{"id":"ea18408b5784","type":"article","url":"https://hartvaat.nl/2019/10/21/digoxine-en-mortaliteit-gerandomiseerd-versus-observationeel-in-de-dig-trial/","title":"Digoxine en mortaliteit: gerandomiseerd versus observationeel in de DIG-trial","title_en":"Digoxin-mortality: randomized vs. observational comparison in the DIG trial.","category":"hartfalen","category_label":"Hartfalen","professions":["cardioloog"],"tags":[],"journal":"European heart journal","doi":"10.1093/eurheartj/ehz395","source_url":"https://doi.org/10.1093/eurheartj/ehz395","authors":["Lukas Aguirre Dávila","Kristina Weber","Udo Bavendiek","Johann Bauersachs","Janet Wittes","Salim Yusuf","Armin Koch"],"significance":6,"published":"2019-10-21","source_date":"2019-10-21","image":"","kennis":[],"congress":"","summary_en":"This DIG trial analysis compared randomized with observational mortality estimates for digoxin, demonstrating how non-randomized analyses can produce misleading conclusions about drug safety due to confounding by indication.","created":"2026-07-03T10:28:12Z","updated":"2026-07-03T13:27:23Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Analyse die gerandomiseerde versus observationele mortaliteitsdata voor digoxine vergeleek in de DIG-trial. Methodologisch relevant voor het digoxinedebat.","abstract_original":"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the 6800 patients in the DIG trial had been treated with digoxin before randomization, and half of them were randomly withdrawn from digoxin treatment.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 < 0.001] and heart failure hospitalizations (HR 1.47, 95% CI 1.33-1.61; P < 0.001) were significantly higher in patients pre-treated with digoxin even after adjustment for baseline population differences. The higher risks for both outcomes in those who had previously received digoxin persisted even if they received placebo during the trial (HR 1.24, 95% CI 1.10-1.40; P < 0.001). This sharply contradicts the neutral effect on mortality and the significant reduction in heart failure hospitalizations observed in the randomized comparison. CONCLUSION: Prescription of digoxin is an indicator of disease severity and worse prognosis, which cannot be fully accounted for by covariate adjustments in the DIG trial where patients were well-characterized. It is unlikely that weaker research approaches (observational studies of administrative data or registries) can provide more reliable estimates of the effects of cardiac glycosides."}