Efficacy of phosphodiesterase inhibition with milrinone in combination with converting enzyme inhibitors in patients with heart failure

Efficacy of phosphodiesterase inhibition with milrinone in combination with converting enzyme inhibitors in patients with heart failure

We describe the results of two placebo-controlled trials (MIL-1077 and MIL-1078) designed to evaluate the clinical efficacy of oral milrinone administered together with converting enzyme inhibitors to patients with congestive heart failure. Although these trials were terminated prematurely, they pro...

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Bibliographic Details
Published in:Journal of the American College of Cardiology Vol. 22; no. 4; pp. A113 - A118
Main Authors: Colucci, Wilson S., Sonnenblick, Edmund H., Adams, Kirkwood F., Berk, Martin, Brozena, Susan C., Cowley, Allan J., Grabicki, James M., Kubo, Spencer A., LeJemtel, Thierry, Littler, William A., Shabetai, Ralph, Shannon, James, Starling, Mark R., Touchon, Robert C., Wasserman, Alan G., The Milrinone Multicenter Trials Investigators
Format: Journal Article Conference Proceeding
Language:English
Published: New York, NY Elsevier Inc 01-10-1993
Elsevier Science
Subjects:
Biological and medical sciences
Cardiotonic agents
Cardiovascular system
Medical sciences
Pharmacology. Drug treatments
Human
Heart failure
Drug combination
Enzyme
Oral administration
Enzyme inhibitor
Cardiovascular disease
Route of administration
Chemotherapy
Cyclic-nucleotide phosphodiesterase
Treatment
Heart disease
Angiotensin converting enzyme
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Summary:We describe the results of two placebo-controlled trials (MIL-1077 and MIL-1078) designed to evaluate the clinical efficacy of oral milrinone administered together with converting enzyme inhibitors to patients with congestive heart failure. Although these trials were terminated prematurely, they provide the only controlled data regarding the effect of oral milrinone on exercise capacity in patients receiving converting enzyme inhibitors. Of the 254 patients randomized, 140 completed one of the trials or reached an end point and are the basis of this report. In both trials, there was a clear trend for an increase in exercise capacity in the milrinone-treated patients (+ 26 ± 8% vs. +5 ± 7% in MIL-1077 and + 11 ± 5% vs. + 2 ± 4% in MIL-1078). Symptoms of congestive heart failure were decreased in one trial but not the other. Quality of life, as assessed by a questionnaire, was not effected in either trial. There was an increased incidence of adverse events in milrinone-treated patients. Adverse events related primarily to hypotension and vasodilation led to discontinuation of drug in 18 milrinone-treated patients vs. 1 placebo-treated patient. Milrinone had little or no proarrhythmic effect and cardiovascular deaths were distributed equally between the milrinone and placebo groups. These data suggest that when used in combination with a converting enzyme inhibitor, oral milrinone improves exercise capacity but is associated with a high incidence of adverse events that appear to be related to excessive vasodilation.
ISSN:0735-1097
1558-3597
DOI:10.1016/0735-1097(93)90473-E