Use of digoxin in atrial fibrillation: One step further in the mortality controversy from the AFFIRM study

Richard Charnigo, Paul Khairy, Jing Guo, Azadeh Shohoudi, Claude S. Elayi

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background: Whether there is a causal association between digoxin and mortality among patients with atrial fibrillation (AF), with or without congestive heart failure (HF), has been controversial; in particular, two prior analyses of data from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial have yielded conflicting results. We sought to investigate how digoxin impacts mortality, in the full AFFIRM cohort and for various subgroups, by applying marginal structural modeling (MSM) to AFFIRM data. Methods: MSM is a newer statistical approach, which estimates causal association in the absence of randomization. MSM more effectively accounts for time-varying treatment and mitigates potential biases, in contrast to the two statistical approaches used in prior analyses of the AFFIRM data. Results: Among 4,060 patients in AFFIRM, 660 (16.3%) died during follow-up. Digoxin was associated with significantly higher mortality in the full cohort (estimated hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.11–1.60, P = 0.002) and in 3,121 patients without HF (HR 1.36, 95% CI 1.07–1.72, P = 0.011). There was a trend toward higher mortality with digoxin in 939 patients with HF (HR 1.29, 95% CI 0.96–1.72, P = 0.090). Associations were nonsignificant in 463 patients with HF and left ventricular ejection fraction (EF) ≥40% and in 155 patients with EF ≤30%. Conclusions: Digoxin is associated with significantly increased mortality among AFFIRM patients collectively, as determined by MSM statistical methodology. However, the impact of digoxin among AFFIRM patients with coexisting HF is inconclusive.

Original languageEnglish
Pages (from-to)713-719
Number of pages7
JournalPACE - Pacing and Clinical Electrophysiology
Issue number7
StatePublished - Jul 2018

Bibliographical note

Publisher Copyright:
© 2018 Wiley Periodicals, Inc.


  • arrhythmia
  • cardiomyopathy
  • congestive heart failure
  • heart failure with preserved ejection fraction
  • marginal structural modeling
  • systolic dysfunction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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