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Digitoxin in Patients with Heart Failure and Reduced Ejection Fraction
Udo Bavendiek1, Anika Großhennig2, Johannes Schwab3,4
1Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Insights
Digitoxin treatment significantly reduced the combined risk of death or heart failure hospitalization in patients with reduced ejection fraction. This study establishes digitoxin as a potential therapy for heart failure management.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- The efficacy of digitoxin, a cardiac glycoside, for treating heart failure with reduced ejection fraction (HFrEF) remains unproven.
- Guideline-directed medical therapy (GDMT) is standard for HFrEF, but additional treatments are needed.
Purpose of the Study:
- To evaluate the therapeutic efficacy of digitoxin compared to placebo in patients with HFrEF receiving GDMT.
- To assess the impact of digitoxin on mortality and heart failure hospitalizations.
Main Methods:
- An international, double-blind, placebo-controlled trial randomized 1240 patients with HFrEF to receive either digitoxin or placebo.
- Patients had left ventricular ejection fraction ≤40% (NYHA class III-IV) or ≤30% (NYHA class II).
- The primary outcome was a composite of all-cause death or hospital admission for worsening heart failure.
Main Results:
- In the modified intention-to-treat population (1212 patients), digitoxin reduced the primary composite outcome by 18% (hazard ratio, 0.82; P=0.03).
- Over a median of 36 months, digitoxin showed a trend towards lower all-cause mortality (HR, 0.86) and heart failure hospitalizations (HR, 0.85).
- Serious adverse events were more frequent in the digitoxin group (4.7% vs. 2.8%).
Conclusions:
- Digitoxin treatment significantly lowered the combined risk of death or heart failure hospitalization in HFrEF patients on GDMT.
- Digitoxin represents a potential therapeutic option for managing heart failure with reduced ejection fraction.
- Further research may explore optimal dosing and long-term safety profiles.
Background:
The therapeutic efficacy of the cardiac glycoside digitoxin in patients with heart failure and reduced ejection fraction is not established.
Methods:
In this international, double-blind, placebo-controlled trial, we randomly assigned patients with chronic heart failure who had a left ventricular ejection fraction of 40% or less and a New York Heart Association (NYHA) functional class of III or IV or a left ventricular ejection fraction of 30% or less and an NYHA functional class of II in a 1:1 ratio to receive digitoxin (at a starting dose of 0.07 mg once daily) or matching placebo in addition to guideline-directed medical therapy. The primary outcome was a composite of death from any cause or hospital admission for worsening heart failure, whichever occurred first.
Results:
Among 1240 patients who underwent randomization, 1212 fulfilled the criteria for inclusion in the modified intention-to-treat population: 613 patients in the digitoxin group and 599 in the placebo group. Over a median follow-up of 36 months, a primary-outcome event occurred in 242 patients (39.5%) in the digitoxin group and 264 (44.1%) in the placebo group (hazard ratio for death or first hospital admission for worsening heart failure, 0.82; 95% confidence interval [CI], 0.69 to 0.98; P = 0.03). Death from any cause occurred in 167 patients (27.2%) in the digitoxin group and 177 (29.5%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.69 to 1.07). A first hospital admission for worsening heart failure occurred in 172 patients (28.1%) in the digitoxin group and 182 (30.4%) in the placebo group (hazard ratio, 0.85; 95% CI, 0.69 to 1.05). At least one serious adverse event occurred in 29 patients (4.7%) in the digitoxin group and 17 (2.8%) in the placebo group.
Conclusions:
Treatment with digitoxin led to a lower combined risk of death from any cause or hospital admission for worsening heart failure than placebo among patients with heart failure and reduced ejection fraction who received guideline-directed medical therapy. (Funded by the German Federal Ministry of Research, Technology, and Space and others; DIGIT-HF EudraCT number, 2013-005326-38.).
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