Enoximone (MDL 17,043) for stable, chronic heart failure secondary to ischemic or idiopathic cardiomyopathy.
To examine the efficacy and safety of enoximone for treatment of patients with chronic, clinically stable cardiac failure secondary to ischemic or myopathic heart disease, 31 patients were enrolled into an early phase II trial. The hemodynamic response to intravenous and oral enoximone was assessed and compared with the response to dobutamine therapy (5 to 10 micrograms/kg/min). Maximal O2 uptake, an objective measure of effort tolerance, was serially monitored. Intravenous (1 to 2 mg/kg) and oral (1 to 2 mg/kg) enoximone improved (p less than 0.05) cardiac index while reducing right atrial and wedge pressures to a greater extent than dobutamine. The salutary hemodynamic response to oral enoximone was sustained for 6 to 8 hours and was not associated with subacute drug tolerance. Maximal O2 uptake was increased (p less than 0.05) at 2, 4, 8, 12, 24 and 52 weeks of oral enoximone therapy (1.4 +/- 0.5 mg/kg every 8 hours) while radionuclide ejection fraction at 65 weeks increased (p less than 0.05) from baseline (39 +/- 16% vs 30 +/- 9%). Nine patients, 8 of whom were in functional class III or IV on enrollment, died after a mean of 18 weeks: 4 from cardiac failure and 5 suddenly. Two patients had adverse gastrointestinal effects. Oral enoximone (1 to 2 mg/kg every 8 hours) appears to be useful in the short- and long-term management of clinically stable, chronic cardiac failure. Controlled phase III trials are warranted.
D000284:Administration, Oral; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004280:Dobutamine / Q000627:therapeutic use; D004341:Drug Evaluation; D017335:Enoximone; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007275:Injections, Intravenous; D005082:Physical Exertion
D002316:Cardiotonic Agents; D007093:Imidazoles; D004280:Dobutamine; D017335:Enoximone