Although
amrinone produces acute hemodynamic improvement in patients with severe chronic
congestive heart failure (CHF), it has not produced clinical benefits in long-term controlled trials. To determined if the administration of subtherapeutic doses of
amrinone may account for its lack of efficacy in these studies, the dose requirements of the
drug were investigated in 30 patients with severe CHF. Doses of 100 mg of oral
amrinone produced moderate increases in cardiac index (0.35 liters/min/m2) and decreases in pulmonary capillary wedge pressure (6.8 mm Hg) and systemic vascular resistance (16%) (all p less than 0.01); these effects, however, were short-lived (less than 2.5 hours). Doses of 200 mg of oral
amrinone produced marked increases in cardiac index (0.56 liters/min/m2) and substantial decreases in left ventricular filling pressure (9.9 mm Hg) and systemic vascular resistance (30%) (all p less than 0.01), and these effects persisted for longer than 4 hours. Only 4 patients showed hemodynamic responses with 100 mg of the
drug that were sufficiently marked and long-lasting to merit chronic
therapy, whereas 28 patients had such a response with the 200-mg dose. When 200 mg of
amrinone was administered orally every 8 hours, sustained hemodynamic benefits were seen for 48 hours. However, 16 of 22 patients who received 600 mg of the
drug daily for more than 1 week had intolerable adverse reactions that required
drug withdrawal. In conclusion, hemodynamically effective doses of
amrinone (600 mg/day) cannot be tolerated for long periods by most patients with severe chronic CHF.(ABSTRACT TRUNCATED AT 250 WORDS)