Use of digoxin for heart failure and atrial fibrillation in elderly patients

Abstract

Background: Digoxin has been reported to improve symptoms and reduce hospitalization in patients with heart failure as well as to control rapid ventricular rate in patients with atrial fibrillation. Both of these are high-prevalence diseases in the elderly, and yet studies have indicated that digoxin may not be used appropriately in this population. Clinical trials evaluating digoxin use specifically in the elderly are scarce.

Objective: This article discusses the evidence on the therapeutic use of digoxin in the elderly and the changes in the pharmacokinetics of digoxin with aging to provide recommendations about the appropriate use of this drug in this population.

Methods: Peer-reviewed clinical trials, review articles, and relevant treatment guidelines limited to those evaluating patients aged >65 years were identified from MEDLINE and the Current Contents database (both from 1966 to May 1, 2010) using the search terms digoxin, pharmacokinetics, heart failure, and atrial fibrillation. Citations from available articles were also reviewed for additional references.

Results: One pharmacokinetic study, 8 clinical trials, and 2 guidelines were identified as relevant to digoxin use specifically in the elderly. In an elderly population (aged ≥65 years; n = 7) compared with a younger population (aged <65 years; n = 6), the elderly had a significant increase in digoxin t(1/2) (mean [SD]: oral dosing, 69.6 [13.1] vs 36.8 [4.5] hours; N dosing, 68.8 [12.3] vs 38.2 [3.5] hours; both, P < 0.05) and a decrease in total-body clearance (0.8 [0.2] vs 1.7 [0.2] mL/min/kg; P < 0.05). The use of digoxin in heart failure has been found to reduce the risk of hospitalization (risk ratio = 0.72; 95% CI, 0.66-0.79; P < 0.001). This beneficial effect of digoxin was found to be not significantly different across age groups in those aged >18 years. In terms of atrial fibrillation, the ability of digoxin to control the ventricular rate is believed to be caused by its vagotonic effect on the atrioventricular node. Therefore, digoxin is recommended for ventricular rate control only in patients with heart failure or sedentary lifestyle (ie, low sympathetic tone), or in those who cannot tolerate other rate-control agents. Because the prevalence of heart failure is high among the elderly (15.2 per 1000 population at age 65-74 years, 31.7 per 1000 population at age 75-84 years, and 65.2 per 1000 population at age ≥85 years), many of whom have a relatively sedentary lifestyle, digoxin may be an appropriate agent for ventricular rate control in the elderly.

Conclusions: The elderly population appears to gain comparable benefits as does a younger population from the use of digoxin for heart failure management in terms of symptom improvement and reduction of hospitalization. In atrial fibrillation, digoxin does not control the ventricular rate as efficaciously during exercise and in high adrenergic states as do R-blockers and calcium channel blockers. The elderly have reduced elimination of digoxin, so if digoxin is to be used, the dosing strategy must be conservative and therapeutic monitoring is needed. Further clinical studies are needed to confirm the pharmacokinetic parameters of digoxin in elderly patients with heart failure and/or atrial fibrillation.