title: Serum digoxin concentration and outcomes in women with heart failure: A bi-directional effect and a possible effect modification by ejection fraction.
abstract: BACKGROUND
  The association between serum digoxin concentration (SDC) and outcomes in women with heart failure (HF) has not been well studied.
  
  
  OBJECTIVE
  To test the hypothesis that the effect of digoxin on outcomes in women with HF is bi-directional and dependent on SDC, as in men, and is modified by ejection fraction (EF).
  
  
  METHODS
  We studied 1366 female participants of the Digitalis Investigation Group trial in whom data on SDC (ng/ml) were available. We calculated adjusted odds ratios (AOR) and Bonferroni-adjusted 97.5% confidence intervals (CI) for various outcomes at a median follow up of 41 months, in all women and stratified by EF 35%.
  
  
  RESULTS
  Compared with placebo (26.9%), 40.3% with SDC> or =1.2 (AOR=1.80; CI=1.14-2.86; p=0.004) and 26.6% with SDC 0.5-1.1 (AOR=1.05; CI=0.73-1.51; p=0.762) died. Respective rates for HF-hospitalizations were: placebo (32.8%), SDC> or =1.2 (38.0%) and SDC 0.5-1.1 (25.5%). For women with EF<35% (N=677), SDC 0.5-1.1 lowered odds for HF-hospitalizations (AOR=0.63; CI=0.39-1.00; p=0.026) without increasing odds for death (AOR=0.77; CI=0.47-1.26; p=0.233). In women with EF> or =35% (N=689), SDC 0.5-1.1 had a borderline association with death (AOR=1.58; CI=0.92-2.72; p=0.058) but not with HF-hospitalization (AOR=0.95; CI=0.54-1.66; p=0.826).
  
  
  CONCLUSIONS
  As in men, in women with HF, digoxin has a bi-directional effect based on SDC, and the beneficial effects were significant only among women with EF<35%.
authors.affiliation: Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. aahmed@uab.edu
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmed
authors.forename: Inmaculada B
authors.initials: IB
authors.lastname: Aban
authors.forename: Michael T
authors.initials: MT
authors.lastname: Weaver
authors.forename: Wilbert S
authors.initials: WS
authors.lastname: Aronow
authors.forename: Jerome L
authors.initials: JL
authors.lastname: Fleg
mesh_terms: D000368:Aged; D002303:Cardiac Output, Low / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D002316:Cardiotonic Agents / Q000097:blood* / Q000627:therapeutic use; D002423:Cause of Death; D002908:Chronic Disease; D004077:Digoxin / Q000097:blood* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D013318:Stroke Volume; D016896:Treatment Outcome
chemical_list: D002316:Cardiotonic Agents; D010919:Placebos; D004077:Digoxin