title: Relationship of serum digoxin concentration to mortality and morbidity in women in the digitalis investigation group trial: a retrospective analysis.
abstract: OBJECTIVE
  The purpose of this study was to investigate the relationship of serum digoxin concentration (SDC) and outcomes in women with heart failure (HF).
  
  
  BACKGROUND
  Controversy continues concerning the clinical utility of digoxin in women with HF.
  
  
  METHODS
  Our analysis was retrospective with data from the Digitalis Investigation Group (DIG) trial. The principal study analysis reviewed 4,944 patients with HF due to systolic dysfunction who survived for at least 4 weeks (all 3,366 patients randomized to placebo and the 1,578 of 3,372 patients randomized to digoxin who had serum concentration measured 6 to 30 h [inclusive] after the last dose of study drug at 4 weeks).
  
  
  RESULTS
  Continuous multivariable analysis demonstrated a significant linear relationship between SDC and mortality in women (p = 0.008) and men (p = 0.002, p = 0.766 for gender interaction). Averaging hazard ratios (HRs) across serum concentrations from 0.5 to 0.9 ng/ml in women produced a HR for death of 0.8 (95% confidence interval [CI] 0.62 to 1.13, p = 0.245) and for death or hospital stay for worsening HF of 0.73 (95% CI 0.58 to 0.93, p = 0.011). In contrast, SDCs from 1.2 to 2.0 ng/ml were associated with a HR for death for women of 1.33 (95% CI 1.001 to 1.76, p = 0.049).
  
  
  CONCLUSIONS
  Retrospective analysis of data from the DIG trial indicates a beneficial effect of digoxin on morbidity and no excess mortality in women at serum concentrations from 0.5 to 0.9 ng/ml, whereas serum concentrations > or =1.2 ng/ml seem harmful.
authors.affiliation: Department of Medicine and Radiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27517, USA. kfa@med.unc.edu
authors.forename: Kirkwood F
authors.initials: KF
authors.lastname: Adams
authors.forename: J Herbert
authors.initials: JH
authors.lastname: Patterson
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Gattis
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.forename: Craig R
authors.initials: CR
authors.lastname: Lee
authors.forename: Todd A
authors.initials: TA
authors.lastname: Schwartz
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
mesh_terms: D000367:Age Factors; D000368:Aged; D001682:Biological Availability; D002316:Cardiotonic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016001:Confidence Intervals; D004077:Digoxin / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015999:Multivariate Analysis; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D002316:Cardiotonic Agents; D004077:Digoxin