Closing the Digitalis Divide: Back to the Basics of Randomized Controlled Trials

• Published in: Cardiovascular drugs and therapy Vol. 37; no. 4; pp. 807 - 813
• Main Authors: Triska, J., Uretsky, B. F., Pitt, B., Birnbaum, Y.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2023; Springer Nature B.V
• Subjects: Atrial Fibrillation - diagnosis; Atrial Fibrillation - drug therapy; Cardiology; Clinical trials; Congestive heart failure; Digitalis; Digoxin; Digoxin - adverse effects; Heart failure; Heart Failure - diagnosis; Heart Failure - drug therapy; Hospitalization; Humans; Medicine; Medicine & Public Health; Meta-analysis; Mortality; Randomized Controlled Trials as Topic; Review Article; Symptom management; Heart failure; Digoxin; Randomized controlled trial; Atrial fibrillation; Mortality; Meta-analysis
• ISSN: 0920-3206; 1573-7241; 1573-7241
• DOI: 10.1007/s10557-021-07287-8

Purpose Publishe d decades after several randomized controlled trials (RCT) demonstrating decreased hospitalizations and no effect on all-cause mortality with digoxin use, a series of meta-analyses linking digoxin treatment and mortality have contributed to a narrower application of this medication for the management of heart failure (HF) and atrial fibrillation (AF). Given the conflicting data from the earlier RCTs and more recent meta-analyses, there is a growing polarization among providers for and against the use of digoxin in managing these conditions. Methods To help close this divide, we provide a perspective on the literature with special attention to the quality of both older and more recent studies on this subject. Results The data from the highest quality studies we have, RCTs, suggest that digoxin use in patients with HF and/or AF is associated with improvement in several areas of outcomes including functional capacity, symptom management, reduced hospitalizations, fewer deaths due to HF, and treatment of refractory chronic heart failure with rEF, and may even have overall mortality benefit when serum digoxin concentrations are within therapeutic range. These effects are more pronounced in patients with EF < 25% and NYHA Class II–IV and at highest risk for hospitalization. Conclusion As the risk of confounding factors was minimized by the study design, the likelihood that positive outcomes were identified with digoxin use increased. Clinicians and researchers need further adequately designed and powered RCTs exploring the connection between digoxin therapy and mortality, hospitalizations, and symptom management.