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- Title
Daily administration of the TP receptor antagonist terutroban improved endothelial function in high-cardiovascular-risk patients with atherosclerosis.
- Authors
Lesault, Pierre-François; Boyer, Laurent; Pelle, Gabriel; Covali-Noroc, Ala; Rideau, Dominique; Akakpo, Servais; Teiger, Emmanuel; Dubois-Randé, Jean-Luc; Adnot, Serge
- Abstract
• Terutroban is a selective TP receptor antagonist, i.e. a specific antagonist of the thromboxane A and prostaglandin endoperoxide receptors, shown to improve endothelial function after a single administration in patients with coronary artery disease. • This randomized, double-blind, placebo-controlled trial demonstrates that repeated-dose terutroban for 15 days improves endothelial function and inhibits thromboxane A-induced platelet aggregation in high-cardiovascular-risk patients taking 300 mg of aspirin per day. Terutroban may prove useful for preventing cardiovascular events in such patients. The specific TP receptor antagonist terutroban improves endothelial function after a single dose in patients with coronary artery disease. Our aim was to evaluate the effects and dose dependency of repeated-dose terutroban on endothelial function and platelet aggregation in high-cardiovascular-risk patients with carotid atherosclerosis. We randomly allocated 48 patients taking 300 mg aspirin per day to placebo or to one of three terutroban dosages (2.5, 5 or 10 mg) for 15 days in a double-blind study. Flow-mediated vasodilatation was evaluated before and 2 h after the first oral dose on day 0 and 2 h after the last oral dose on day 14. On day 0 and day 14, all three terutroban dosages improved flow-mediated vasodilatation and abolished platelet aggregation induced by the TP receptor agonist U46619, without changing the aggregation response to ADP or collagen. Terutroban, by chronically improving endothelium-dependent vasodilatation and inhibiting platelet aggregation, may prove useful for preventing cardiovascular events in high-risk patients.
- Subjects
THROMBOXANES; PROSTAGLANDINS; ENDOTHELIUM physiology; ATHEROSCLEROSIS; BLOOD platelet aggregation; VASODILATION; PATIENTS
- Publication
British Journal of Clinical Pharmacology, 2011, Vol 71, Issue 6, p844
- ISSN
0306-5251
- Publication type
Article
- DOI
10.1111/j.1365-2125.2010.03858.x