Digoxin in Patients With Symptomatic Rheumatic Heart Disease: A Randomized Clinical Trial.

Summary

In 1,759 symptomatic rheumatic heart disease patients, daily digoxin reduced the composite of all-cause death or new/worsening heart failure over a median 2.1 years (HR 0.82) mainly via fewer worsening HF events, without affecting all-cause mortality and with low toxicity-related discontinuation.

Key Findings

• Primary composite (all-cause death or new/worsening HF) reduced with digoxin vs placebo: HR 0.82 (95% CI 0.70-0.97; P=0.02).
• New-onset or worsening HF reduced: HR 0.82 (95% CI 0.69-0.98); most managed without hospitalization.
• All-cause mortality unchanged: HR 0.94 (95% CI 0.70-1.26).
• Low discontinuation due to suspected toxicity: 1.1% vs 0.1% (placebo).

Clinical Implications

Digoxin can be considered as adjunct therapy to reduce worsening HF events in symptomatic rheumatic heart disease, particularly in patients with atrial fibrillation, with careful dosing and monitoring.

Limitations

• Conducted in Indian tertiary centers with predominant mitral stenosis; generalizability to non-RHD or other settings may be limited.
• Not powered to detect mortality differences; serum digoxin levels and dose–response not detailed.

Future Directions

Evaluate dose optimization, therapeutic drug monitoring strategies, and applicability across diverse RHD phenotypes and resource settings; assess long-term mortality and quality-of-life effects.