From the Guidelines
Digoxin is not recommended as a primary therapy for patients with Congestive Heart Failure (CHF) and normal Left Ventricular Ejection Fraction (LVEF). The primary issue in these patients is diastolic dysfunction rather than systolic dysfunction, and digoxin's mechanism of action (increasing contractility) is less relevant in this context 1. Instead, management should focus on controlling underlying conditions like hypertension, managing fluid overload with diuretics, and addressing other contributing factors such as atrial fibrillation if present.
Key Considerations
- The benefit of digoxin in patients with HF remains controversial, and its use should be optimized with guideline-directed medical therapy (GDMT) before considering its addition 1.
- Digoxin may be considered in patients with persistent symptoms of HF despite GDMT, but its use should be cautious and with close monitoring of serum levels (target 0.5-0.9 ng/mL) due to its narrow therapeutic window and risk of toxicity 1.
- Side effects of digoxin can include nausea, visual disturbances, confusion, and potentially life-threatening arrhythmias, especially in elderly patients or those with renal impairment.
Management Priorities
- Controlling underlying conditions like hypertension
- Managing fluid overload with diuretics
- Addressing other contributing factors such as atrial fibrillation if present
- Prioritizing guideline-directed therapies including diuretics for symptom relief, blood pressure control, and management of comorbidities rather than digoxin as a primary therapy 1.
Monitoring and Safety
- Close monitoring of serum digoxin levels is necessary to minimize the risk of toxicity, especially in elderly patients or those with renal impairment 1.
- The risk of death is independently associated with serum digoxin concentration, with a significantly higher risk observed in those with concentrations ≥1.2 ng/mL and ≥1.6 ng/mL 1.
From the FDA Drug Label
Digoxin produces hemodynamic improvement in patients with heart failure. Short- and long-term therapy with the drug increases cardiac output and lowers pulmonary artery pressure, pulmonary capillary wedge pressure, and systemic vascular resistance These hemodynamic effects are accompanied by an increase in the left ventricular ejection fraction and a decrease in end-systolic and end-diastolic dimensions The Digitalis Investigation Group (DIG) main trial was a multicenter, randomized, double-blind, placebo-controlled mortality study of 6801 patients with heart failure and left ventricular ejection fraction ≤0. 45. In situations where there is no statistically significant benefit of treatment evident from a trial’s primary endpoint, results pertaining to a secondary endpoint should be interpreted cautiously.
INDICATIONS AND USAGE Digoxin is indicated for the treatment of mild to moderate heart failure.
Digoxin increases left ventricular ejection fraction and improves heart failure symptoms as evidenced by exercise capacity and heart failure-related hospitalizations and emergency care, while having no effect on mortality.
The answer to whether patients with Congestive Heart Failure (CHF) and normal Left Ventricular Ejection Fraction (LVEF) should be taking digoxin is not directly supported by the provided drug labels, as the studies mentioned, such as the Digitalis Investigation Group (DIG) main trial, specifically involved patients with left ventricular ejection fraction ≤0.45 2. Therefore, no conclusion can be drawn for patients with normal LVEF. Key points to consider include:
- The primary benefits of digoxin observed in clinical trials were in patients with reduced ejection fraction.
- The drug labels do not provide direct evidence for the use of digoxin in patients with CHF and normal LVEF 2. Given the lack of direct evidence, a conservative clinical decision would be to not recommend digoxin for patients with CHF and normal LVEF, as the benefits of the drug in this specific population are not established 2.
From the Research
Digoxin Use in Congestive Heart Failure (CHF) Patients
- The use of digoxin in patients with CHF and normal Left Ventricular Ejection Fraction (LVEF) is a topic of discussion among clinicians and researchers.
- According to a study published in 1995 3, digoxin should not be given to patients with CHF in sinus rhythm with normal LVEF.
- A more recent study from 2020 4 found that digoxin initiation prior to hospital discharge was not associated with 30-day or 6-year outcomes in older hospitalized patients with Heart Failure with Preserved Ejection Fraction (HFpEF).
Efficacy and Safety of Digoxin
- Studies have shown that digoxin can reduce the risk of heart failure hospitalization in patients with Heart Failure with Reduced Ejection Fraction (HFrEF) 5, 6.
- However, the efficacy and safety of digoxin in patients with HFpEF are less clear, with one study finding no association with 30-day or 6-year outcomes 4.
- Another study published in 2016 7 highlighted the methodological issues and limitations of individual studies on the efficacy and safety of digoxin in heart failure patients with reduced ejection fraction.
Clinical Guidelines and Recommendations
- The American and European heart failure guidelines list digoxin as a valid therapeutic option for heart failure patients with reduced ejection fraction 7.
- However, the use of digoxin in patients with CHF and normal LVEF is not recommended, except in cases of supraventricular tachyarrhythmias or in patients who cannot tolerate other therapies 3.