Acute hemodynamic response to low dose enoximone (MDL 17,043): an oral dose-range study

Abstract

The efficacy of low dose oral enoximone (MDL 17,043) was evaluated in the treatment of congestive heart failure (CHF). Fourteen male patients with stable, moderately severe CHF (New York Heart Association functional class II or III) and mean left ventricular ejection fraction of 0.21 +/- 0.02 were randomized to receive 50, 75, 100, 150 or 200 mg of enoximone (mean dose 1.46 +/- 0.16 mg/kg). Hemodynamic data were measured before and during the first 24 hours of therapy. An oral dose was given in the first 24 hours, and then every 8 hours. Acute administration of enoximone resulted in significant improvement in cardiac index (2.07 +/- 0.18 to 2.36 +/- 0.16 liters/min/m2, p less than 0.05), mean pulmonary arterial pressure (35 +/- 4 to 30 +/- 4 mm Hg, p less than 0.02), mean pulmonary artery wedge pressure (22 +/- 3 to 18 +/- 2 mm Hg, p less than 0.05) and systemic vascular resistance (1,712 +/- 148 to 1,384 +/- 82 dynes s cm-5, p less than 0.02). Neither hypotension nor tachycardia was observed. Although there was a trend toward a dose-response relation, hemodynamic responses to doses less than 1.5 mg/kg and greater than 1.5 mg/kg were not significantly different. Clinical symptoms improved with long-term therapy, but left ventricular ejection fraction and exercise treadmill time did not change. In patients with moderate and severe CHF, low doses of enoximone result in significant acute hemodynamic improvement.