Acute hemodynamic effects of endralazine: a new vasodilator for chronic refractory congestive heart failure

Invasive hemodynamic measurements were made in 10 supine patients with chronic refractory congestive heart failure (CHF) due to ischemic heart disease or cardiomyopathy before and after oral administration of a new arteriolar vasodilator, endralazine. In 9 patients, a 10 mg dose of endralazine produced maximal increases in cardiac and stroke volume indexes of 56 and 41%, respectively, with a 45% reduction in total systemic resistance. After a 5 mg dose of endralazine, cardiac index increased maximally by 38% and stroke volume index by 34%, with a 31% decrease in total systemic resistance. Mean arterial pressure decreased 11 +/- 4 mm Hg (mean +/- standard error of mean) with the 5 mg dose and 17 +/- 5 mm Hg after the 10 mg dose. There were no significant changes in the right atrial, pulmonary arterial, or pulmonary capillary wedge pressures. After administration of a single dose of endralazine, statistically significant hemodynamic changes were observed from 1 to 8 hours with peak responses at 3 to 4 hours. These observations suggest that endralazine has hemodynamic properties similar to those of its structural analog, hydralazine. However, endralazine metabolism is largely independent of the patients' acetylator status, and no cases of systemic lupus erythematosus have been reported after long-term oral administration. These findings suggest that endralazine may be an efficacious drug that is potentially safer than hydralazine in the treatment of chronic CHF.