From the Department of Cardiology, Cochin Hospital, René Descartes
University, Paris, France.
Correspondence to Christian Spaulding, MD, Department of Cardiology, Cochin Hospital, René Descartes University, 27 rue du Fg St Jacques 75014 Paris, France. E-mail christian.spaulding{at}cch.ap-hop-paris.fr
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 inhibition by
aspirin of ACE inhibitor–induced prostaglandin
synthesis. Ticlopidine is a potent antiplatelet agent without
interaction with prostaglandin synthesis.
Methods and Results—The objective of this study 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 heart failure were enrolled in a double-blind comparative
trial and allocated to ticlopidine (500 mg daily, 12 patients) or
aspirin (325 mg daily, 8 patients). Hemodynamic
evaluation was performed after 7 days of treatment, 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-treatment
interaction indicated significant aspirin-enalapril drug interaction.
Total pulmonary resistance decreased significantly in both
groups, with no difference between patients assigned to aspirin or
ticlopidine.
Conclusions—Enalapril reduced systemic vascular resistance more
effectively when given in combination with ticlopidine than with
aspirin. In contrast, the reduction in total pulmonary
resistance is similar when enalapril is administered in combination
with aspirin or ticlopidine. Negative aspirin-enalapril interaction on
prostaglandin synthesis presumably alters vasodilatation in
systemic vessels, whereas prostaglandin-independent actions
of ACE inhibition such as pulmonary arterial
vasodilatation are maintained.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Acute Hemodynamic Interaction of Aspirin and Ticlopidine With Enalapril
Results of a Double-Blind, Randomized Comparative Trial
Key Words: aspirin • angiotensin • coronary disease • heart failure • prostaglandins
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