A low dose of digoxin ensures that people with heart failure are hospitalized and die less frequently. This emerges from three studies led by UMCG cardiologists Dirk Jan van Veldhuisen, Kevin Damman, and Peter van der Meer. They expect that these latest insights will lead to changes in heart failure guidelines in the future, allowing many more patients to access this inexpensive medication.
Heart failure is a major health concern. It is estimated that more than 500,000 people in the Netherlands live with heart failure. This number is expected to rise further in the coming years. The heart of a heart failure patient is less able to pump blood effectively, often resulting in severe shortness of breath, fatigue, and repeated hospital admissions.
Currently, the standard treatment for heart failure consists of a combination of four different medications, also known as the 'Fantastic Four.' For years, cardiologists have studied whether digoxin could be a valuable addition as a fifth medication. The three UMCG studies have now shown that this is the case. Their research was published today in, among others, Nature Medicine and the Journal of the American Medical Association (JAMA) and presented at the ESC Heart Failure Congress in Barcelona.
25% fewer hospital admissions
The researchers conducted a study among 1,000 Dutch heart failure patients from 43 different centers. One half of the patients received a low dose of digoxin in addition to their treatment for an average of three years, the other half received a placebo. Digoxin substantially reduced deaths from cardiovascular disease and heart failure worsening (by 19%). However, this effect was not statistically significant. Thanks to a meta-analysis with two earlier studies—combining a much larger patient population—the researchers were able to establish that digoxin does have an important and statistically significant added value. This was the case even when it was given in addition to the four standard medications for heart failure. The effect is mainly reflected as an average reduction of 25% in the number of hospital admissions for heart failure. A low dose of digoxin also proved to be safe and easy to use.
More problems when stopping digoxin
In a third study, the researchers followed approximately 600 of the 1,000 patients who had received either digoxin or placebo. It turned out that patients who had received digoxin and subsequently had to stop taking it experienced significantly more problems in the first six weeks than patients who had never received the medication. Out of 288 patients, 14 were hospitalized or died. Although this does not directly prove that the medicine works, the effect was found to be impressive and surprising, according to the researchers.
Ten cents a day
The researchers expect that the results of the three studies will change future heart failure guidelines, enabling many more patients to use this inexpensive medicine. This is particularly notable because digoxin has existed for centuries and is very affordable compared to many modern heart failure medications. Digoxin costs less than ten cents a day, whereas many new heart failure drugs cost several euros per day.
Why digoxin and why a low dose?
Digoxin (digitalis) is the oldest and cheapest medicine for the treatment of heart failure. A low dose of digoxin mainly reduces various adverse compensatory mechanisms in heart failure. For example, it inhibits stress hormones (such as adrenaline) in the blood, which is a beneficial effect. In the past, higher doses of digoxin were often used. This caused heart muscle cells to contract more, which turned out not to be beneficial: it is better to relieve a weakened heart muscle.
Over the last 25 to 30 years, several effective heart failure medicines have become available. As a result, the use of digoxin has gradually decreased: about 15 percent of all heart failure patients are prescribed it. Previous studies already showed that patients treated with low doses of digoxin fared much better than those receiving high doses. Until this new UMCG research, however, there had been no randomized, prospective studies actually investigating and confirming this.
Research made possible by Hartstichting
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.
Link to the publication in Nature: Low-dose digoxin in patients with heart failure with reduced or mildly reduced ejection fraction: a randomized controlled trial | Nature Medicine .
