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: Arthur M Feldman, Ron M Oren, William T Abraham, John P Boehmer, Peter E Carson, Eric Eichhorn, Edward M Gilbert, Andrew Kao, Carl V Leier, Brian D Lowes, Michael A Mathier, Frank A McGrew, Marco Metra, Lawrence S Zisman, Simon F Shakar, Steven K Krueger, Alastair D Robertson, Bill G White, Michael J Gerber, Gwyn E Wold, Michael R Bristow, EMOTE Study Group
• Journal: American heart journal (Am Heart J) Vol. 154 Issue 5 Pg. 861-9 (Nov 2007) ISSN: 1097-6744 [Electronic] United States
• PMID: 17967591 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Enoximone

Topics

• Administration, Oral
• Cardiotonic Agents (administration & dosage)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Enoximone (administration & dosage)
• Female
• Follow-Up Studies
• Heart Failure (drug therapy, mortality, physiopathology)
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Myocardial Contraction (drug effects, physiology)
• Retrospective Studies
• Survival Rate
• Treatment Outcome
• United States (epidemiology)
• Ventricular Function, Left (drug effects, physiology)