Digoxin, a cardiac glycoside, has shown promise in treating rheumatic heart disease (RHD), a condition affecting millions worldwide, particularly in low- and middle-income countries. The DIG-RHD trial, conducted in India, randomized 880 patients with RHD to digoxin or placebo, revealing a 4.1% absolute reduction in the primary endpoint of all-cause mortality or new/worsening heart failure (HF) over 2.1 years. This reduction was primarily driven by improved HF outcomes, with no significant difference in all-cause mortality. The study's findings are particularly relevant to developing nations, where RHD is prevalent and often undermanaged. The low cost of the trial ($600,000) and the drug's affordability make it a viable treatment option for resource-constrained settings. The neutral effect on all-cause mortality aligns with previous studies in heart failure with reduced ejection fraction (HFrEF). The trial also noted a treatment effect in patients with atrial fibrillation (AF) at baseline, suggesting digoxin's potential in managing RHD, especially in those with AF. While digoxin toxicity was suspected in a small number of patients, it did not lead to hospitalizations or death. The study's pragmatic nature and positive results make digoxin a promising adjunctive therapy for RHD, offering symptom relief and reduced HF hospitalizations without a significant impact on mortality. This is particularly encouraging given the lack of proven medical therapies for RHD, which often leads to HF and premature deaths. The World Health Organization's recognition of digoxin as an essential medicine further supports its potential role in global RHD management.
