Digoxin may Reduce Mortality and Heart Failure Risk in Symptomatic Rheumatic Heart Disease, Suggests Study
India: A new study has found that among patients with symptomatic rheumatic heart disease, digoxin was associated with a lower risk of the combined outcome of all-cause mortality and new-onset or worsening heart failure, while showing minimal toxicity risk. The findings were presented alongside the European Society of Cardiology Heart Failure 2026 Congress and published in JAMA.
The study was led by Ganesan Karthikeyan from the All India Institute of Medical Sciences and colleagues. Since heart failure is a major cause of death in rheumatic heart disease (RHD), the researchers evaluated the efficacy and safety of digoxin in this population through a multicenter, randomized, placebo-controlled trial conducted across 12 tertiary care hospitals in India.
The trial enrolled patients with RHD who had heart failure, atrial fibrillation, or were already on digoxin therapy between February 2022 and August 2024. Participants were randomly assigned to receive either oral digoxin (0.125–0.25 mg daily) or a placebo along with standard care, with a median follow-up of 2.1 years.
The primary endpoint was a composite of all-cause death or new-onset/worsening heart failure. Secondary outcomes included all-cause mortality, worsening heart failure, and heart failure–related death. Of the 1769 enrolled patients, 1759 were included in the final analysis. The mean age was 46 years, and 72% of participants were women.
The trial findings were as follows:
- Most participants had mixed valvular disease involving multiple valves, and 85% had moderate to severe mitral stenosis.
- Atrial fibrillation was present in 70% of patients, while most participants were classified as New York Heart Association class II to IV.
- The primary composite outcome of all-cause death or new-onset/worsening heart failure occurred in 31.4% of patients receiving digoxin compared with 35.5% in the placebo group.
- Digoxin therapy was associated with an 18% lower risk of the primary composite outcome compared with placebo.
- Patients receiving digoxin experienced fewer episodes of new-onset or worsening heart failure.
- Most worsening heart failure events were managed with oral or intravenous diuretics without hospitalization.
- All-cause mortality rates were similar between the two groups, occurring in 10% of the digoxin group and 10.4% of the placebo group.
- Permanent discontinuation due to suspected digoxin toxicity was uncommon and occurred in only 1.1% of patients receiving digoxin.
The researchers acknowledged certain limitations, including the fact that all participants were recruited from India, which may limit generalizability to other rheumatic heart disease–endemic regions. They also cautioned that the favorable safety profile observed in this relatively young population with preserved kidney function may not apply to older patients or those with renal impairment.
Overall, the authors concluded that digoxin may offer a safe, low-cost option to reduce worsening heart failure events in patients with symptomatic rheumatic heart disease.
Reference:
Karthikeyan G, Devasenapathy N, Ghosh A, et al. Digoxin in Patients With Symptomatic Rheumatic Heart Disease: A Randomized Clinical Trial. JAMA. Published online May 10, 2026. doi:10.1001/jama.2026.7335
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