Heart Journal.2

The purpose of this prespecified sub-analysis of NOAH-AFNET 6 was to assess the efficacy and safety of edoxaban compared to no anticoagulation among those with AHRE lasting >=24 hours versus those with shorter episodes.  While observational data suggests a higher stroke risk associated with longer AHREs, randomized data to support anticoagulation in patients with longer AHRE are lacking.

Overall, 2130 patients had AHRE <24 hours, with 1062 receiving edoxaban and 1068 receiving placebo, while 259 had AHRE > 24 hours, with 132 receiving edoxaban and 127 receiving placebo.  The overall mean age was 78 years with a median CHADS2AVSC score of 4 and median HAS-BLED Score of 3.  Those who were in the AHRE>= 24 hour group also had a more total AHRE events.  

There was no significant difference change in the primary composite efficacy outcome of ischemic stroke, systemic embolism, or cardiovascular death between the placebo and edoxaban groups based on AHRE duration of >= 24 hours (p-value for interaction of 0.65).  There was also no significant change noted in each of the individual components.  These results were consistent when AHRE was used as a continuous variable or using median AHRE duration.  There was also no significant difference noted in the composite safety outcome of major bleeding or death.  Those with AHRE duration >= 24 hours had a significantly higher incidence of ECG-diagnosed AF (assessed every 6 months per study protocol; HR 2.20; 95% CI 1.71,2.84, p<0.001).  The authors noted that this population was primarily White and the number of ischemic events was too small to rule out effects of anticoagulation on stroke prevention.

According to Dr. Nina Becher of University Hospital Hamburg-Eppendorf: “In this prespecified sub-analysis of the NOAH-AFNET 6 trial, the rate of stroke appeared low in patients with AHRE durations ≥24 hours and there was no interaction between the duration of the longest AHRE episode and the efficacy and safety of anticoagulation…Further research is needed to identify patients with AHRE at higher risk of stroke and other cardiovascular events.”


  1. Kirchhof P, Blank BF, Calvert M, et al. Probing oral anticoagulation in patients with atrial high rate episodes: Rationale and design of the Non–vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH–AFNET 6) trial. Am Heart J. 2017;190:12–18.
  2. Becher et al. Anticoagulation with edoxaban in patients with long Atrial High-Rate Episodes ≥24 hours. Eur Heart J. 2023. Published online2023.