Thromboxane prostaglandin receptor antagonist and carotid atherosclerosis progression in patients with cerebrovascular disease of ischemic origin: a randomized controlled trial

Michiel L Bots; Ian Ford; Suzanne M Lloyd; Stephane Laurent; Pierre J Touboul; Michael G Hennerici; Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin With Terutroban in Patients With a History of Ischemic Stroke or Transient Ischemic Attack Vascular Ultrasound Study Investigators

doi:10.1161/STROKEAHA.114.004775

Thromboxane prostaglandin receptor antagonist and carotid atherosclerosis progression in patients with cerebrovascular disease of ischemic origin: a randomized controlled trial

Stroke. 2014 Aug;45(8):2348-53. doi: 10.1161/STROKEAHA.114.004775. Epub 2014 Jun 24.

Authors

Michiel L Bots¹, Ian Ford², Suzanne M Lloyd², Stephane Laurent², Pierre J Touboul², Michael G Hennerici²; Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin With Terutroban in Patients With a History of Ischemic Stroke or Transient Ischemic Attack Vascular Ultrasound Study Investigators

Collaborators

Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin With Terutroban in Patients With a History of Ischemic Stroke or Transient Ischemic Attack Vascular Ultrasound Study Investigators:
M G Hennerici, M L Bots, I Ford, S Laurent, P J Touboul, C Anderson, G Donnan, T Phan, V Thijs, D Selchen, D Spence, M Bar, P Kanovsky, I Rektor, O Skoda, D Vaclavik, C Lucas, T Rosolacci, P Trouillas, B Griewing, M Hennerici, A Hetzel, W Koehler, J Roether, M Kaps, A Csanyi, L Csiba, Z Kaposzta, J Nikl, G Panczel, E Pongracz, N Szegedi, A Valikovics, C Cappelletti, V Di Piero, P Prati, P M Rossini, M L Bots, L J Kappelle, A Czlonkowska, W Kozubski, A Kuczynska-Zardzewialy, H Kwiecinsky, A V Salgado, D Butko, E Gusev, P Kamchatnov, S Kotov, V Parfenov, V Skvortsova, L Stakhovskaya, B Zvan, J Alvarez Sabin, J Castillo Sanchez, D Jimenez Martinez, J Serena Leal, J M Trejo Gabriel, J Vivancos Mora, R W Baumgartner, L Hirt, K Lees, R MacWalter

Affiliations

¹ 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.
² 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.).

PMID: 25070960
DOI: 10.1161/STROKEAHA.114.004775

Abstract

Background and purpose: 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%.

Clinical trial registration url: http://www.controlled-trials.com. Unique identifier: ISRCTN66157730.

Keywords: atherosclerosis; carotid intima-media thickness; randomized controlled trial.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Atherosclerosis / complications
Atherosclerosis / drug therapy*
Brain Ischemia / complications
Brain Ischemia / drug therapy*
Carotid Artery Diseases / complications
Carotid Artery Diseases / drug therapy*
Carotid Artery, Common
Carotid Intima-Media Thickness
Disease Progression
Female
Humans
Male
Middle Aged
Naphthalenes / therapeutic use*
Propionates / therapeutic use*
Receptors, Thromboxane / therapeutic use*
Treatment Outcome

Substances

Naphthalenes
Propionates
Receptors, Thromboxane
terutroban

Associated data

ISRCTN/ISRCTN66157730