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, Charles L. Campbell, John Gurley, Paul Anaya, Hafez Nasr, Rong Bai, Luigi Di Biase, David C. Booth, Guillaume Jondeau, Andrea Natale, Denis RoySusan Smyth, David J. Moliterno, Claude S. Elayi

Research output: Contribution to journalArticle

157 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1481-1488
Number of pages8
JournalEuropean Heart Journal
Volume34
Issue number20
DOIs
StatePublished - May 21 2013
Externally publishedYes

Fingerprint

Digoxin
Mortality
Atrial Fibrillation
Confidence Intervals
Heart Failure
Comorbidity
Poisons
Proportional Hazards Models

Keywords

  • Arrhythmias
  • Atrial fibrillation
  • Congestive heart failure
  • Digoxin
  • Mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Whitbeck, M. G., Charnigo, R. J., Khairy, P., Ziada, K., Bailey, A. L., Zegarra, M. M., ... Elayi, C. S. (2013). Increased mortality among patients taking digoxin - Analysis from the AFFIRM study. European Heart Journal, 34(20), 1481-1488. https://doi.org/10.1093/eurheartj/ehs348

Increased mortality among patients taking digoxin - Analysis from the AFFIRM study. / Whitbeck, Matthew G.; Charnigo, Richard J.; Khairy, Paul; Ziada, Khaled; Bailey, Alison L.; Zegarra, Milagros M.; Shah, Jignesh; Morales, Gustavo; MacAulay, Tracy; Sorrell, Vincent L.; Campbell, Charles L.; Gurley, John; Anaya, Paul; Nasr, Hafez; Bai, Rong; Di Biase, Luigi; Booth, David C.; Jondeau, Guillaume; Natale, Andrea; Roy, Denis; Smyth, Susan; Moliterno, David J.; Elayi, Claude S.

In: European Heart Journal, Vol. 34, No. 20, 21.05.2013, p. 1481-1488.

Research output: Contribution to journalArticle

Whitbeck, MG, Charnigo, RJ, Khairy, P, Ziada, K, Bailey, AL, Zegarra, MM, Shah, J, Morales, G, MacAulay, T, Sorrell, VL, Campbell, CL, Gurley, J, Anaya, P, Nasr, H, Bai, R, Di Biase, L, Booth, DC, Jondeau, G, Natale, A, Roy, D, Smyth, S, Moliterno, DJ & Elayi, CS 2013, 'Increased mortality among patients taking digoxin - Analysis from the AFFIRM study', European Heart Journal, vol. 34, no. 20, pp. 1481-1488. https://doi.org/10.1093/eurheartj/ehs348
Whitbeck MG, Charnigo RJ, Khairy P, Ziada K, Bailey AL, Zegarra MM et al. Increased mortality among patients taking digoxin - Analysis from the AFFIRM study. European Heart Journal. 2013 May 21;34(20):1481-1488. https://doi.org/10.1093/eurheartj/ehs348
Whitbeck, Matthew G. ; Charnigo, Richard J. ; Khairy, Paul ; Ziada, Khaled ; Bailey, Alison L. ; Zegarra, Milagros M. ; Shah, Jignesh ; Morales, Gustavo ; MacAulay, Tracy ; Sorrell, Vincent L. ; Campbell, Charles L. ; Gurley, John ; Anaya, Paul ; Nasr, Hafez ; Bai, Rong ; Di Biase, Luigi ; Booth, David C. ; Jondeau, Guillaume ; Natale, Andrea ; Roy, Denis ; Smyth, Susan ; Moliterno, David J. ; Elayi, Claude S. / Increased mortality among patients taking digoxin - Analysis from the AFFIRM study. In: European Heart Journal. 2013 ; Vol. 34, No. 20. pp. 1481-1488.
@article{6c331ba43cf44ddc9f304bb642f19399,
title = "Increased mortality among patients taking digoxin - Analysis from the AFFIRM study",
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.",
keywords = "Arrhythmias, Atrial fibrillation, Congestive heart failure, Digoxin, Mortality",
author = "Whitbeck, {Matthew G.} and Charnigo, {Richard J.} and Paul Khairy and Khaled Ziada and Bailey, {Alison L.} and Zegarra, {Milagros M.} and Jignesh Shah and Gustavo Morales and Tracy MacAulay and Sorrell, {Vincent L.} and Campbell, {Charles L.} and John Gurley and Paul Anaya and Hafez Nasr and Rong Bai and {Di Biase}, Luigi and Booth, {David C.} and Guillaume Jondeau and Andrea Natale and Denis Roy and Susan Smyth and Moliterno, {David J.} and Elayi, {Claude S.}",
year = "2013",
month = "5",
day = "21",
doi = "10.1093/eurheartj/ehs348",
language = "English (US)",
volume = "34",
pages = "1481--1488",
journal = "European Heart Journal",
issn = "0195-668X",
publisher = "Oxford University Press",
number = "20",

}

TY - JOUR

T1 - Increased mortality among patients taking digoxin - Analysis from the AFFIRM study

AU - Whitbeck, Matthew G.

AU - Charnigo, Richard J.

AU - Khairy, Paul

AU - Ziada, Khaled

AU - Bailey, Alison L.

AU - Zegarra, Milagros M.

AU - Shah, Jignesh

AU - Morales, Gustavo

AU - MacAulay, Tracy

AU - Sorrell, Vincent L.

AU - Campbell, Charles L.

AU - Gurley, John

AU - Anaya, Paul

AU - Nasr, Hafez

AU - Bai, Rong

AU - Di Biase, Luigi

AU - Booth, David C.

AU - Jondeau, Guillaume

AU - Natale, Andrea

AU - Roy, Denis

AU - Smyth, Susan

AU - Moliterno, David J.

AU - Elayi, Claude S.

PY - 2013/5/21

Y1 - 2013/5/21

N2 - 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.

AB - 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.

KW - Arrhythmias

KW - Atrial fibrillation

KW - Congestive heart failure

KW - Digoxin

KW - Mortality

UR - http://www.scopus.com/inward/record.url?scp=84878304958&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878304958&partnerID=8YFLogxK

U2 - 10.1093/eurheartj/ehs348

DO - 10.1093/eurheartj/ehs348

M3 - Article

C2 - 23186806

AN - SCOPUS:84878304958

VL - 34

SP - 1481

EP - 1488

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - 20

ER -