title: Lack of evidence of increased mortality among patients with atrial fibrillation taking digoxin: findings from post hoc propensity-matched analysis of the AFFIRM trial.
abstract: OBJECTIVE
  Digoxin is recommended for long-term rate control in paroxysmal, persistent, and permanent atrial fibrillation (AF). While some analyses suggest an association of digoxin with a higher mortality in AF, the intrinsic nature of this association has not been examined in propensity-matched cohorts, which is the objective of the current study.
  
  
  RESULTS
  In Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), 4060 patients with paroxysmal and persistent AF were randomized to rate (n = 2027) vs. rhythm (n = 2033) control strategies. Of these, 1377 received digoxin as initial therapy and 1329 received no digoxin at baseline. Propensity scores for digoxin use were estimated for each of these 2706 patients and used to assemble a cohort of 878 pairs of patients receiving and not receiving digoxin, who were balanced on 59 baseline characteristics. Matched patients had a mean age of 70 years, 40% were women, and 11% non-white. During the 3.4 years of the mean follow-up, all-cause mortality occurred in 14 and 13% of matched patients receiving and not receiving digoxin, respectively [hazard ratio (HR) associated with digoxin use: 1.06; 95% confidence interval (CI): 0.83-1.37; P = 0.640]. Among matched patients, digoxin had no association with all-cause hospitalization (HR: 0.96; 95% CI: 0.85-1.09; P = 0.510) or incident non-fatal cardiac arrhythmias (HR: 0.90; 95% CI: 0.37-2.23; P = 0.827). Digoxin had no multivariable-adjusted or propensity score-adjusted associations with these outcomes in the pre-match cohort.
  
  
  CONCLUSIONS
  In patients with paroxysmal and persistent AF, we found no evidence of increased mortality or hospitalization in those taking digoxin as baseline initial therapy.
authors.affiliation: Northwestern University, Chicago, IL, USA.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: John G F
authors.initials: JG
authors.lastname: Cleland
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Epstein
authors.forename: Kanan
authors.initials: K
authors.lastname: Patel
authors.forename: Inmaculada B
authors.initials: IB
authors.lastname: Aban
authors.forename: Wilbert S
authors.initials: WS
authors.lastname: Aronow
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmed
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*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D057216:Propensity Score; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D004077:Digoxin
keywords: Atrial fibrillation; Digoxin; Hospitalization; Mortality; Propensity score