Evidence map›Paper›PMID 31211324›Full record

SynthesisEuropean heart journal2019

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

Lukas Aguirre Dávila, Kristina Weber, Udo Bavendiek, Johann Bauersachs, Janet Wittes, Salim Yusuf, Armin Koch

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in European heart journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

  1. Simple and safe digitoxin dosing in heart failure based on data from the DIGIT-HF trial.Clinical research in cardiology : official journal of the German Cardiac Society · 2023
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  4. Mechanical circulatory support for cardiogenic shock in takotsubo syndrome.Clinical research in cardiology : official journal of the German Cardiac Society · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Lukas Aguirre DávilaInstitute for Biostatistics, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany.
Kristina WeberInstitute for Biostatistics, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany.
Udo BavendiekDepartment of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Johann BauersachsDepartment of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Janet WittesStatistics Collaborative, Inc., Washington, DC, USA.
Salim YusufPopulation Health Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
Armin KochInstitute for Biostatistics, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThe 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

resultsForty-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.

conclusionPrescription 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.

Indexed as

Cardiotonic AgentsDigoxinHeart FailureBiasHumansObservational Studies as TopicRandomized Controlled Trials as TopicCardiotonic AgentsDigoxinCardiac glycosidesDigoxinHeart failureMortalityPrescription biasRandomization

Identifiers

PMID31211324
PMCPMC6801940

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.