Digoxin–mortality: randomized vs. observational comparison in the DIG trial

• Published in: European heart journal 2019-10, Vol.40 (40), p.3336-3341
• Main Authors: Aguirre Dávila, Lukas, Weber, Kristina, Bavendiek, Udo, Bauersachs, Johann, Wittes, Janet, Yusuf, Salim, Koch, Armin
• Format: Article
• Language: English
• Subjects: Bias; Cardiotonic Agents - adverse effects; Cardiotonic Agents - therapeutic use; Clinical Research; Digoxin - adverse effects; Digoxin - therapeutic use; Heart Failure - drug therapy; Heart Failure - mortality; Humans; Observational Studies as Topic; Randomized Controlled Trials as Topic
• ISSN: 0195-668X; 1522-9645; 1522-9645
• DOI: 10.1093/eurheartj/ehz395

Abstract Aims The Digitalis Investigation Group (DIG) trial, the only large randomized trial of digoxin in heart failure, reported a neutral effect on mortality and a significant reduction in heart failure hospitalizations. Recent observational studies reported increased mortality with digoxin treatment. We present further analyses of the DIG trial displaying the inability to control bias in observational treatment comparisons despite extensive statistical adjustments. Methods and results Forty-four percent of the 6800 patients in the DIG trial had been treated with digoxin before randomization, and half of them were randomly withdrawn from digoxin treatment. We contrast the main randomization-based result of the DIG trial with the observational non-randomized comparison of patients pre-treated or not pre-treated with digoxin. Mortality [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.12–1.34; P