TY - JOUR
T1 - Failure of low doses of amrinone to produce sustained hemodynamic improvement in patients with severe chronic congestive heart failure
AU - Packer, Milton
AU - Medina, Norma
AU - Yushak, Madeline
PY - 1984/11/1
Y1 - 1984/11/1
N2 - 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 determine 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 <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 <0.01), and these effects persisted for longer than 4 hours. Only 4 patients showed hemodynamic reponses 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. These observations may explain the ineffectiveness of the drug in controlled clinical trials.
AB - 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 determine 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 <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 <0.01), and these effects persisted for longer than 4 hours. Only 4 patients showed hemodynamic reponses 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. These observations may explain the ineffectiveness of the drug in controlled clinical trials.
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U2 - 10.1016/S0002-9149(84)80138-1
DO - 10.1016/S0002-9149(84)80138-1
M3 - Article
C2 - 6496324
AN - SCOPUS:0021684597
SN - 0002-9149
VL - 54
SP - 1025
EP - 1029
JO - The American journal of cardiology
JF - The American journal of cardiology
IS - 8
ER -