Rationale, design and population baseline characteristics of the PERFORM Vascular Project: an ancillary study of the 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
PERFORM is exploring the efficacy of terutroban versus aspirin for secondary prevention in patients with a history of ischemic stroke or transient ischemic attacks (TIAs). The PERFORM Vascular Project will evaluate the effect of terutroban on progression of atherosclerosis, as assessed by change in carotid intima-media thickness (CIMT) in a subgroup of patients.
Methods and results
The Vascular Project includes structural (CIMT, carotid plaques) and functional (carotid stiffness) vascular studies in all patients showing at least one carotid plaque at entry. Expected mean follow-up is 36 months. Primary endpoint is rate of change of CIMT. Secondary endpoints include emergent plaques and assessment of carotid stiffness. 1,100 patients are required for 90% statistical power to detect treatment-related CIMT difference of 0.025 mm. The first patient was randomized in April 2006.
The PERFORM Vascular Project will investigate terutroban’s effect on vascular structure and function in patients with a history of ischemic stroke or TIAs.
- Sorbera LA, Serradell N, Bolos J, Bayes M. Terutroban sodium. Prostanoid tp receptor antagonist, antithrombotic agent, antiatherosclerotic agent. Drugs Future. 2006;31:867–73. CrossRef
- Fiessinger JN. S18886, a new specific TP-receptor antagonist, is safe and as effective as aspirin in inhibiting platelet aggregation in patients with peripheral arterial disease. Eur Heart J. 2004;25:573.
- Bousser MG, Amarenco P, Chamorro A, et al. Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) study. Cerebrovasc Dis. 2009;27:509–18. CrossRef
- Bousser MG, Amarenco P, Chamorro A, et al. The Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack (PERFORM) study: baseline characteristics of the population. Cerebrovasc Dis. 2009;27:608–13. CrossRef
- Cheng Y, Austin SC, Rocca B, et al. Role of prostacyclin in the cardiovascular response to thromboxane A2. Science. 2002;296:539–41. CrossRef
- Cayatte AJ, Du Y, Oliver-Krasinski J, Lavielle G, Verbeuren TJ, Cohen RA. The thromboxane receptor antagonist S18886 but not aspirin inhibits atherogenesis in apo E-deficient mice: evidence that eicosanoids other than thromboxane contribute to atherosclerosis. Arterioscler Thromb Vasc Biol. 2000;20:1724–8.
- Egan KM, Wang M, Fries S, et al. Cyclooxygenases, thromboxane, and atherosclerosis: plaque destabilization by cyclooxygenase-2 inhibition combined with thromboxane receptor antagonism. Circulation. 2005;111:334–42. CrossRef
- Viles Gonzalez JF, Fuster V, Corti R, et al. Atherosclerosis regression and TP receptor inhibition: effect of S18886 on plaque size and composition—a magnetic resonance imaging study. Eur Heart J. 2005;26:1557–61. CrossRef
- Worth NF, Berry CL, Thomas AC, Campbell JH. S18886, a selective TP receptor antagonist, inhibits development of atherosclerosis in rabbits. Atherosclerosis. 2005;183:65–73. CrossRef
- Belhassen L, Pelle G, Dubois Rande JL, Adnot S. Improved endothelial function by the thromboxane A2 receptor antagonist S18886 in patients with coronary artery disease treated with aspirin. J Am Coll Cardiol. 2003;41:1198–204. CrossRef
- O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson Jr SK. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med. 1999;340:14–22. CrossRef
- Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation. 1997;96:1432–7.
- Chambless LE, Heiss G, Folsom AR, et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993. Am J Epidemiol. 1997;146:483–94.
- Chambless LE, Folsom AR, Clegg LX, et al. Carotid wall thickness is predictive of incident clinical stroke: the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol. 2000;151:478–87.
- Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation. 2007;115:459–67. CrossRef
- Touboul PJ, Hennerici MG, Meairs S, et al. Mannheim carotid intima-media thickness consensus (2004–2006). An update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006. Cerebrovasc Dis. 2007;23:75–80. CrossRef
- Zureik M, Ducimetiere P, Touboul PJ, et al. Common carotid intima-media thickness predicts occurrence of carotid atherosclerotic plaques: longitudinal results from the Aging Vascular Study (EVA) study. Arterioscler Thromb Vasc Biol. 2000;20:1622–9.
- Amarenco P, Labreuche J, Lavallee P, Touboul PJ. Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke. 2004;35:2902–9. CrossRef
- Kodama M, Yamasaki Y, Sakamoto K, et al. Antiplatelet drugs attenuate progression of carotid intima-media thickness in subjects with type 2 diabetes. Thromb Res. 2000;97:239–45. CrossRef
- Pitt B, Byington RP, Furberg CD, et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators. Circulation. 2000;102:1503–10.
- Crouse III JR, Raichlen JS, Riley WA, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007;297:1344–53. CrossRef
- Liang Q, Wendelhag I, Wikstrand J, Gustavsson T. A multiscale dynamic programming procedure for boundary detection in ultrasonic artery images. IEEE Trans Med Imaging. 2000;19:127–42. CrossRef
- Dogan S, Meijer R, Grobbee DE, et al. Assessment of carotid plaque progression with ultrasound in a low-risk population. Presented at the International Symposium on Atherosclerosis, Boston, Mass, USA. 2009.
- Paini A, Boutouyrie P, Calvet D, Tropeano AI, Laloux B, Laurent S. Carotid and aortic stiffness: determinants of discrepancies. Hypertension. 2006;47:371–6. CrossRef
- Van Bortel LM, Balkestein EJ, van der Heijden-Spek JJ, et al. Non-invasive assessment of local arterial pulse pressure: comparison of applanation tonometry and echo-tracking. J Hypertens. 2001;19:1037–44. CrossRef
- Laurent S, Cockcroft J, Van BL, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27:2588–605. CrossRef
- Rationale, design and population baseline characteristics of the PERFORM Vascular Project: an ancillary study of the 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
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Cardiovascular Drugs and Therapy
Volume 24, Issue 2 , pp 175-180
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Antiatherosclerotic activity
- Antiplatelet agent
- Carotid intima-media thickness
- Ischemic stroke
- Carotid plaque
- Clinical trial
- Industry Sectors
- Author Affiliations
- 1. Department of Neurology, University of Heidelberg, Mannheim, Germany
- 6. University of Heidelberg, Universitätsmedizin Mannheim UMM, Theodor-Kutzer-Ufer, 68135, Mannheim, Germany
- 2. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
- 3. Robertson Centre for Biostatistics, Glasgow, UK
- 4. Department of Pharmacology and INSERM U970, Hôpital Européen Georges Pompidou, Paris, France
- 5. Department of Neurology and Stroke Center, Hôpital Bichat, Paris, France