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Daily administration of the TP receptor antagonist terutroban improved endothelial function in high‐cardiovascular‐risk patients with atherosclerosis
Author(s) -
Lesault PierreFrançois,
Boyer Laurent,
Pelle Gabriel,
CovaliNoroc Ala,
Rideau Dominique,
Akakpo Servais,
Teiger Emmanuel,
DuboisRandé JeanLuc,
Adnot Serge
Publication year - 2011
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2010.03858.x
Subject(s) - medicine , thromboxane , aspirin , antagonist , receptor antagonist , placebo , thromboxane a2 , agonist , pharmacology , vasodilation , thromboxane receptor , platelet , receptor , pathology , alternative medicine
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Terutroban is a selective TP receptor antagonist, i.e. a specific antagonist of the thromboxane A 2 and prostaglandin endoperoxide receptors, shown to improve endothelial function after a single administration in patients with coronary artery disease. WHAT THIS STUDY ADDS • This randomized, double‐blind, placebo‐controlled trial demonstrates that repeated‐dose terutroban for 15 days improves endothelial function and inhibits thromboxane A 2 ‐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. AIMS 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. METHODS 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. RESULTS 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. CONCLUSION Terutroban, by chronically improving endothelium‐dependent vasodilatation and inhibiting platelet aggregation, may prove useful for preventing cardiovascular events in high‐risk patients.