Evidence map›Paper›PMID 23186806›Full record

Trial reportEuropean heart journal2013

Increased mortality among patients taking digoxin--analysis from the AFFIRM study.

Matthew G Whitbeck, Richard J Charnigo, Paul Khairy, Khaled Ziada, Alison L Bailey, Milagros M Zegarra, Jignesh Shah, Gustavo Morales, Tracy Macaulay, Vincent L Sorrell and 13 more

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in European heart journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 8 pooled it
19.5field-weighted citation impact, top 1% of its field
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

95 citing papers in PubMed, 8 syntheses or guidelines pooled it, 279 citations in OpenAlex.

  1. Pooled it
  2. Population Pharmacokinetic Studies of Digoxin in Adult Patients: A Systematic Review.European journal of drug metabolism and pharmacokinetics · 2021
    Pooled it
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  8. Guideline
  9. Modelling anticoagulation and health-related quality of life in those with atrial fibrillation: a secondary analysis of AFFIRM.Clinical research in cardiology : official journal of the German Cardiac Society · 2024
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  12. Trial
  13. Review
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  16. Article
  17. Digitalis Therapy Is Associated With an Increased Risk of ICD Shock Delivery and Device Revision.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2025
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35 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 1 institution in 1 country.

Matthew G WhitbeckDivision of Cardiovascular Medicine, Gill Heart Institute University of Kentucky, 900 South Limestone Street, Lexington, KY 40536-0200, USA.
Richard J Charnigo
Paul Khairy
Khaled Ziada
Alison L Bailey
Milagros M Zegarra
Jignesh Shah
Gustavo Morales
Tracy Macaulay
Vincent L Sorrell
Charles L Campbell
John Gurley
Paul Anaya
Hafez Nasr
Rong Bai
Luigi Di Biase
David C Booth
Guillaume Jondeau
Andrea Natale
Denis Roy
Susan Smyth
David J Moliterno
Claude S Elayi
University of Kentucky · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsDigoxin is frequently used for rate control of atrial fibrillation (AF). It has, however, been associated with increased mortality. It remains unclear whether digoxin itself is responsible for the increased mortality (toxic drug effect) or whether it is prescribed to sicker patients with inherently higher mortality due to comorbidities. The goal of our study was to determine the relationship between digoxin and mortality in patients with AF. METHODS AND

resultsThe association between digoxin and mortality was assessed in patients enrolled in the AF Follow-Up Investigation of Rhythm Management (AFFIRM) trial using multivariate Cox proportional hazards models. Analyses were conducted in all patients and in subsets according to the presence or absence of heart failure (HF), as defined by a history of HF and/or an ejection fraction <40%. Digoxin was associated with an increase in all-cause mortality [estimated hazard ratio (EHR) 1.41, 95% confidence interval (CI) 1.19-1.67, P < 0.001], cardiovascular mortality (EHR 1.35, 95% CI 1.06-1.71, P = 0.016), and arrhythmic mortality (EHR 1.61, 95% CI 1.12-2.30, P = 0.009). The all-cause mortality was increased with digoxin in patients without or with HF (EHR 1.37, 95% CI 1.05-1.79, P = 0.019 and EHR 1.41, 95% CI 1.09-1.84, P = 0.010, respectively). There was no significant digoxin-gender interaction for all-cause (P = 0.70) or cardiovascular (P = 0.95) mortality.

conclusionDigoxin was associated with a significant increase in all-cause mortality in patients with AF after correcting for clinical characteristics and comorbidities, regardless of gender or of the presence or absence of HF. These findings call into question the widespread use of digoxin in patients with AF.

Indexed as

AgedAnti-Arrhythmia AgentsAtrial FibrillationCause of DeathDigoxinFemaleHeart FailureHumansKaplan-Meier EstimateMaleProportional Hazards ModelsAnti-Arrhythmia AgentsDigoxinArrhythmiasAtrial fibrillationCongestive heart failureDigoxinMortality

Identifiers

PMID23186806
OpenAlexW2167141372

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.