Long-term beneficial effects of endralazine, a new arteriolar vasodilator at rest and during exercise capacity in chronic congestive heart failure.

Hemodynamic measurements were made at rest and during submaximal and maximal exercise in 12 patients with chronic congestive heart failure before and after oral endralazine (EN). After acute assessment, patients received endralazine, twice daily, for a mean of 2.8 months, when hemodynamic measurements were repeated. The drug was withdrawn for 3 to 4 days and subsequently reintroduced. Three patients with greatly elevated pulmonary wedge pressures were assessed after 30 mg of isosorbide dinitrate, which was also chronically administered. Resting mean cardiac and stroke volume indexes increased by 44 and 33%, respectively (p less than 0.01), with concomitant reduction of the systemic resistance. This improvement was maintained on a long-term basis in 8 of the 11 surviving patients. Withdrawal and subsequent reintroduction of EN confirmed that there was worsening of left ventricular dysfunction in the other 3 subjects. Chronic but not acute therapy produced a modest reduction in wedge pressure. At maximal exercise, cardiac and stroke volume indexes increased by 29 and 18%, respectively (p less than 0.01), after EN; the duration of exercise increased in 7 of the 10 subjects after acute therapy and this was maintained on a long-term basis. Mean creatinine clearance increased by 34% (p less than 0.01). The results confirm that EN produces acute and long-term hemodynamic and functional improvement without tolerance in congestive heart failure.