Is digoxin (digitalis) contraindicated in congestive heart failure (CHF)?

Digoxin is NOT Contraindicated in Congestive Heart Failure

Digoxin is not contraindicated in CHF; rather, it is a Class IIa/2b recommendation that may be considered in symptomatic patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite guideline-directed medical therapy (GDMT), primarily to reduce hospitalizations. 1

Current Guideline Recommendations

The 2022 AHA/ACC/HFSA guidelines provide a Class 2b recommendation (Level of Evidence B-R) stating that digoxin "might be considered to decrease hospitalizations for HF" in patients with symptomatic HFrEF despite GDMT or in those unable to tolerate GDMT. 1 This represents a measured endorsement—not a contraindication—though it reflects the drug's limited evidence base compared to modern neurohormonal antagonists.

The FDA label explicitly states digoxin is indicated for the treatment of mild to moderate heart failure, noting it increases left ventricular ejection fraction and improves heart failure symptoms and exercise capacity while reducing HF-related hospitalizations, though it has no effect on mortality. 2

Key Evidence Base

• The landmark DIG trial (which predated current GDMT) showed digoxin had no effect on mortality but modestly reduced the combined risk of death and hospitalization over 2-5 years in NYHA class II-III patients. 1

• Digoxin demonstrated a 25% reduction in hospitalizations for heart failure and a 28% reduction in the risk of having at least one HF hospitalization. 2

• The benefit in patients already on contemporary GDMT (ACE inhibitors/ARBs, beta-blockers, aldosterone antagonists) remains unclear since most trials preceded these therapies. 1

Actual Contraindications (Not CHF)

The true contraindications to digoxin are limited and specific: 2

• Ventricular fibrillation
• Known hypersensitivity to digoxin or other digitalis preparations
• Significant sinus or atrioventricular block unless addressed with a permanent pacemaker 1

Clinical Use Algorithm

When to consider digoxin:

• Patient has symptomatic HFrEF (LVEF ≤40-45%) despite optimization of GDMT (ACE inhibitor/ARB/ARNI, beta-blocker, aldosterone antagonist, SGLT2 inhibitor) 1
• Patient remains symptomatic (persistent dyspnea, exercise intolerance, or recurrent HF hospitalizations) 1
• Patient is unable to tolerate GDMT components 1
• Patient has concurrent atrial fibrillation requiring rate control (though beta-blockers are usually more effective) 1

Dosing considerations:

• Start at 0.125-0.25 mg daily 1
• Use lower doses (0.125 mg daily or every other day) if patient is >70 years old, has impaired renal function, or has low lean body mass 1
• Target serum digoxin concentration of 0.5-0.9 ng/mL (NOT the traditional 0.8-2.0 ng/mL range) 1
• Higher doses (0.375-0.50 mg daily) are rarely needed and potentially harmful 1

Critical Safety Considerations

Mortality risk is concentration-dependent: Retrospective analyses show a linear relationship between mortality and serum digoxin concentration, with significantly higher risk at concentrations ≥1.2 ng/mL and especially ≥1.6 ng/mL. 1 This explains why lower target ranges are now recommended.

Use caution with drug interactions: Concomitant use of amiodarone, clarithromycin, erythromycin, itraconazole, cyclosporine, propafenone, verapamil, or quinidine can increase serum digoxin concentrations and necessitate dose reduction. 1

Monitor for toxicity risk factors: Hypokalemia, hypomagnesemia, hypothyroidism, and impaired renal function all increase toxicity risk even at lower serum levels. 1

Sex-related differences: Post-hoc analysis suggested women may have increased mortality risk with digoxin, particularly at higher serum concentrations, though this remains controversial and may reflect prescription bias in sicker patients. 1

Common Clinical Pitfalls

• Withdrawing digoxin abruptly: Clinical worsening after digoxin withdrawal has been demonstrated; if discontinuing, do so cautiously. 1

• Using digoxin as first-line therapy: GDMT should be optimized first; digoxin is reserved for persistent symptoms despite optimal neurohormonal blockade. 1

• Targeting traditional "therapeutic" levels: The old therapeutic range of 0.8-2.0 ng/mL is associated with increased mortality; target 0.5-0.9 ng/mL instead. 1

• Assuming benefit in HF with preserved ejection fraction (HFpEF): Evidence is limited to HFrEF populations. 1

Bottom Line for Clinical Practice

Digoxin remains a reasonable option—not a contraindication—for carefully selected HFrEF patients who remain symptomatic despite comprehensive GDMT optimization. 1 Its primary value is reducing HF hospitalizations, not improving survival. 1, 2 The key is using low doses targeting serum concentrations of 0.5-0.9 ng/mL, monitoring for drug interactions and electrolyte abnormalities, and recognizing that newer agents (SGLT2 inhibitors, ARNI, vericiguat) have supplanted digoxin as preferred add-on therapies in most contemporary practice. 1