January 10, 2026Heart Failure Reviews0 citations
The DIGIT-HF trial and the Mihai Gheorghiade legacy: time to reconsider cardiac glycosides as effective therapy in HFrEF
Key Result
DIGIT-HF trial demonstrated that digitoxin is safe and potentially effective for improving outcomes in patients with HFrEF receiving contemporary guideline-directed medical therapy.
Key Points
- The aim is to evaluate the efficacy and safety of digitoxin in patients with heart failure and reduced ejection fraction post-guideline therapy.
- Discussion of the DIGIT-HF trial findings
- Comparison of digitoxin with digoxin
- Evaluation of pharmacokinetics in the context of renal function
- Review of historical context regarding cardiac glycosides
- Digitoxin showed a favorable safety profile compared to older therapies
- The trial found potential improvements in symptoms and reduced rehospitalizations
- Efficacy of digitoxin evaluated in the context of contemporary guideline-directed medical therapy
Structured PICO
Does digitoxin improve outcomes in contemporary patients with HFrEF?
P
Population
Patients with heart failure with reduced ejection fraction (HFrEF)
I
Intervention
Digitoxin
This article discusses the DIGIT-HF trial and the potential role of digitoxin, a cardiac glycoside with hepatic clearance, in contemporary HFrEF management.
Main Result
Absolute Event Rate: 0% vs 0%
Abstract
Cardiac glycosides have been used for more than two centuries in patients with heart failure with reduced ejection fraction (HFrEF), but their use has steadily declined in recent decades, largely due to safety concerns raised by observational studies and the availability of outcome-modifying therapies with more favorable safety profiles. Evidence from earlier randomized trials suggested that digoxin improves symptoms and reduces heart-failure hospitalizations without affecting survival, but these studies were conducted before the widespread adoption of contemporary guideline-directed medical therapy (GDMT). Digitoxin is a cardiac glycoside that differs from digoxin through its hepatic clearance and more stable pharmacokinetics, diminishing the impact of renal dysfunction and serum concentration fluctuations, thereby improving safety and facilitating long-term use in routine care. Here, we critically discuss in the context of available evidence the findings of the recently published DIGIT-HF (Digitoxin to Improve Outcomes in Patients with Advanced Chronic Heart Failure) trial, which for the first time evaluated the efficacy and safety of digitoxin in contemporary patients with HFrEF.