title: Thromboxane prostaglandin receptor antagonist and carotid atherosclerosis progression in patients with cerebrovascular disease of ischemic origin: a randomized controlled trial.
abstract: OBJECTIVE
  Thromboxane prostaglandin receptors have been implicated to be involved in the atherosclerotic process. We assessed whether Terutroban, a thromboxane prostaglandin receptor antagonist, affects the progression of atherosclerosis, as measured by common carotid intima-media thickness and carotid plaques.
  
  
  METHODS
  A substudy was performed among 1141 participants of the aspirin-controlled Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin with Terutroban in Patients with a History of Ischemic Stroke or Transient Ischemic Attack (PERFORM) trial. Common carotid intima-media thickness and carotid plaque occurrence was measured during a 3-year period.
  
  
  RESULTS
  Baseline characteristics did not differ between Terutroban (n=592) and aspirin (n=549) treated patients and were similar as in the main study. Mean study and treatment duration were similar (28 and 25 months, respectively). In the Terutroban group, the annualized rate of change in common carotid intima-media thickness was 0.006 mm per year (95% confidence interval, -0.004 to 0.016) and -0.005 mm per year (95% confidence interval, -0.015 to 0.005) in the aspirin group. There was no statistically significant difference between the groups in the annualized rate of change of common carotid intima-media thickness (0.011 mm per year; 95% confidence interval, -0.003 to 0.025). At 12 months of follow-up, 66% of Terutroban patients had no emergent plaques, 31% had 1 to 2 emergent plaques, and 3% had ≥3 emergent plaques. In the aspirin group, the corresponding percentages were 64%, 32%, and 4%. Over time, there was no statistically significant difference in the number of emergent carotid plaques between treatment modalities (rate ratio, 0.91; 95% confidence interval, 0.77-1.07).
  
  
  CONCLUSIONS
  Compared with aspirin, Terutroban did not beneficially affect progression of carotid atherosclerosis among well-treated patients with a history of ischemic stroke or transient ischemic attacks with an internal carotid stenosis <70%.
  
  
  BACKGROUND
  http://www.controlled-trials.com. Unique identifier: ISRCTN66157730.
authors: From the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom (I.F., S.M.L.); Department of Pharmacology and INSERM U970, Hôpital Européen Georges Pompidou, Paris, France (S.L.); Department of Neurology and Stroke Center, Hôpital Bichat and INSERM U698, Paris, France (P.J.T.); and Department of Neurology, UMM, University of Heidelberg, Mannheim, Germany (M.G.H.). m.l.bots@umcutrecht.nl.
authors: Michiel L
authors: ML
authors: Bots
authors: From the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom (I.F., S.M.L.); Department of Pharmacology and INSERM U970, Hôpital Européen Georges Pompidou, Paris, France (S.L.); Department of Neurology and Stroke Center, Hôpital Bichat and INSERM U698, Paris, France (P.J.T.); and Department of Neurology, UMM, University of Heidelberg, Mannheim, Germany (M.G.H.).
authors: Ian
authors: I
authors: Ford
authors: From the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom (I.F., S.M.L.); Department of Pharmacology and INSERM U970, Hôpital Européen Georges Pompidou, Paris, France (S.L.); Department of Neurology and Stroke Center, Hôpital Bichat and INSERM U698, Paris, France (P.J.T.); and Department of Neurology, UMM, University of Heidelberg, Mannheim, Germany (M.G.H.).
authors: Suzanne M
authors: SM
authors: Lloyd
authors: From the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom (I.F., S.M.L.); Department of Pharmacology and INSERM U970, Hôpital Européen Georges Pompidou, Paris, France (S.L.); Department of Neurology and Stroke Center, Hôpital Bichat and INSERM U698, Paris, France (P.J.T.); and Department of Neurology, UMM, University of Heidelberg, Mannheim, Germany (M.G.H.).
authors: Stephane
authors: S
authors: Laurent
authors: From the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom (I.F., S.M.L.); Department of Pharmacology and INSERM U970, Hôpital Européen Georges Pompidou, Paris, France (S.L.); Department of Neurology and Stroke Center, Hôpital Bichat and INSERM U698, Paris, France (P.J.T.); and Department of Neurology, UMM, University of Heidelberg, Mannheim, Germany (M.G.H.).
authors: Pierre J
authors: PJ
authors: Touboul
authors: From the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands (M.L.B.); Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom (I.F., S.M.L.); Department of Pharmacology and INSERM U970, Hôpital Européen Georges Pompidou, Paris, France (S.L.); Department of Neurology and Stroke Center, Hôpital Bichat and INSERM U698, Paris, France (P.J.T.); and Department of Neurology, UMM, University of Heidelberg, Mannheim, Germany (M.G.H.).
authors: Michael G
authors: MG
authors: Hennerici
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D002340:Carotid Artery Diseases / Q000150:complications / Q000188:drug therapy*; D017536:Carotid Artery, Common; D059168:Carotid Intima-Media Thickness; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D011422:Propionates / Q000627:therapeutic use*; D017482:Receptors, Thromboxane / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D009281:Naphthalenes; D011422:Propionates; D017482:Receptors, Thromboxane; C501362:terutroban
keywords: atherosclerosis; carotid intima-media thickness; randomized controlled trial