Evaluation of a New Bipyridine Inotropic Agent — Milrinone — in Patients with Severe Congestive Heart Failure

Milrinone, a derivative of amrinone, has nearly 20 times the inotropic potency of the parent compound and does not cause fever or thrombocytopenia in normal volunteers or in animals sensitive to amrinone. In 20 patients with severe congestive heart failure, intravenous milrinone resulted in significant decreases in left ventricular end-diastolic pressure (from 27±2 to 18±2 mm Hg), pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance, as well as a slight reduction in mean arterial pressure. Significant increases occurred in cardiac index (from 1.9±0.1 to 2.9±0.2 liters per minute per square meter) and the peak positive first derivative of left ventricular pressure, with a slight increase in heart rate. Hemodynamic improvement was sustained during a 24-hour continuous infusion. Nineteen of the 20 patients subsequently received oral milrinone (29±2 mg per day) for up to 11 months (mean, 6.0±0.8), with sustained improvement in symptoms of heart failure. In 10 patients receiving long-term oral milrinone (≥6 months) radionuclide ventriculography showed continued responsiveness, with a 27 per cent increase in left ventricular ejection fraction after 7.5 mg of the drug. Four patients died after a mean of 4.8 months of therapy, and three patients with severe underlying coronary-artery disease and angina pectoris required additional antianginal therapy. No patient had fever, thrombocytopenia, gastrointestinal intolerance, or aggravation of ventricular ectopy. We conclude that milrinone shows promise for the long-term treatment of congestive heart failure. (N Engl J Med 1983;309:748–56). DESPITE the development of a variety of potent arterial and venous vasodilators,¹ the cardiac glycosides continue to occupy a central role in the therapy of chronic congestive heart failure. As compared with currently available intravenous agents such as dopamine and dobutamine, however, the cardiac glycosides have a relatively weak inotropic effect and a narrow toxic-to therapeutic ratio.² The search for more potent, orally active inotropic agents has recently led to the development of amrinone,^3,4 a bipyridine compound whose intravenous^5,6 or oral^7,8 administration results in substantial acute hemodynamic improvement in patients with congestive heart failure, as well as sustained improvement in.