Low dose digoxin may help people with heart failure avoid hospitalization and reduce the risk of death, according to three studies led by UMCG cardiologists Dirk Jan van Veldhuisen, Kevin Damman, and Peter van der Meer. The researchers said the new data could ultimately inform heart failure treatment guidelines and widen access to this inexpensive therapy.
Low dose digoxin and the ‘Fantastic Four’
Heart failure is a growing public health challenge. An estimated 500,000 people in the Netherlands live with the condition, a number expected to rise. When the heart cannot pump effectively, patients can experience shortness of breath, fatigue, and frequent hospital visits.
Current standard care depends on a combination of four medications known colloquially as the Fantastic Four. Cardiologists have long explored whether adding digoxin could deliver extra benefit as a fifth option.
Three UMCG studies now bolster that case. Findings were published in journals including Nature Medicine and the Journal of the American Medical Association, and presented at the ESC Heart Failure Congress in Barcelona.
Heart failure hospitalizations fell by 25%
One randomized study enrolled 1,000 heart failure patients treated at 43 centers across the Netherlands. Half received a low dose of digoxin on top of usual care for an average of three years, while the other half were given a placebo.
In the digoxin group, deaths from cardiovascular causes and worsening heart failure declined by 19 percent, though this single outcome did not reach statistical significance.
Researchers then conducted a meta-analysis combining these results with two earlier trials, yielding a larger pooled population. With the added data, they reported a meaningful and statistically significant benefit for digoxin even when patients were already on the four standard therapies.
The most pronounced effect was a reduction in heart failure admissions, which fell by an average of 25 percent. The low dose regimen was also deemed safe and relatively straightforward to use.
Problems increased after stopping treatment
A third analysis followed about 600 of the original 1,000 participants who had been assigned either digoxin or placebo. People who had been taking digoxin and then stopped experienced significantly more issues in the first six weeks than those who had never received it. Among 288 patients, 14 were hospitalized or died.
The team cautioned that this observation does not directly prove efficacy, but they called the magnitude and timing of the effect striking.
A heart failure drug for under ten cents a day
The investigators believe the combined results could eventually prompt updates to heart failure guidelines, potentially expanding the use of digoxin.
Cost is a key consideration. Digoxin has been used for centuries and costs less than ten cents per day, whereas many newer heart failure drugs cost several euros daily.
Why dose matters for low dose digoxin
Digoxin, or digitalis, is among the oldest and least expensive heart failure treatments. At a low dose, it mainly blunts harmful compensatory responses that arise when the heart is failing, for example by suppressing circulating stress hormones such as adrenaline, which can benefit cardiac function.
Higher doses, once common, increase the strength of heart muscle contractions. That effect proved less helpful over time, since reducing strain on a weakened heart is often preferable to forcing it to work harder.
With the advent of multiple effective therapies over the past 25 to 30 years, digoxin use has declined, and only about 15 percent of patients now receive it. Earlier research suggested that lower doses were associated with better outcomes than higher doses, but until the UMCG program, randomized prospective evidence had been lacking.
Funding enabled the research
Studies of older, low-cost medicines can be challenging to finance, even when they may improve outcomes and reduce spending. Hartstichting provided 3 million euros for this work in collaboration with ZonMw under the Good Use of Medicines program.
Earlier research suggested that lower doses were associated with better outcomes than higher doses, but until the UMCG program, randomized prospective evidence had been lacking. Similar questions about optimizing older and newer treatments are also being explored in areas such as how Ozempic and the brain: clues to a hidden craving center may influence future prescribing.