Background: Digoxin has a narrow therapeutic window. A target serum digoxin concentration of ≤0.9 ng/mL is recommended for heart failure (HF). However, the appropriate serum digoxin concentration for HF patients with atrial fibrillation (AF) is not fully established. This study aimed to evaluate the relationship between the serum concentration and clinical outcome in patients with HF and AF receiving digoxin.

Methods: This single-center retrospective study included 348 patients with HF and AF receiving digoxin between 2008 and 2016 (median age, 68 years; female, 37％). The median follow-up period was 596 days. The clinical outcomes were all-cause death and digoxin intoxication. The patients were classified into 4 groups based on the digoxin trough concentration one month after the start of treatment: ＜0.60 ng/mL, 0.60-0.89 ng/mL, 0.90-1.19 ng/mL, and ≥1.20 ng/mL.

Results: The median digoxin dosage was 0.125 mg daily, and the median serum trough concentration of digoxin was 0.77 ng/mL. The incidence of all-cause death was not significantly different among the concentration groups. Multivariate analysis showed that serum digoxin concentrations ≥0.9 ng/mL were not associated with mortality. Using a modified Rosendaal linear interpolation method, the incidence of all-cause death did not increase with higher serum digoxin concentrations. Cardiac disturbance was observed in any of the concentration groups, but gastrointestinal symptoms were observed in patients with a serum digoxin concentration of ≥0.90 ng/mL.

Conclusions: Our results showed that all-cause death did not occur in a concentration-dependent manner in patients with HF and AF. Gastrointestinal symptoms due to digoxin intoxication but not cardiac disturbance increased with higher serum concentrations.