Should we use anticoagulation in AHRE to prevent stroke?

In a phase 3 trial, edoxaban did not reduce a composite outcome of stroke, systemic embolism, or cardiovascular death in patients with atrial high-rate episodes (AHRE), and it increased the risk for major bleeding. These NOAH-AFNET 6 trial results suggest that patients with AHRE are better managed without anticoagulation therapy until atrial fibrillation (AF) is diagnosed.

Prof. Paulus Kirchhof (University Heart & Vascular Center Hamburg, Germany) and his colleagues hypothesised that the oral anticoagulant edoxaban would prevent stroke and systemic embolism in patients with AHRE [1,2]. From 206 sites across Europe, they enrolled 2,536 patients with AHRE, either older than 65 years and with at least 1 additional stroke risk factor or older than 75 years of age, and randomised them 1:1 to edoxaban or a placebo. The primary endpoint of this phase 3 trial, named NOAH-AFNET 6 (NCT02618577), was a composite of stroke, systemic embolism, or cardiovascular death. The trial was unanimously terminated after 184 of the planned 220 primary outcome events had occurred.

After a median follow-up of 21 months, 3.3% of the participants in the edoxaban arm experienced a primary outcome event compared with 4.0% in the placebo arm (adjusted HR 0.81; 95% CI 0.60–1.08; P=0.15). As expected, the safety outcome of major bleeding or death favoured the placebo arm over the edoxaban arm with 114 versus 149 events (HR 1.31; 95% CI 1.02–1.67; P=0.03). This effect was predominantly driven by a higher rate of major bleeding in the experimental arm (adjusted HR 2.10; P=0.002). “The stroke rates were low with or without anticoagulation (0.9% vs 1.1%),” noted Prof. Kirchhof, “and we can’t prevent what does not occur” [1].

Based on these results, the researchers suggest that patients with AHRE should not be managed with anticoagulation therapy until AF is confirmed by ECG. Also, novel methods are needed to estimate the risk of stroke in patients with rare atrial arrhythmias like AHRE.

1. 
   
   1. Kirchhof P, et al. Anticoagulation with edoxaban in patients with atrial high-rate episodes (AHRE): results of the NOAH-AFNET 6 trial. Hot Line Session 1, ESC Congress 2023, 25–28 August, Amsterdam, the Netherlands.
   2. Kirchhof P, et al. N Engl J Med 2023; Aug 25. DOI: 10.1056/NEJMoa2303062.

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Posted on 30 October, 202330 October, 2023