ACUTE HEMODYNAMIC INTERACTION OF ASPIRIN AND TICLOPIDINE WITH ENALAPRIL - RESULTS OF A DOUBLE-BLIND, RANDOMIZED COMPARATIVE TRIAL

Background-Coprescription of aspirin and ACE inhibitors is frequent in heart failure caused by coronary artery disease. Negative interaction between aspirin and enalapril has been reported, presumably through i nhibition by aspirin of ACE inhibitor-induced prostaglandin synthesis. Ticlopidine is a potent antiplatelet agent without interaction with p rostaglandin synthesis. Methods and Results-The objective of this stud y was to compare the influence of a coadministration of ticlopidine or aspirin on the hemodynamic effects of an ACE inhibitor (enalapril) in patients with chronic heart failure. Twenty patients with severe hear t failure were enrolled in a double-blind comparative trial and alloca ted to ticlopidine (500 mg daily, 12 patients) or aspirin (325 mg dail y, 8 patients). Hemodynamic evaluation was performed after 7 days of t reatment, every hour for 4 hours after an oral administration of 10 mg of enalapril. Significant reductions in systemic vascular resistance were observed in the ticlopidine group, in contrast to no significant decrease in the aspirin group, A significant (P=0.03) time-by-treatmen t interaction indicated significant aspirin-enalapril drug interaction . Total pulmonary resistance decreased significantly in both groups, w ith no difference between patients assigned to aspirin or ticlopidine. Conclusions-Enalapril reduced systemic vascular resistance more effec tively when given in combination with ticlopidine than with aspirin, I n contrast, the reduction in total pulmonary resistance is similar whe n enalapril is administered in combination with aspirin or ticlopidine , Negative aspirin-enalapril interaction on prostaglandin synthesis pr esumably alters vasodilatation in systemic vessels, whereas prostaglan din-independent actions of ACE inhibition such as pulmonary arterial v asodilatation are maintained.