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 journalArticlepeer-review

223 Scopus citations


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
Issue number20
StatePublished - May 21 2013
Externally publishedYes


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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Increased mortality among patients taking digoxin - Analysis from the AFFIRM study'. Together they form a unique fingerprint.

Cite this