Digoxin Trial Shows Significant Benefit for Rheumatic Heart Disease Patients
A recent study presented at the American College of Cardiology's Annual Scientific Session (ACC.26) has revealed promising results for patients suffering from rheumatic heart disease (RHD).
Patients with rheumatic heart disease (RHD) who received the drug digoxin had an 18% lower risk of death or new-onset or worsening heart failure over a two-year period compared to those given a placebo. This randomized trial suggests that digoxin can significantly benefit patients with RHD.
Understanding Rheumatic Heart Disease
Rheumatic heart disease is a severe condition resulting from heart valve damage. This damage is typically caused by rheumatic fever, which itself is triggered by an abnormal immune response to strep throat, often experienced in childhood.
The disease poses a significant global health challenge, affecting an estimated 55 million people worldwide and leading to approximately 360,000 deaths each year. RHD disproportionately impacts low- and middle-income countries, where essential treatments like surgical valve repair are often inaccessible.
Trial Design and Participants
The study, which ran from 2022 to 2025, enrolled 1,769 patients receiving treatment for symptomatic RHD across 12 sites in India. Participants were primarily young adults, with an average age of 46 years, and 72% of them were women.
The trial was designed as a randomized study, with half of the participants prescribed digoxin and the other half receiving a placebo. The treating clinician was responsible for determining the appropriate dosing for each patient.
Key Findings on Efficacy
After a median follow-up of 2.1 years, the digoxin group demonstrated an 18% lower rate of the primary endpoint. This crucial endpoint combined death from any cause and new-onset or worsening heart failure.
Detailed analysis indicated that this benefit was primarily driven by a significant reduction in new-onset or worsening heart failure, with no notable difference in overall mortality between the groups. A secondary endpoint, which combined death related to heart failure and new-onset or worsening heart failure, also showed an 18% reduction.
Safety Profile and Broader Implications
Digoxin is known to have potential side effects, including gastrointestinal issues, vision changes, and irregular heartbeat. However, the trial reported a remarkably low rate of toxicities, with only 1% of participants experiencing such effects, most of which were minor. Crucially, no toxicity-related hospitalizations or deaths occurred during the study.
Researchers emphasized that these findings offer significant reassurance regarding digoxin's general safety and effectiveness for RHD treatment. The outcomes were consistent across different demographics, showing no variation by sex or body mass index. While not conclusively proven by this study design, patients with atrial fibrillation appeared to experience an even greater benefit from digoxin.
Ganesan Karthikeyan, MD, senior author and professor of cardiology, stated, "The trial's publication may increase confidence in using digoxin, as it is the first drug to demonstrate benefit in RHD patients through a randomized trial."
Funded by the Indian Council of Medical Research, the study's findings are considered highly generalizable to patients in many developing low- and middle-income countries, offering a new, accessible therapeutic option.