A low dose of 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 believe the new findings could eventually influence heart failure treatment guidelines and make this inexpensive medication available to many more patients.
Heart failure is a serious and growing health problem. More than 500,000 people in the Netherlands are estimated to have the condition, and that number is expected to increase in the years ahead. 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 heart failure care 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.
Heart Failure Hospitalizations Fell by 25%
One of the studies included 1,000 people with heart failure who were treated at 43 centers across 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, that individual result did not reach statistical significance.
The researchers then combined the findings with data from two earlier studies in a meta-analysis, creating a much larger group of patients. With the additional data, they found that digoxin produced a meaningful 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 Digoxin Was Stopped
A third study followed approximately 600 of the original 1,000 participants who had been assigned either 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 with 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 considered the size and timing of the effect both impressive and surprising.
A Heart Failure Drug That Costs Less Than Ten Cents a Day
The researchers believe the results of the three studies could eventually lead to changes in heart failure guidelines, potentially allowing many more patients to receive digoxin.
Its low price makes the findings especially notable. Digoxin has been used in medicine for centuries and costs less than ten cents per day. By comparison, many newer heart failure medications cost several euros each day.
Why a Low Dose of Digoxin Matters
Digoxin (digitalis) is the oldest and least expensive medicine used to treat heart failure. At a low dose, the drug primarily works by reducing several harmful compensatory responses that occur when the heart is struggling. For example, digoxin suppresses stress hormones (such as adrenaline) in the blood, which can benefit the heart.
Higher doses of digoxin were commonly prescribed in the past. Those doses caused heart muscle cells to contract more strongly, but that effect ultimately proved less helpful. For a weakened heart muscle, reducing strain is preferable to forcing it to work harder.
During the past 25 to 30 years, several effective new treatments for heart failure have become available. As a result, digoxin use has steadily declined, and only about 15 percent of heart failure patients now receive it.
Earlier research had already suggested that patients given low doses of digoxin did considerably better than those receiving higher doses. Until the new UMCG research, however, randomized, prospective studies had not directly investigated and confirmed this effect.
Funding Made the Digoxin Studies Possible
Research involving older and inexpensive medications can be difficult to fund, even when those drugs have the potential to improve patient care while lowering costs.
Hartstichting therefore provided 3 million euros for this research through its collaboration with ZonMw as part of the Good Use of Medicines program.
