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Hot Line: To anticoagulate or not in patients with atrial high-rate episodes without AF?

26 Aug 2023

While atrial high-rate episodes (AHRE) are associated with an increased risk of stroke, the risk is known to be lower than with atrial fibrillation (AF).1 ESC guidelines recommend oral anticoagulation to prevent stroke in patients with AF and increased stroke risk, but propose individualised decisions in patients with AHRE but without ECG-documented AF.2

As presented by Professor Paulus Kirchhof (University Heart & Vascular Center Hamburg - Hamburg, Germany) in a Hot Line session yesterday, the investigator-driven double-blind NOAH-AFNET 6 trial is the first to investigate the efficacy and safety of oral anticoagulation in patients with AHRE, but without ECG-documented AF.1

Across 18 European countries, patients were eligible for inclusion if they were aged 65 years with AHRE episodes 6 minutes detected by implantable devices, and with at least one additional stroke risk factor (heart failure, hypertension, diabetes, prior stroke or transient ischaemic attack, vascular disease or age 75 years). Participants were randomised to anticoagulation or no anticoagulation. Anticoagulation consisted of edoxaban in the dose approved for stroke prevention in AF (60 mg once daily with a reduction to 30 mg once daily according to approved dose-reduction criteria). No anticoagulation consisted of placebo or aspirin 100 mg once daily in patients with an indication for antiplatelet therapy.

The primary analysis was conducted in 2,536 patients who had a mean age of 78 years and median CHA2DS2-VASc score of 4. The median AHRE duration at baseline was 2.8 hours without an upper limit and 97% of AHRE showed atrial rates >200 beats per minute, clearly resembling AF.

The trial was stopped early due to safety signals and a trend towards futility for efficacy after enrolment of all planned patients.

There was no significant difference between groups for the primary efficacy outcome – a composite of stroke, systemic embolism or CV death – which occurred in 83 patients in the anticoagulation group (3.2%/year) and in 101 patients in the no anticoagulation group (4.0%/year) (hazard ratio [HR] 0.81; 95% CI 0.6 to 1.1; p=0.15). The stroke rate was low both with anticoagulation (0.9%/year) and without (1.1%/year). The primary safety outcome – a composite of major bleeding and all-cause death – occurred in 149 patients in the anticoagulation group (5.9%/year) and in 114 patients in the no anticoagulation group (4.5%/year) (HR 1.3; 95% CI 1.0 to 1.7; p=0.03). The difference in safety outcomes was driven by an increase in major bleeding in patients receiving anticoagulation (HR 2.10; 95% CI 1.30 to 3.38; p=0.002). Around one-fifth of participants (18%) developed ECG-diagnosed AF (8.7%/year).

Summarising the findings, Prof. Kirchhof comments: “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 CV death. 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 to demand ECG documentation of AF 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.”


  1. Kirchhof P, et al. Am Heart J. 2017;190:12–18.
  2. Hindricks G, et al. Eur Heart J. 2020;42:373–498.