Digoxin and Cognitive Performance in Patients with Heart Failure A Cohort, Pharmacoepidemiological Survey

Background: Cognitive dysfunction is a prevalent condition among patients with heart failure (HF), and is independently associated with disability and mortality. A large study of patients with atrial fibrillation incidentally demonstrated superior cognitive performance among participants who received digoxin. Interestingly, endogenous cerebral digoxin influences neuronal Na+-dependent transport of calcium and amino acids, as well as the release and reuptake of several neurotransmitters involved in cognitive functioning. Objective: To assess whether treatment with digoxin might improve cognition in patients with HF. Methods: This pharmacoepidemiological cohort study included hospitalized elderly people (age >= 65 years) from the GIFA (Gruppo Italiano di Farmacoepidemiologia nell'Anziano [Italian Group of Pharmacoepidemiology in the Elderly]) study. The GIFA study included 13 598 patients (1590 with a verified diagnosis of HF) without cerebrovascular or Alzheimer's disease. The main outcome measure was cognitive performance, which was assessed on admission and immediately before discharge using the Hodkinson Abbreviated Mental Test. The diagnosis of HF was verified by the study investigators. Results: Among participants with HF, cognitive performance improved in 25% of 1172 participants who received digoxin compared with 16% of remaining patients (p < 0.0001). Among participants without H-F, cognition improved in 23% of 2431 patients receiving digoxin compared with 17% of untreated patients (p < 0.0001). According to logistic regression analysis, the probability (odds ratio) of improving cognitive performance associated with administration of digoxin was 1.69 (95% Cl 1.20, 2.38) among patients with HF, and 1.13 (95% CI 0.98, 1.31) among patients without HF, after adjusting for potential confounders. Analysis of the interaction term 'use of digoxin by diagnosis of HF' in fully adjusted logistic regression confirmed (p = 0.018) that the association between use of digoxin and improving cognitive performance varied according to diagnosis of HF. Conclusion: Treatment with digoxin might selectively improve cognitive performance among older patients with HF.