From the Guidelines
Digoxin should be considered for contractility support in patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal therapy with first-line agents, such as beta-blockers, ACE inhibitors, and SGLT2 inhibitors. According to the 2013 ACCF/AHA guideline for the management of heart failure 1, digoxin may be added to the initial regimen in patients with severe symptoms who have not yet responded symptomatically during guideline-directed medical therapy (GDMT). The typical maintenance dose ranges from 0.125 to 0.25 mg daily, though lower doses (0.125 mg daily or even every other day) are often used in elderly patients or those with impaired kidney function, as recommended by the 2009 ACCF/AHA Heart Failure Guidelines 2.
Key considerations for the use of digoxin include:
- Careful monitoring of serum digoxin levels (therapeutic range is 0.5 to 1.0 ng per mL, as suggested by the 2009 ACCF/AHA Heart Failure Guidelines 2) and electrolytes, particularly potassium, as hypokalemia increases the risk of digoxin toxicity
- Monitoring for signs of toxicity, including nausea, vomiting, visual disturbances, and cardiac arrhythmias
- Avoiding use in patients with significant sinus or atrioventricular block unless the block has been addressed with a permanent pacemaker
- Using cautiously in patients taking other drugs that can depress sinus or atrioventricular nodal function or affect digoxin levels, such as amiodarone or a beta blocker, as noted in both the 2009 2 and 2013 1 guidelines.
Overall, while digoxin does provide positive inotropic support, its use is generally reserved for patients who remain symptomatic despite optimal therapy with first-line agents, due to the greater mortality benefits associated with these newer medications.
From the FDA Drug Label
Digoxin is one of the cardiac (or digitalis) glycosides, a closely related group of drugs having in common specific effects on the myocardium. These drugs are found in a number of plants. Digoxin is extracted from the leaves of . The term “digitalis” is used to designate the whole group of glycosides The glycosides are composed of two portions: a sugar and a cardenolide (hence “glycosides”). Digoxin affects contractility and excitability of the heart in a manner similar to that of calcium.
Contractility Support:
- Digoxin is used for its effects on the myocardium, which includes contractility support.
- The drug affects contractility and excitability of the heart.
- It is used to treat conditions such as heart failure and atrial arrhythmias.
- However, its use should be cautious in certain conditions, such as acute myocardial infarction and electrolyte disorders 3.
From the Research
Digoxin for Contractility Support
- Digoxin is used to increase myocardial contractility in patients with heart failure, particularly those with atrial fibrillation and a rapid ventricular response 4.
- It has a modest but durable beneficial effect in congestive heart failure due to impaired left ventricular systolic function 4.
- However, comparative studies have shown that ACE inhibitors have greater benefits and tolerability than digoxin in patients with mild to moderate heart failure 4.
- Digoxin should be reserved for patients with atrial fibrillation and a rapid ventricular response, and for those whose heart failure is not controlled with an ACE inhibitor plus a diuretic 4.
Safety and Efficacy of Digoxin
- The safety and efficacy of digoxin in patients with heart failure and atrial fibrillation are unclear, with conflicting results from observational analyses and meta-analyses 5.
- Digoxin should be used with caution in patients with atrial fibrillation and heart failure, as it may be associated with worse outcomes in patients without heart failure 5.
- The impact of digoxin on all-cause mortality and adverse effects in patients with atrial fibrillation and heart failure remains unclear, and more trials are needed to evaluate its effects 5.
Pharmacology and Toxicology of Digoxin
- Digoxin has a narrow therapeutic window and is a toxic substance with well-known cardiotoxic effects 6.
- Its pharmacokinetics, pharmacodynamics, and acute toxicity data are summarized in the literature, and its treatment side effects and human poisonings are thoroughly discussed 6.
- A comprehensive review of digoxin's use in atrial fibrillation, congestive heart failure, and post-myocardial infarction highlights its limited role in contemporary medicine 7.
- Digoxin dosing should be based on patient-specific factors, and its use should be guided by an understanding of its unique pharmacokinetic profile and narrow therapeutic index 8.