Trial reportJournal of the American Heart Association2017
Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF-TIMI 48 Trial.
Trial report in Journal of the American Heart Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00781391 (A Phase 3, Randomized, Double-Blind, Double-Dummy, Parallel Group, Multi-Center, Multi-National Study for Evaluation of Efficacy and Safety of Edoxaban), which is not on this map. Cited by 22 papers, 4 of them syntheses that pooled 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.
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.
A Phase 3, Randomized, Double-Blind, Double-Dummy, Parallel Group, Multi-Center, Multi-National Study for Evaluation of Efficacy and Safety of Edoxaban (DU-176b) Versus Warfarin In Subjects With Atrial Fibrillation - Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation (ENGAGE - AF TIMI - 48)
Who cites it
22 citing papers in PubMed, 4 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Effect of Digoxin Therapy on Mortality in Patients With Atrial Fibrillation: An Updated Meta-Analysis.Frontiers in cardiovascular medicine · 2021Pooled it
- Digoxin-mortality: randomized vs. observational comparison in the DIG trial.European heart journal · 2019Pooled it
- Pooled it
- Association is not causation: treatment effects cannot be estimated from observational data in heart failure.European heart journal · 2018Pooled it
- Reconsidering Digoxin in Atrial Fibrillation: From Historical Controversy to Physiologically Guided and Personalized Rate Control.Biomedicines · 2025Review
- Anticoagulation Therapies and microRNAs in Heart Failure.Biomolecules · 2025Review
- Divergent Electrophysiologic Effects of Sacubitril in Digitalis- and Pinacidil-Related Shortened Repolarization: Experimental Evidence for Harmful Effects of Digitalis Glycosides.Pharmaceutics · 2025Article
- Characterizing Utilization and Outcomes of Digoxin Immune Fab for Digoxin Toxicity.Drugs - real world outcomes · 2024Article
- Digoxin use and outcomes after myocardial infarction in patients with atrial fibrillation.Basic & clinical pharmacology & toxicology · 2022Article
- Digoxin Impact on Heart Failure Patients with Atrial Fibrillation.Medical archives (Sarajevo, Bosnia and Herzegovina) · 2022Article
- Association of digoxin therapy with case fatality rate in acute pulmonary embolism.Wiener klinische Wochenschrift · 2021Article
- A Visual Resolution of Cardiotoxicity: A Case Report of Digoxin-Induced Bidirectional Ventricular Tachycardia.Cureus · 2021Article
- Prognosis and management of new-onset atrial fibrillation in critically ill patients.BMC cardiovascular disorders · 2021Observational
- Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1International journal of molecular sciences · 2021Article
- Hemodynamic characteristics and early warnings in very old patients.American journal of translational research · 2021Review
- Current challenges in sudden cardiac death prevention.Heart failure reviews · 2020Review
- Biomimetic nanoparticle technology for cardiovascular disease detection and treatment.Nanoscale horizons · 2020Review
- Saudi Heart Association (SHA) guidelines for the management of heart failure.Journal of the Saudi Heart Association · 2019Review
- Digitalis therapy is associated with higher comorbidities and poorer prognosis in patients undergoing ablation of atrial arrhythmias: data from the German Ablation Registry.Clinical research in cardiology : official journal of the German Cardiac Society · 2019Article
- Atrial Fibrillation in the ICU.Chest · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDigoxin is widely used in patients with atrial fibrillation despite the lack of randomized controlled trials. Observational studies report conflicting results regarding its association with mortality, perhaps because of residual confounding by the presence of heart failure (HF). METHODS AND
resultsIn the ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial, clinical outcomes of patients with atrial fibrillation with and without HF were examined by baseline digoxin use during a median follow-up of 2.8 years. HF was defined at baseline as prior or current clinical stage C or D HF. Of 21 105 patients enrolled, 6327 (30%) were treated with digoxin at baseline. Among patients without HF (n=8981), digoxin use (20%) was independently associated with sudden cardiac death (adjusted hazard ratio, 1.51; 95% CI, 1.10-2.08), with no significant interaction by age, sex, left ventricular ejection fraction, renal function, or concomitant medications (
conclusionsIn this observational analysis of patients with atrial fibrillation without investigator-reported HF, digoxin use was significantly associated with sudden cardiac death. While residual confounding cannot be excluded, the association between digoxin use and worse clinical outcomes highlights the need to examine digoxin use, particularly when prescribed to control heart rate in patients with atrial fibrillation in a randomized trial. CLINICAL
trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00781391.
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Registered trials
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.