_{AUTHOR: Yazmin Sadik}

New findings from the DIGIT-HF trial indicate that adding low-dose digitoxin to guideline-directed medical therapy (GDMT) can reduce the risk of hospitalisation and all-cause mortality in patients with symptomatic heart failure with reduced ejection fraction (HFrEF).¹ 

The results were presented at the European Society of Cardiology (ESC) Congress 2025 and simultaneously published in The New England Journal of Medicine.

The international, double-blind, placebo-controlled DIGIT-HF trial randomised 1212 patients with HFrEF to receive either digitoxin or a matching placebo in addition to standard GDMT.¹ The patient cohort included individuals with chronic heart failure who had a left ventricular ejection fraction (LVEF) of 40% or less and were in New York Heart Association (NYHA) functional class III or IV, or had an LVEF of 30% or less and were in NYHA functional class II.

Participants in the intervention group received a starting dose of 0.07 mg of digitoxin once daily. The primary outcome was a composite of death from any cause or the first hospital admission for worsening heart failure.

Over a median follow-up of 36 months, a primary-outcome event occurred in 242 of 613 patients (39.5%) in the digitoxin group, compared with 264 of 599 patients (44.1%) in the placebo group (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.69 to 0.98; p=0.03).¹

For the individual components of the primary outcome, death from any cause occurred in 167 patients (27.2%) in the digitoxin group and 177 patients (29.5%) in the placebo group (HR, 0.86; 95% CI, 0.69 to 1.07). A first hospital admission for worsening heart failure was recorded for 172 patients (28.1%) in the digitoxin group and 182 patients (30.4%) in the placebo group (HR, 0.85; 95% CI, 0.69 to 1.05).

Regarding safety, at least one serious adverse event occurred in 29 patients (4.7%) in the digitoxin group and 17 patients (2.8%) in the placebo group.

The DIGIT-HF trial demonstrates that among patients with symptomatic HFrEF already receiving GDMT, treatment with low-dose digitoxin resulted in a lower combined risk of death from any cause or hospital admission for worsening heart failure compared with placebo. These findings suggest a potential role for this cardiac glycoside as an adjunctive therapy in this patient population.

This study was funded by the German Federal Ministry of Research, Technology, and Space, the Braukmann Wittenberg Heart Foundation, and the German Heart Foundation.

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References

1. Bavendiek U, Großhennig A, Schwab J, et al. Digitoxin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med 2025. https://doi.org/10.1056/NEJMoa2415471.

2. Wandersee K. New Data Support Digitoxin Comeback in Some Heart Failure Patients. Medscape. 30 August 2025. https://www.medscape.com/viewarticle/new-data-support-digitoxin-comeback-some-heart-failure-2025a1000myi.