Amrinone in the treatment of chronic cardiac failure

Abstract

The efficacy and safety of oral amrinone were examined in 17 patients with moderately severe to severe heart failure that was refractory to standard medical therapy and vasodilators. The short-term and 28 week response to open amrinone therapy was assessed first, followed by a placebo-controlled, double-blind withdrawal study of two 13 week stages in nine patients. Rest and exercise ventricular function were determined before and after 32 hours of amrinone; aerobic capacity was serially assessed. After 2 hours, 1.64 mg/kg amrinone produced a 40% (p less than 0.001) increase in cardiac output and a 32% (p less than 0.02) decrease in pulmonary wedge pressure without altering heart rate or blood pressure. The exercise cardiac index-wedge pressure curve obtained 32 hours after the first oral dose was significantly shifted (p less than 0.05) above control values. A sustained improvement in maximal oxygen uptake was noted during long-term open amrinone therapy. Subsequently, seven of the patients randomized to placebo therapy had a significant deterioration of symptoms or exercise tolerance, or both. After 4 weeks of readministration of amrinone, clinical stability was once again established and exercise tolerance was improved by Weeks 8 to 16. Adverse effects of thrombocytopenia (one patient) and hepatic dysfunction (one patient) attributable to amrinone were observed. It is concluded that amrinone is effective in the long-term treatment of chronic cardiac failure.

Hemodynamic and clinical limitations of long-term inotropic therapy with amrinone in patients with severe chronic heart failure.

“…The failure of amrinone to produce sustained improvement in cardiac performance in our patients with heart failure may explain why patients failed to improve clinically with amrinone in our study and in the experience of other investigators who have evaluated the drug in controlled trials. '7 19 Furthermore, the decline in cardiac performance that we observed upon withdrawal of amrinone confirms previous reports of hemodynamic and clinical deterioration after discontinuation of the drug.23 24 cardioactive agent cannot be used to indicate that the drug was beneficial in the treatment of congestive heart failure.…”

“…In the eight patients who 24 hr of initiation of amrinone therapy. All four patients were successfully resuscitated, but three experienced irreversible neurologic sequelae during the arrhythmia, which eventually led to their deaths; the remaining patient recovered completely, and after amrinone was withdrawn did not have further symptomatic arrhythmias during the following 6 months.…”

“…23 24 Hence, it remains unclear why a drug that produces short-term hemodynamic benefits and to which tolerance does not appear to develop fails to produce long-term clinical improvement. To address this question directly, we evaluated the short-and long-term hemodynamic and clinical responses to amrinone in a large series of patients with severe chronic heart failure, using a study design we have successfully employed to demonstrate the efficacy (and lack of efficacy) of vasodilating drugs .2>22…”

Cardiopulmonary Exercise Testing in Clinical Practice

“…In using the Vo,max measurement we have found that some drugs have improved a pa tient's effort tolerance [10][11][12] while others have not [8]. In those cases where an im provement in aerobic capacity was noted, this response coincided with the patient's reported enhanced effort tolerance to daily living.…”

Clinical Use of Inotropic Therapy for Heart Failure: Looking Backward or Forward? Part I: Inotropic Infusions During Hospitalization

“…44 Subsequent experience also described prolonged improvement after brief therapy with phosphodiesterase inhibitors. 45 These studies have not been repeated in the context of current therapies for heart failure, such as the availability of metolazone to facilitate resolution of volume overload. This rate of clinical improvement is similar to that observed with the vasodilator nesiritide.…”