Efficacy and safety of sustained (48 hour) intravenous infusions of milrinone in patients with severe congestive heart failure: A multicenter study

• Published in: Journal of the American College of Cardiology 1987-04, Vol.9 (4), p.711-722
• Main Authors: Anderson, Jeffrey L., Baim, Donald S., Fein, Steven A., Goldstein, Richard A., LeJemtel, Thierry H., Likoff, Mariell J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Cardiotonic agents; Cardiotonic Agents - therapeutic use; Cardiovascular system; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Heart Failure - drug therapy; Hemodynamics - drug effects; Humans; Infusions, Intravenous - methods; Kinetics; Male; Medical sciences; Middle Aged; Milrinone; Pharmacology. Drug treatments; Placebos; Pyridones - administration & dosage; Pyridones - blood; Pyridones - therapeutic use
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(87)80223-1

Milrinone is a new bipyridine inotrope that has shown promise in initial clinical testing when administered intravenously or orally. The present multicenter study was designed to evaluate the clinical effectiveness and safety of sustained (48 hour) intravenous infusions of different doses of milrinone, as would be used clinically, in a controlled fashion using invasive hemodynamic monitoring. Entry was limited to adult patients with chronic heart failure of functional class III or IV, with a cardiac index ≤2.5 liters/min per m2or a pulmonary capillary wedge pressure ≥15 mm Hg, or both. After stable baseline hemodynamic recordings were obtained, milrinone was given as loading (μg/kg per 10 min) and maintenance infusions (μg/kg per min) to 189 patients in one of four loading/maintenance dosage regimens: 37.5/0.375 (low dose, n = 26), 50/0.50 (intermediate dose, n = 95), 75/0.75 (high dose, n = 15) and 50/0.25 (lowest dose, n = 53). The lowest dose was shown to be ineffective for maintenance therapy. Effective individual patient responses were defined as ≥20% increase in cardiac index or decrease in pulmonary capillary wedge pressure, or both. During early therapy (≤3 hour), 99% of patients showed an effective maximal response, and 90% an effective mean response. An effective mean response was observed during days 1 and 2 in 80% of patients, with a positive dose-response trend (69% response, low dose; 80%, intermediate dose; 93%, high dose; day I). Each loading regimen was effective, with maximal mean response occurring at 15 minutes. Cardiac index initially increased by an average of 24 to 42% for all patients in the three groups, whereas pulmonary capillary wedge pressure decreased by 24 to 33%. Initial decreases in systemic vascular resistance averaged 15 to 31%. Initial changes in heart rate ( + 4 to +13%) and mean arterial pressure (− 2 to −13%) were modest. Significant mean hemodynamic responses were maintained over the 48 hours. Increases in cardiac index for days 1 and 2 averaged 38 and 39% for those completing constant low dose drug, 34 and 37% for intermediate dose and 73 and 44% for high dose. Decreases in pulmonary capillary wedge pressure for all patients averaged 18 to 32% on days 1 and 2, with little dose response. Heart rate changes were modest and variable, averaging − 9 to 9%. Mean arterial pressure decreased slightly (2 to 6%) for the lower doses and moderately (8 to 16%) for the high dose. Reductions in systemic vascular resistance average