Dig-RHD is the first RCT of digoxin in rheumatic heart disease. 1,769 patients across 12 Indian tertiary centers (mean age 46, 72% female, 70% AF, 90% NYHA II–IV, mostly with mixed valve lesions) were randomized to digoxin 0.125–0.25 mg/day or placebo and followed a median 2.1 years. The primary composite of all-cause death or new-onset/worsening HF occurred in 31.4% (digoxin) vs 35.5% (placebo) — HR 0.82; 95% CI 0.69–0.96. Practice-changing for the Global South where RHD remains the leading cause of HF; relevant for migrant populations with chronic rheumatic valve disease in Western settings.
To determine if digoxin, compared with placebo, improves the composite of death or new-onset or worsening heart failure in patients with symptomatic rheumatic heart disease. Design, Setting, and Participants: Multicenter, randomized, placebo-controlled trial enrolling patients with rheumatic heart disease who additionally had heart failure or atrial fibrillation or were already taking digoxin at 12 tertiary care hospitals in India between February 25, 2022, and August 31, 2024; median follow-up was 2.1 years (until December 15, 2025).
Patients were randomized 1:1, stratified by baseline rhythm, to receive oral digoxin 0.125 to 0.25 mg once daily (n=885) or matching placebo (n=884). Main Outcomes and Measures: The primary outcome was a composite of all-cause death or new-onset or worsening heart failure within 36 months of follow-up or until study end, whichever occurred first.
Of 1769 enrolled patients, 1759 took at least 1 dose. Mean age was 46 years and 72% were female. Most (81.5%) had mixed lesions involving multiple valves, with 85% having moderate to severe mitral stenosis. Atrial fibrillation was present in 70%, and 90% were in NYHA class II-IV. The primary composite outcome occurred in 276 patients (31.4%) receiving digoxin and 312 (35.5%) receiving placebo (hazard ratio 0.82; 95% CI 0.69-0.96).
In patients with symptomatic rheumatic heart disease, digoxin reduced the composite of death or new-onset or worsening heart failure compared with placebo.
