title: Daily administration of the TP receptor antagonist terutroban improved endothelial function in high-cardiovascular-risk patients with atherosclerosis.
abstract: BACKGROUND
  • 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.
  
  
  CONCLUSIONS
  • 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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Terutroban, by chronically improving endothelium-dependent vasodilatation and inhibiting platelet aggregation, may prove useful for preventing cardiovascular events in high-risk patients.
authors.affiliation: INSERM, Unité 955, Université Paris-Est Créteil Val de Marne, Faculté de Médecine, UMR U955, France.
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Lesault
authors.forename: Laurent
authors.initials: L
authors.lastname: Boyer
authors.forename: Gabriel
authors.initials: G
authors.lastname: Pelle
authors.forename: Ala
authors.initials: A
authors.lastname: Covali-Noroc
authors.forename: Dominique
authors.initials: D
authors.lastname: Rideau
authors.forename: Servais
authors.initials: S
authors.lastname: Akakpo
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Teiger
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Dubois-Randé
authors.forename: Serge
authors.initials: S
authors.lastname: Adnot
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000188:drug therapy*; D003324:Coronary Artery Disease / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage* / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects*; D011422:Propionates / Q000008:administration & dosage* / Q000627:therapeutic use; D017482:Receptors, Thromboxane / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D009281:Naphthalenes; D011422:Propionates; D017482:Receptors, Thromboxane; C501362:terutroban