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Cited by 279Atrial Fibrillation Management and OutcomesHeart Failure Treatment and ManagementPharmaceutical Practices and Patient Outcomes

Increased mortality among patients taking digoxin—analysis from the AFFIRM study

Whitbeck, M. G., Charnigo, R. J., Khairy, P., Ziada, K., Bailey, A. L., Zegarra, M. M., Shah, J., Morales, G. +15 more·2013·European Heart Journal
DOI 10.1093/eurheartj/ehs348
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Abstract

AIMS: Digoxin 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 RESULTS: The 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. CONCLUSION: Digoxin 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.

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Crossref · 10.1093/eurheartj/ehs348

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  • Observational studies have associated digoxin use with excess mortality in AF patients.

    “Observational studies have associated digoxin use with excess mortality in AF patients, [547][548][549] but this association is likely due to selection and prescription biases rather than harm caused by digoxin, [550][551][552][553] particularly as digoxin is commonly prescribed to sicker patients.225”

    From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [549]

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Authors
Whitbeck, M. G., Charnigo, R. J., Khairy, P., Ziada, K., Bailey, A. L., Zegarra, M. M., Shah, J., Morales, G., Macaulay, T., Sorrell, V. L., Campbell, C. L., Gurley, J., Anaya, P., Nasr, H., Bai, R., Di Biase, L., Booth, D. C., Jondeau, G., Natale, A., Roy, D., Smyth, S., Moliterno, D. J., & Elayi, C. S.
Affiliations
University of Kentucky (US)
Corresponding author
Elayi, C. S.
ORCID
Venue
European Heart Journal
Publisher
Oxford University Press (OUP)
Published
2012-11-27
Volume
34
Issue
20
Pages
1481-1488
ISSN
  • 0195-668X (ISSN-L)
  • 1522-9645
DOI
10.1093/eurheartj/ehs348
OpenAlex
W2167141372
Cited by
279
References
45
Citations by year
2026: 5 · 2025: 6 · 2024: 9 · 2023: 7 · 2022: 16 · 2021: 20 · 2020: 19 · 2019: 13 · 2018: 18 · 2017: 25 · 2016: 38 · 2015: 35 · 2014: 43 · 2013: 22 · 2012: 2
FWCI
21.00
Type
journal article
Language
en
Open access
closed
Locations
  • European Heart Journal (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
Keywords
digoxin, atrial fibrillation, mortality, all-cause mortality, cardiovascular mortality, arrhythmic mortality, heart failure, rate control, drug safety, comorbidities, gender differences
MeSH terms
Aged, Anti-Arrhythmia Agents, Atrial Fibrillation, Cause of Death, Digoxin, Female, Heart Failure, Humans, Male, Proportional Hazards Models, Kaplan-Meier Estimate

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