A low dose of digoxin can 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. Researchers believe the new findings could eventually influence heart failure treatment guidelines and make this inexpensive drug available to many more patients.
Heart failure is a serious and growing health problem. It is estimated that more than 500,000 people in the Netherlands suffer from this condition and that number is expected to increase in the coming years. In people with heart failure, the heart cannot pump blood as effectively as it should. This can lead to severe shortness of breath, fatigue, and repeated trips to the hospital.
Digoxin could join the ‘Fantastic Four’
Standard care for heart failure currently relies on a combination of four medications, commonly known as the “Fantastic Four.” Cardiologists have long investigated whether digoxin could provide additional benefits as a fifth treatment.
Three UMCG studies now provide evidence supporting that possibility. The findings were published in publications including Nature medicine and the Journal of the American Medical Association (JAMA) and were also presented at the ESC Heart Failure Congress in Barcelona.
Hospitalizations for heart failure fell 25%
One of the studies included 1,000 people with heart failure who were treated at 43 centers in the Netherlands. Half received a low dose of digoxin in addition to their usual treatment for an average of three years, while the other half received a placebo.
Among those taking digoxin, deaths from cardiovascular disease and worsening heart failure were reduced (by 19%). However, this individual result did not reach statistical significance.
The researchers then combined the findings with data from two previous studies in a meta-analysis, creating a much larger group of patients. With the additional data, they found that digoxin produced a significant and statistically significant benefit, even when patients were already taking the four standard heart failure medications.
The clearest benefit was a reduction in hospital admissions for heart failure, which fell by an average of 25%. Low-dose digoxin was also found to be safe and relatively easy to use.
Problems increased after stopping digoxin
A third study followed approximately 600 of the original 1,000 participants who had been assigned digoxin or placebo.
Researchers found that people who had been taking digoxin and then had to stop experienced significantly more problems during the first six weeks compared to people who had never taken the drug. Among 288 patients, 14 were hospitalized or died.
According to the researchers, this finding does not directly prove that digoxin is effective. Still, they found the size and timing of the effect to be impressive and surprising.
A heart failure drug that costs less than ten cents a day
The researchers believe that the results of the three studies could eventually lead to changes in heart failure guidelines, which could allow many more patients to receive digoxin.
Its low price makes the finds especially notable. Digoxin has been used in medicine for centuries and costs less than ten cents a day. By comparison, many newer heart failure medications cost several euros a day.
Why a low dose of digoxin is important
Digoxin (digital) is the oldest and least expensive medication used to treat heart failure. At low doses, the drug works primarily by reducing several harmful compensatory responses that occur when the heart is in trouble. For example, digoxin suppresses stress hormones (such as adrenaline) in the blood, which can benefit the heart.
In the past, higher doses of digoxin were commonly prescribed. Those doses caused heart muscle cells to contract more forcefully, but that effect ultimately proved less useful. For a weakened heart muscle, it is preferable to reduce tension than to force it to work harder.
Over the past 25 to 30 years, several new and effective treatments for heart failure have become available. As a result, the use of digoxin has steadily declined and currently only about 15 percent of heart failure patients receive it.
Previous research had already suggested that patients who received low doses of digoxin fared considerably better than those who received higher doses. However, until the new UMCG research, prospective randomized studies had not directly investigated or confirmed this effect.
Funding Made Digoxin Studies Possible
Research involving older, cheaper drugs can be difficult to fund, even when those drugs have the potential to improve patient care while reducing costs.
For this reason, Hartstichting contributed 3 million euros for this research through its collaboration with ZonMw within the framework of the Good Use of Medicines program.