title: Effect of the thromboxane prostaglandin receptor antagonist terutroban on arterial thrombogenesis after repeated administration in patients treated for the prevention of ischemic stroke.
abstract: BACKGROUND
  The antithrombotic, antiplatelet and endothelial activity of terutroban, a specific thromboxane prostaglandin receptor antagonist, was assessed in patients previously treated with aspirin for the prevention of ischemic stroke.
  
  
  METHODS
  This double-blind, parallel-group, 10-day study included 48 patients (age = 70.5 +/- 9.5 years) with cerebral ischemic event and/or carotid stenosis in 4 groups: terutroban 10 mg/day (n = 13), aspirin 300 mg/day (n = 12), terutroban 10 mg/day + aspirin 300 mg/day (n = 11) or clopidogrel 75 mg/day + aspirin 300 mg/day (n = 12). The measurements included parameters from an ex vivo model of thrombosis, platelet aggregation in platelet-rich plasma and plasma biomarkers of endothelial/platelet activation.
  
  
  RESULTS
  Between days 0 and 10, the mean cross-sectional surface of dense thrombus significantly decreased with terutroban (58%, p = 0.001), terutroban + aspirin (63%, p = 0.005) and clopidogrel + aspirin (61%, p < 0.05). On day 10, the value for terutroban was significantly lower than that for aspirin (p < 0.01) and was comparable to the dual therapy terutroban + aspirin or clopidogrel + aspirin. Similar results were found for total thrombus surface and platelet adhesion. Platelet aggregation induced by the specific thromboxane prostaglandin receptor agonist U46619 was almost completely inhibited on day 10 in both terutroban groups but not in the others. As regards markers of endothelial/platelet activation or lesions, thrombomodulin significantly increased and plasma soluble P selectin significantly decreased by day 10 in both terutroban groups, whereas the von Willebrand factor did not change significantly. Terutroban was found to be safe and well TOLERATED.
  
  
  CONCLUSIONS
  Terutroban has demonstrated an antithrombotic activity that is superior to aspirin and similar to clopidogrel + aspirin; it induces a significant in vivo reduction in endothelial/platelet activation.
authors.affiliation: Institut des Vaisseaux et du Sang, Hôpital Lariboisière AH-HP and Université Paris 7, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Bal Dit Sollier
authors.forename: I
authors.initials: I
authors.lastname: Crassard
authors.forename: G
authors.initials: G
authors.lastname: Simoneau
authors.forename: J-F
authors.initials: JF
authors.lastname: Bergmann
authors.forename: M G
authors.initials: MG
authors.lastname: Bousser
authors.forename: L
authors.initials: L
authors.lastname: Drouet
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers; D002545:Brain Ischemia / Q000517:prevention & control*; D000077144:Clopidogrel; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D020767:Intracranial Thrombosis / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000009:adverse effects / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011422:Propionates / Q000009:adverse effects / Q000627:therapeutic use*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D020521:Stroke / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D009281:Naphthalenes; D010975:Platelet Aggregation Inhibitors; D011422:Propionates; D017482:Receptors, Thromboxane; C501362:terutroban; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin