AIIMS-led trial finds low-cost drug digoxin may improve outcomes in rheumatic heart disease

A trial by AIIMS shows digoxin may reduce worsening heart failure in rheumatic heart disease patients, offering a low-cost treatment option.

A major clinical trial, led by researchers from All India Institute of Medical Sciences (AIIMS), has found that the low-cost heart drug digoxin may help reduce worsening heart failure in patients suffering from rheumatic heart disease (RHD), a condition that continues to affect millions in India.

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The findings come from the study, “Digoxin in Patients With Symptomatic Rheumatic Heart Disease: A Randomized Clinical Trial”, published in the Journal of the American Medical Association (JAMA), a peer-reviewed medical journal on May 10.

The study was led by cardiologist Ganesan Karthikeyan from AIIMS and Niveditha Devasenapathy from Translational Health Science and Technology Institute, and Arpita Ghosh from The George Institute for Global Health, along with researchers from multiple institutions across India and abroad.

Rheumatic heart disease is caused by damage to heart valves following untreated or poorly treated rheumatic fever, which develops after certain bacterial throat infections. The disease remains a major public health burden in developing countries and often affects younger adults.

According to the study, RHD affects more than 40 million people globally and leads to nearly 320,000 deaths every year. Heart failure is the leading cause of death among these patients.

Researchers said that despite the widespread use of digoxin for decades, there has been limited evidence from randomised trials on whether the drug improves outcomes in patients with rheumatic heart disease. Digoxin is a low-cost medicine commonly used to control heart rate and improve heart function.

The cost of digoxin in the private market varies significantly depending on the brand, manufacturer, and whether it is a tablet or injection. The drug in India is priced under ₹20 per 10-tablet strip of .25 mg.

For the study, the trial enrolled 1,769 adults with symptomatic rheumatic heart disease across 12 tertiary care hospitals in in the country between February 2022 and August 2024.

Participants either had heart failure, atrial fibrillation or were already taking digoxin before entering the study. Patients were randomly assigned to receive either oral digoxin or a matching placebo in addition to standard treatment and were followed for a median period of around two years.

The researchers found that patients receiving digoxin had a lower risk of the combined outcome of death or new-onset,worsening heart failure compared with those receiving placebo. “In patients with symptomatic rheumatic heart disease, digoxin reduced the risk of a composite of all-cause death or new-onset or worsening heart failure, with little risk of toxicity,” reads the study.

The study further added that the benefit was mainly driven by a reduction in worsening heart failure episodes. “New-onset or worsening heart failure occurred in 25.8 per cent of patients receiving digoxin, compared with 29.2 per cent in the placebo arm. However, the study did not find a significant difference in overall mortality between the two groups,” added the study.

Researchers in their study noted that the findings are particularly important in low- and middle-income countries where access to hospital care is often limited and many patients are managed on an outpatient basis.

The study also reported a low incidence of suspected digoxin toxicity. A total of 24 patients had suspected toxicity, including 17 in the digoxin group and seven in the placebo group. Only 10 patients receiving digoxin permanently discontinued the medicine because of suspected toxicity. Researchers said the relatively young age of participants and low levels of kidney disease may have contributed to the lower risk of side effects.

The authors said the findings suggest that digoxin could offer a simple and affordable option for reducing heart failure worsening in rheumatic heart disease patients. “Digoxin thus appears to be a safe and inexpensive treatment for reducing heart failure worsening in patients with symptomatic RHD.”