title: Low-dose oral enoximone enhances the ability to wean patients with ultra-advanced heart failure from intravenous inotropic support: results of the oral enoximone in intravenous inotrope-dependent subjects trial.
abstract: BACKGROUND
  We determined whether low-dose oral enoximone could wean patients with ultra-advanced heart failure (UA-HF) from intravenous (i.v.) inotropic support. Chronic parenteral inotropic therapy in UA-HF is costly and requires an indwelling catheter. An effective and safe oral inotrope would have value.
  
  
  METHODS
  In this placebo-controlled study, 201 subjects with UA-HF requiring i.v. inotropic therapy were randomized to enoximone or placebo. Subjects receiving intermittent i.v. inotropes were administered study medication of 25 or 50 mg 3 times a day (tid). Subjects receiving continuous i.v. inotropes were administered 50 or 75 mg tid for 1 week, which was reduced to 25 or 50 mg tid. The ability of subjects to remain alive and free of inotropic therapy was assessed for up to 182 days.
  
  
  RESULTS
  Thirty days after weaning, 51 (51%) subjects on placebo and 62 (61.4%) subjects in the enoximone group were alive and free of i.v. inotropic therapy (unadjusted primary end point P = 0.14, adjusted for etiology P = .17). At 60 days, the wean rate was 30% in the placebo group and 46.5% in the enoximone group (unadjusted P = .016) Kaplan-Meier curves demonstrated a trend toward a decrease in the time to death or reinitiation of i.v. inotropic therapy over the 182-day study period (hazard ratio 0.76 [95% CI 0.55-1.04]) and a reduction at 60 days (0.62 [95% CI 0.43-0.89], P = .009) and 90 days (0.69 [95% CI 0.49-0.97], P = .031) after weaning in the enoximone group.
  
  
  CONCLUSIONS
  Although there was no benefit over placebo in weaning patients from i.v. inotropes from 0 to 30 days, the EMOTE data suggest that low-dose oral enoximone can be used to wean a modest percentage of subjects from i.v. inotropic support for up to 90 days after initiation of therapy.
authors.affiliation: Department of Medicine, Jefferson Medical College, Philadelphia, PA 19107, USA.
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Feldman
authors.forename: Ron M
authors.initials: RM
authors.lastname: Oren
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
authors.forename: John P
authors.initials: JP
authors.lastname: Boehmer
authors.forename: Peter E
authors.initials: PE
authors.lastname: Carson
authors.forename: Eric
authors.initials: E
authors.lastname: Eichhorn
authors.forename: Edward M
authors.initials: EM
authors.lastname: Gilbert
authors.forename: Andrew
authors.initials: A
authors.lastname: Kao
authors.forename: Carl V
authors.initials: CV
authors.lastname: Leier
authors.forename: Brian D
authors.initials: BD
authors.lastname: Lowes
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mathier
authors.forename: Frank A
authors.initials: FA
authors.lastname: McGrew
authors.forename: Marco
authors.initials: M
authors.lastname: Metra
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Zisman
authors.forename: Simon F
authors.initials: SF
authors.lastname: Shakar
authors.forename: Steven K
authors.initials: SK
authors.lastname: Krueger
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Robertson
authors.forename: Bill G
authors.initials: BG
authors.lastname: White
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gerber
authors.forename: Gwyn E
authors.initials: GE
authors.lastname: Wold
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bristow
mesh_terms: D000284:Administration, Oral; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D017335:Enoximone / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D002316:Cardiotonic Agents; D017335:Enoximone