Digoxin and Digitalis Glycosides for Heart Failure Management

New evidence presented on May 10, 2026, suggests that low-dose digitalis glycosides can serve as an effective additional treatment for patients managing heart failure with reduced or mildly reduced left ventricular ejection fraction, known as HF(m)rEF.

The findings were shared during a Late-Breaking Science session at Heart Failure 2026, the annual congress of the Heart Failure Association of the European Society of Cardiology held in Barcelona, Spain.

Researchers from the University Medical Center Groningen in the Netherlands evaluated the effects of digoxin and digitoxin, two types of digitalis glycosides. The totality of the evidence, including a new trial and a broad meta-analysis, supports the use of these medications in contemporary heart failure management.

The DECISION Trial and Meta-Analysis

The research centered on the DECISION trial, a double-blind study conducted across 43 sites in the Netherlands. The trial aimed to determine if low-dose digoxin provides positive cardiovascular outcomes for patients with HF(m)rEF who are already receiving guideline-recommended treatments.

In addition to the DECISION trial, researchers presented a meta-analysis encompassing three trials. This analysis included data from more than 9,000 patients suffering from heart failure and reduced ejection fraction.

The combined data indicates that these centuries-old medications remain relevant in modern medicine when administered at low doses.

Historical Context and the DIG Trial

The current findings address long-standing uncertainty regarding the value of digoxin in managing HF(m)rEF. This uncertainty largely stemmed from the 1997 DIG trial.

In that earlier study, digoxin was found to have a neutral effect on the primary endpoint of mortality. However, it did result in a 28% reduction in heart failure hospitalizations, which was a secondary endpoint.

Further analysis of the DIG trial revealed a critical distinction based on dosage: lower serum digoxin levels were linked to favorable effects, while higher levels were associated with a worsened prognosis.

Digoxin is the oldest drug in cardiovascular medicine, but there has been uncertainty about its value in HF(m)rEF management

Professor Dirk van Veldhuisen, Principal Investigator

Professor Dirk van Veldhuisen, the principal investigator, noted that the DECISION trial was specifically designed to investigate whether low-dose administration could optimize outcomes within the framework of current medical guidelines.

Clinical Implications for Heart Failure

The results suggest that digitalis glycosides are not replacements for contemporary therapies but rather supplemental tools. By utilizing low doses, clinicians may be able to reduce the frequency of worsening heart failure events.

The evidence presented in Barcelona emphasizes the importance of dosage precision, echoing the lessons learned from previous decades of cardiovascular research.