title: Increased mortality among patients taking digoxin--analysis from the AFFIRM study.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiovascular Medicine, Gill Heart Institute University of Kentucky, 900 South Limestone Street, Lexington, KY 40536-0200, USA.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Whitbeck
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Charnigo
authors.forename: Paul
authors.initials: P
authors.lastname: Khairy
authors.forename: Khaled
authors.initials: K
authors.lastname: Ziada
authors.forename: Alison L
authors.initials: AL
authors.lastname: Bailey
authors.forename: Milagros M
authors.initials: MM
authors.lastname: Zegarra
authors.forename: Jignesh
authors.initials: J
authors.lastname: Shah
authors.forename: Gustavo
authors.initials: G
authors.lastname: Morales
authors.forename: Tracy
authors.initials: T
authors.lastname: Macaulay
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Sorrell
authors.forename: Charles L
authors.initials: CL
authors.lastname: Campbell
authors.forename: John
authors.initials: J
authors.lastname: Gurley
authors.forename: Paul
authors.initials: P
authors.lastname: Anaya
authors.forename: Hafez
authors.initials: H
authors.lastname: Nasr
authors.forename: Rong
authors.initials: R
authors.lastname: Bai
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Biase
authors.forename: David C
authors.initials: DC
authors.lastname: Booth
authors.forename: Guillaume
authors.initials: G
authors.lastname: Jondeau
authors.forename: Andrea
authors.initials: A
authors.lastname: Natale
authors.forename: Denis
authors.initials: D
authors.lastname: Roy
authors.forename: Susan
authors.initials: S
authors.lastname: Smyth
authors.forename: David J
authors.initials: DJ
authors.lastname: Moliterno
authors.forename: Claude S
authors.initials: CS
authors.lastname: Elayi
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D002423:Cause of Death; D004077:Digoxin / Q000009:adverse effects*; D005260:Female; D006333:Heart Failure / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D016016:Proportional Hazards Models
chemical_list: D000889:Anti-Arrhythmia Agents; D004077:Digoxin