Background and Aims Patients with long atrial high-rate episodes (AHREs) >= 24 h and
stroke risk factors are often treated with anticoagulation for stroke prevention.
Anticoagulation has never been compared with no anticoagulation in these patients.
Methods This secondary pre-specified analysis of the Non-vitamin K antagonist Oral
anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined
interactions between AHRE duration at baseline and anticoagulation with edoxaban compared
with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome
was a composite of stroke, systemic embolism, or cardiovascular death. The safety
outcome was a composite of major bleeding and death. Key secondary outcomes were components
of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. Results
Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE
>= 24 h were present at baseline in 259/2389 patients (11%, 78 +/- 7 years old, 28%
women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients
with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE >= 24
h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients
treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration
did not interact with the efficacy (P-interaction = .65) or safety (P-interaction
= .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed
this. Patients with AHRE >= 24 h developed more ECG-diagnosed atrial fibrillation
(17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001).
Conclusions This hypothesis-generating analysis does not find an interaction between
AHRE duration and anticoagulation therapy in patients with device-detected AHRE and
stroke risk factors. Further research is needed to identify patients with long AHRE
at high stroke risk.
