Daily administration of the TP receptor antagonist terutroban improved endothelial function in high-cardiovascular-risk patients with atherosclerosis.

Abstract

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.

• Authors: Pierre-François Lesault, Laurent Boyer, Gabriel Pelle, Ala Covali-Noroc, Dominique Rideau, Servais Akakpo, Emmanuel Teiger, Jean-Luc Dubois-Randé, Serge Adnot
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 71 Issue 6 Pg. 844-51 (Jun 2011) ISSN: 1365-2125 [Electronic] England
• PMID: 21564160 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.

Chemical References

• Naphthalenes
• Propionates
• Receptors, Thromboxane
• terutroban

Topics

• Adult
• Aged
• Aged, 80 and over
• Atherosclerosis (drug therapy)
• Coronary Artery Disease (prevention & control)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Endothelium, Vascular (drug effects)
• Female
• Humans
• Male
• Middle Aged
• Naphthalenes (administration & dosage, therapeutic use)
• Platelet Aggregation (drug effects)
• Propionates (administration & dosage, therapeutic use)
• Receptors, Thromboxane (administration & dosage, antagonists & inhibitors)
• Treatment Outcome