Digoxin lowered the risk of death or new-onset or worsening heart failure (HF) compared with placebo in patients with rheumatic heart disease (RHD), according to results from the Dig-RHD trial presented during a Late-Breaking Clinical Trial session at ACC.26 in New Orleans.

The double-blind Dig-RHD trial, conducted across 12 sites in India from 2022-2025, randomized 1,769 treated patients with symptomatic RHD (mean age, 46 years; 72% women) 1:1 to either placebo or digoxin, with dosing and administration strategy left to clinician discretion. The all-comer enrollment excluded only patients in whom digoxin would not normally be given; 34% were already taking the drug at baseline.

Results at a median follow-up of 2.1 years showed that digoxin was associated with an 18% reduction in the composite primary endpoint of all-cause death or new or worsening HF, driven primarily by a reduction in new or worsening HF. There was no significant difference in mortality between the two groups.

The secondary composite endpoint of HF-related death and new or worsening HF was similarly reduced by 18%. Effects were consistent across sex and BMI with a possible greater benefit among patients with atrial fibrillation.

Toxicity was uncommon, occurring in just 1% of patients, and led to no related hospitalizations or deaths.

“Digoxin is used in about 30%-40% of [RHD] cases currently, but it’s based on the physician’s gut feeling and there’s always a concern that it will worsen things,” said Ganesan Karthikeyan, MD, the study’s senior author. “With the publication of this trial, I think people will be a little more confident about using digoxin. We have few other drugs to benefit these patients – and this is the first drug which has evidence of benefit from a randomized trial – so I think its use will increase.”

Although the trial was conducted only in India, researchers said that it should be generalizable to patients in many developing low- and middle-income countries since its pragmatic design and all-comer population reflects the patients who typically come to the hospital for RHD in such regions.

Clinical Topics: Valvular Heart Disease

Keywords: ACC Annual Scientific Session, ACC26, New Orleans, Heart Valve Diseases, Mortality, Rheumatic Heart Disease, Digoxin