Hemodynamic action of nicorandil in chronic congestive heart failure

Nicorandil is a new compound that has shown potent vasodilator activities on venous and arterial beds in experimental pharmacology. This study was designed to evaluate the magnitude and the time course of hemodynamic effects of different doses of nicorandil in congestive heart failure. Eleven patients with severe congestive heart failure (New York Heart Association class III or IV), with a cardiac index less than 3 liters/min/m2 and a pulmonary wedge pressure greater than 15 mm Hg were enrolled in the study. Three patients had ischemic dilated cardiomyopathy and 8 had idiopathic dilated cardiomyopathy. Hemodynamic assessments were performed by right-sided cardiac catheterization (Swan-Ganz catheter) with cardiac output determination (thermodilution) at baseline and from 30 minutes to 12 hours after single oral administration of nicorandil; 3 patients were given 40 mg, 6 patients 60 mg, and 2 patients 80 mg. Maximal hemodynamic changes were observed 30 minutes after dosing and remained statistically significant at 3 hours. Thirty minutes after drug administration, pulmonary wedge pressure decreased 34 +/- 6%, cardiac index increased by 55 +/- 13% and diastolic and mean arterial pressures decreased by 15 +/- 3% and 9 +/- 2%, respectively, from baseline values. The decrease in systolic blood pressure was slight (5 +/- 2%) and not statistically significant. Calculated systemic vascular resistances decreased by 36 +/- 6% and heart rate did not significantly change. Nicorandil was well tolerated. Thus, the results of this first study of nicorandil in congestive heart failure demonstrated the unloading action of this compound on the failing heart, leading to an improvement in cardiac function; further investigation of nicorandil in this therapeutic area is needed.