Non-recommended dosing occurs in ~25-50% of non-vitamin K antagonist oral anticoagulant prescriptions, with limited data for edoxaban. We analyzed edoxaban dosing patterns in atrial fibrillation patients from the Global ETNA-AF program, relating patterns to baseline characteristics and 1-year clinical outcomes. The following dosing groups were compared: non-recommended 60 mg ("overdosed") vs. recommended 30 mg; non-recommended 30 mg ("underdosed") vs. recommended 60 mg. Most (22,166/26,823; 82.6%) patients received recommended doses. Non-recommended dosing was more frequent near label-specified dose-reduction thresholds. Ischemic stroke (IS; HR 0.85, 95% CI 0.50-1.47; p = 0.6) and major bleeding (MB; HR 1.47, 95% CI 0.97-2.71; p = 0.07) did not differ between recommended 60 mg and "underdosed" groups, whereas all-cause (HR 1.61, 95% CI 1.23-2.08; p = 0.0003) and cardiovascular deaths (HR 1.61, 95% CI 1.11-2.38; p = 0.01) were higher in the "underdosed" group. Compared with recommended 30 mg, the "overdosed" group had lower IS (HR 0.51, 95% CI 0.28-0.98; p = 0.04) and all-cause death (HR 0.74, 95% CI 0.55-0.98; p = 0.03) without higher MB (HR 0.74, 95% CI 0.46-1.22; p = 0.2). In conclusion: non-recommended dosing was infrequent, but more common near dose-reduction thresholds. "Underdosing" was not associated with better clinical outcomes. The "overdosed" group had lower IS and all-cause death without higher MB.
