New research indicates that low-dose digoxin may provide significant benefits for heart failure patients.
A low dose of digoxin may help people with heart failure avoid hospitalization and reduce their risk of death, according to three studies led by UMCG cardiologists Dirk Jan van Veldhuisen, Kevin Damman, and Peter van der Meer. The researchers believe the findings could eventually influence heart failure treatment guidelines and expand access to this low-cost medication.
Heart failure remains a major health problem. More than 500,000 people in the Netherlands are believed to be living with the condition, and that number is expected to keep growing. In heart failure, the heart cannot pump blood efficiently enough to meet the body’s needs, often causing severe shortness of breath, fatigue, and frequent hospital stays.
Investigating a Fifth Heart Failure Drug
Standard heart failure treatment currently relies on four medications commonly known as the “Fantastic Four.” Researchers have long explored whether digoxin could serve as a useful fifth therapy. The new UMCG studies suggest it can.
The findings were published in journals including Nature Medicine and the Journal of the American Medical Association (JAMA) and were also presented at the ESC Heart Failure Congress in Barcelona.
In one study, researchers tracked 1,000 heart failure patients from 43 medical centers across the Netherlands. Half received a low dose of digoxin alongside their regular treatment for an average of three years, while the rest received a placebo.
Patients taking digoxin showed a 19% reduction in deaths linked to cardiovascular disease and worsening heart failure. However, the result did not reach statistical significance.
Stronger Evidence Through Combined Analysis
The researchers then combined their results with data from two earlier studies in a larger meta-analysis involving many more patients. That broader analysis showed that digoxin provided a statistically significant benefit, even when added to the four standard heart failure medications.
The clearest effect was a roughly 25% reduction in hospital admissions related to heart failure. Researchers also found that low-dose digoxin was safe and simple to use.
A third study followed about 600 of the original participants who had received either digoxin or a placebo. Patients who stopped taking digoxin experienced significantly more complications during the first six weeks after discontinuing the drug compared with patients who had never taken it.
Among 288 patients who stopped treatment, 14 were hospitalized or died. Although the findings do not directly prove the medication’s effectiveness, researchers described the results as impressive and unexpected.
An Old Drug With Renewed Interest
The researchers say the combined findings could shape future heart failure guidelines and allow more patients to receive this inexpensive treatment.
Digoxin has been used for centuries and costs far less than many newer heart failure medications. The drug costs less than ten cents per day, while many modern heart failure treatments cost several euros daily.
Digoxin (digitalis) is the oldest and least expensive medication used to treat heart failure. At low doses, it mainly works by reducing harmful biological responses linked to heart failure. For example, it lowers levels of stress hormones (such as adrenaline) in the bloodstream, which may help reduce strain on the heart.
In the past, doctors often prescribed much higher doses of digoxin. Those doses increased the strength of heart muscle contractions, but researchers later found that effect was not beneficial. Relieving stress on a weakened heart appears to be more effective than forcing it to work harder.
Why Lower Doses Matter
Over the past 25 to 30 years, several highly effective heart failure treatments have become available. As a result, digoxin use has steadily declined, and only about 15% of heart failure patients currently receive the drug.
Earlier studies had already suggested that patients taking low doses of digoxin had better outcomes than those receiving higher doses. However, before this new UMCG research, no randomized prospective studies had directly tested and confirmed those benefits.
Reference: “Low-dose digoxin in patients with heart failure with reduced or mildly reduced ejection fraction: a randomized controlled trial” by D. J. van Veldhuisen, M. Rienstra, A. Mosterd, M. Alings, A. A. Voors, K. Damman, A. D. I. van Asselt, M. L. Bouvy, J. Schaap, E. E. van der Wall, H. J. G. M. Crijns, D. J. Touw, P. A. M. Hoogslag, J. E. C. van de Swaluw, R. J. Schuurman, A. van der Sluis, O. Bondarenko, T. J. Römer, T. Oosterhof, G. L. Bartels, S. Koudstaal, P. A. Dijkmans, G. C. M. Linssen, I. Aksoy, H. G. R. Dorman, A. Schut, M. E. W. Hemels, R. G. Tieleman, D. J. A. Lok, I. C. D. Westendorp, M. A. T. Vijver, G. H. D. Voordes, A. H. de Vos, E. L. Maas-Soer, D. Postmus, G. Lunter, J. G. P. Tijssen and P. van der Meer, 10 May 2026, Nature Medicine.
DOI: 10.1038/s41591-026-04406-6
“Efficacy and Safety of Digitalis Glycosides in Heart Failure: A Meta-Analysis” by Kevin Damman, Dirk J. van Veldhuisen, Johann Bauersachs, Michiel Rienstra, Arend Mosterd, Adriaan A. Voors, Geert H. D. Voordes, Udo Bavendiek and Peter van der Meer, 10 May 2026, JAMA.
DOI: 10.1001/jama.2026.7886
It is difficult to obtain funding for research into this kind of medication, even though they can contribute to better and more affordable patient care. Hartstichting therefore invested 3 million euros in this research as part of its collaboration with ZonMw within the Good Use of Medicines program.
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