Use of digoxin in heart failure with reduced ejection fraction
- Wilson S Colucci, MD
Wilson S Colucci, MD
- Section Editor — Heart Failure
- Professor of Medicine
- Boston University School of Medicine
- Lynne Sylvia, PharmD
Lynne Sylvia, PharmD
- Senior Clinical Pharmacy Specialist, Tufts Medical Center
- Clinical Professor, Northeastern University, School of Pharmacy
Digitalis has been used for over 200 years to treat patients with heart failure (HF). Evidence from clinical trials supports the use of digoxin (the most widely used formulation of digitalis) to improve symptoms and reduce hospitalization in patients with HF with reduced left ventricular ejection fraction (LVEF ≤40 percent; HFrEF), particularly in patients with more advanced symptoms, but a survival benefit was not demonstrated [1,2]. (See 'Evidence' below.)
The use of digoxin in treating HFrEF will be reviewed here. The use of digoxin in this setting should be considered in the context of comprehensive management of HFrEF . (See "Overview of the therapy of heart failure with reduced ejection fraction".)
MECHANISM OF ACTION
Digoxin acts by inhibiting the Na-K-ATPase pump, thus reducing the transport of sodium from the intracellular space in myocytes  as well as noncardiac cells to the extracellular space . This mechanism contributes to digoxin’s hemodynamic, neurohumoral, and electrophysiologic effects .
Hemodynamic effects — In myocytes, increased intracellular sodium (resulting from Na-K-ATPase inhibition by digoxin) reduces sodium-calcium exchange (which normally causes calcium extrusion from the cell), leading to a rise in the intracellular calcium concentration. This results in improved isolated myocyte contractile performance (increased shortening velocity) and improved overall left ventricular (LV) systolic function [4,6].
Several small trials have examined the short-term hemodynamic efficacy of digoxin in patients with systolic HF using invasive monitoring [7-9]. These studies showed that the administration of 1 mg of intravenous digoxin resulted in an acute improvement in cardiac output, LV stroke work index, mean pulmonary capillary wedge pressure (PCWP), pulmonary artery diastolic pressure, and right atrial pressure, either at rest or with exercise.
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- MECHANISM OF ACTION
- Hemodynamic effects
- Neurohumoral effects
- Electrophysiologic effects
- Our approach
- - Worsened symptoms with digoxin withdrawal
- - Symptomatic benefit from digoxin
- When to avoid
- Evaluation for contraindications and cautions
- Baseline and follow-up testing
- Digoxin dosing
- - Standard initial dose
- - Nomogram-based method
- Digoxin level
- - When to check digoxin levels
- - Target level
- - How to monitor levels and adjust digoxin dose
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS