2025Heart failure1240 patients

DIGIT-HF

Therapy group: Digitalis glycosides · Therapy: Digitoxin vs placebo

In heart failure with reduced ejection fraction on contemporary therapy, digitoxin reduced the composite of all-cause death or heart failure hospitalization.

Published in N Engl J Med (2025)

Question: Does adding digitoxin to guideline-directed medical therapy reduce death or hospital admission for worsening heart failure in patients with reduced ejection fraction?
Design: International, randomized 1:1, double-blind, placebo-controlled trial with 1240 patients randomized (1212 in the modified intention-to-treat population) and a median follow-up of 36 months.
Population: Patients with chronic heart failure with LVEF ≤40% and NYHA class III-IV, or LVEF ≤30% and NYHA class II, receiving guideline-directed medical therapy.
Intervention: Digitoxin at a starting dose of 0.07 mg once daily, added to usual therapy.
Control: Matching placebo added to guideline-directed medical therapy.
Primary outcome: Composite of death from any cause or hospital admission for worsening heart failure, whichever occurred first.
Results: The primary outcome occurred in 242 patients (39.5%) with digitoxin and 264 (44.1%) with placebo (HR 0.82; 95% CI 0.69 to 0.98; P = 0.03). All-cause death was 27.2% vs 29.5% (HR 0.86; 95% CI 0.69 to 1.07).
Safety: At least one serious adverse event occurred in 29 patients (4.7%) with digitoxin and 17 (2.8%) with placebo.
Conclusion: Digitoxin lowered the combined risk of death or hospital admission for worsening heart failure versus placebo in patients with reduced ejection fraction on guideline-directed therapy.
Why it matters: It renews interest in cardiac glycosides as add-on therapy in heart failure with reduced ejection fraction, supported by a placebo-controlled trial on top of current background treatment.

Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.

Generated on October 18, 2026

Sources

Original publication on PubMed (PMID 40879434) ↗Digitoxin in Patients with Heart Failure and Reduced Ejection Fraction.
Journal article (DOI) ↗

Videos explaining it

Hot Line 1 – DIGIT-HF: Digitoxin in Patients with Heart Failure and Reduced Ejection Fraction

ESC · European Society of Cardiology ↗2:07Video page

Source: European Society of Cardiology · YouTube
Date: 29 Aug 2025
Audio: English
Subtitles: MultilingualYouTube
Audio transl.: Unconfirmed · check ⚙YouTube

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Podcasts explaining it

Special episode (ESC 2025: REBOOT-CNIC, BETAMI-DANBLOCK, DIGIT-HF)
Cardiology Trials · Cardiology Trials ↗41 minEpisode page
Source
Cardiology Trials · Apple Podcasts
Date
9 Sept 2025
Audio
English
Translation
TextGoogle Chrome
Audio transl.
None
DIGIT-HF: digitoxin in the treatment of symptomatic HFrEF.
SBC · SBC Podcasts ↗6 minEpisode page
Source
SBC · SoundCloud
Date
29 Aug 2025
Audio
Portuguese
Translation
TextGoogle Chrome
Audio transl.
None

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