An old and inexpensive heart medicine may have a new role in modern heart failure care.
Three studies led by researchers at the University Medical Center Groningen, or UMCG, suggest that low-dose digoxin may reduce hospital stays and could improve outcomes for people already receiving standard treatment.
The work was led by UMCG cardiologists Dirk Jan van Veldhuisen, Kevin Damman, and Peter van der Meer. Findings from the research were published in major medical journals including Nature Medicine and JAMA and were also presented at the ESC Heart Failure Congress in Barcelona.
Heart failure does not mean that the heart has completely stopped working. Instead, it means the heart is unable to pump enough blood to meet the body’s needs, or can do so only under increased pressure.
This can cause shortness of breath, tiredness, swelling in the legs, and difficulty exercising. People with more advanced disease may repeatedly need hospital treatment when fluid builds up or their symptoms suddenly become worse.
Heart failure is common and becomes more likely with age. More than 500,000 people in the Netherlands are estimated to have the condition, and growing older populations mean the number could rise further.
Treatment has improved greatly during the past few decades. Many patients with certain forms of heart failure are now treated with a group of four types of medicines that work in different ways to protect the heart and reduce the chance of hospitalization or death.
These treatments are sometimes informally called the “Fantastic Four.” Researchers have been asking whether digoxin, a medicine that has existed for centuries, could provide additional protection when added to modern therapy.
One of the new UMCG studies involved about 1,000 people with heart failure treated at 43 medical centers across the Netherlands. Participants continued their usual heart failure treatment and were randomly assigned to receive either a low dose of digoxin or a placebo.
They were followed for an average of about three years. Cardiovascular deaths and worsening heart failure were 19% lower in the digoxin group, although this individual result did not meet the statistical standard researchers use to rule out chance with sufficient confidence.
That distinction is important. A numerical difference can look encouraging, but researchers generally require stronger statistical evidence before concluding that a treatment has produced a reliable benefit.
The scientists therefore also combined their results with information from two earlier studies. This larger analysis provided more evidence about how low-dose digoxin performed across a broader group of patients.
The clearest finding involved hospitalization. When the studies were considered together, digoxin was associated with about a 25% reduction in hospital admissions caused by worsening heart failure.
This could be important for patients because heart failure hospitalizations are physically difficult and often signal worsening disease. They also place a large burden on hospitals and healthcare systems.
The researchers reported that low-dose digoxin was generally safe and relatively simple to use. Dose matters because digoxin has a long history of being prescribed at higher levels, which can increase the risk of harmful effects.
Digoxin comes from digitalis compounds originally associated with the foxglove plant. It affects the heart and the body’s nervous and hormonal responses, and for many years it was one of the main medicines available for heart failure.
At higher doses, digoxin can make the heart contract more strongly. Modern researchers are more interested in lower doses, which may reduce harmful stress responses in the body without putting unnecessary extra strain on an already weakened heart.
A third UMCG study offered another interesting clue. Researchers followed about 600 people from the original trial after the treatment period and examined what happened when participants stopped their assigned medicine.
People who had been taking digoxin and then stopped appeared to experience more problems during the first six weeks than people who had previously received placebo. Among 288 patients in the relevant digoxin group, 14 were hospitalized or died.
The researchers cautioned that this withdrawal finding does not by itself prove that digoxin was responsible for protecting patients. Still, the timing and size of the difference were striking enough to support further investigation.
Another reason the findings attract attention is cost. Digoxin can cost less than ten cents a day, while some newer medicines may cost several euros per day.
Low price does not automatically make a medicine better, but an effective inexpensive treatment can have enormous value. This is especially true in health systems with limited resources and in countries where access to newer heart medicines remains difficult.
Research on old generic medicines can be challenging because companies have little financial incentive to pay for expensive trials when the drug itself produces little profit. The Dutch Heart Foundation provided 3 million euros for this work through a collaboration with ZonMw’s Good Use of Medicines program.
In reviewing the evidence, the roughly 25% reduction in heart failure hospitalization is the most convincing and clinically meaningful result. The randomized design of the main study is also a major strength because it reduces many of the biases that can affect observational research.
However, the 19% reduction in cardiovascular death and worsening heart failure in the main trial was not statistically significant on its own. The stronger conclusion came after combining studies, so future research and detailed review of which patients benefit most will remain important.
The findings therefore do not mean every person with heart failure should begin taking digoxin. Digoxin can become harmful when blood levels are too high, and kidney function, other medicines, heart rhythm, and individual health can affect how safely it can be used.
Overall, the studies give a very old drug a surprisingly modern second look.
If further evidence confirms that carefully dosed digoxin safely reduces hospitalizations on top of today’s standard therapy, it could become a low-cost additional option for selected people with heart failure.
