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Related Collections Hemostasis, Thrombosis, and Vascular Biology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2001, Vol. 98, No. 12, pp. 3256-3260 CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes Fiona F. O'Connor, Denis C. Shields, Anthony Fitzgerald, Christopher P. Cannon, Eugene Braunwald, and Desmond J. Fitzgerald From the Departments of Clinical Pharmacology and Epidemiology, and Surgen Ltd, Royal College of Surgeons in Ireland; the Cardiovascular Division, Brigham and Women's Hospital; and Harvard Medical School, Boston, MA. This study examined the influence of the PlA polymorphism of glycoprotein IIIa (GPIIIa) in determining the response to an oral GPIIb/IIIa antagonist, orbofiban, in patients with unstable coronary syndromes. Genotyping for the PlA polymorphism was performed in 1014 patients recruited into the OPUS-TIMI-16 (orbofiban in patients with unstable coronary syndromes-thrombolysis in myocardial infarction 16) trial, in which patients were randomized to low- or high-dose orbofiban or placebo for 1 year. The primary end point (n = 165) was a composite of death, myocardial infarction (MI), recurrent ischemia requiring rehospitalization, urgent revascularization, and stroke. Overall, orbofiban failed to reduce ischemic events when compared with placebo, but increased the rate of bleeding. In the whole population, PlA2 carriers had a significant increase in MI (n = 33) during follow up, with a relative risk (RR) of 2.71 (95% CI, 1.37 to 5.38; P = .004). There was a significant interaction between treatment (placebo and orbofiban) and the PlA polymorphism for bleeding (n = 187; P = .05). Thus, while orbofiban increased bleeding in noncarriers (RR = 1.87, 1.29 to 2.71; P < .001) in a dose-dependent fashion, it did not increase bleeding events in PlA2 carriers (RR = 0.87, 0.46 to 1.64). There was no interaction between treatment (placebo and orbofiban) and the PlA polymorphism for the primary end point (P = .10). However, in the patients receiving orbifiban there was a higher risk of a primary event (RR = 1.55, 1.03 to 2.34; P = .04) and MI (RR 4.27, 1.82 to 10.03; P < .001) in PlA2 carriers compared with noncarriers. In contrast, there was no evidence that PlA2 influenced the rate of recurrent events in placebo-treated patients. In patients presenting with an acute coronary syndrome, the PlA polymorphism of GPIIb/IIIa may explain some of the variance in the response to an oral GPIIb/IIIa antagonist. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Marin, R. Gonzalez-Conejero, P. Capranzano, T. A. Bass, V. Roldan, and D. J. Angiolillo Pharmacogenetics in cardiovascular antithrombotic therapy. J. Am. Coll. Cardiol., September 15, 2009; 54(12): 1041 - 1057. [Abstract] [Full Text] [PDF] S. T. Morozowich, B. S. Donahue, and I. J. Welsby Genetics of coagulation: considerations for cardiac surgery. Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2006; 10(4): 297 - 313. [Abstract] [PDF] A. Lepantalo, K. S Virtanen, J. Heikkila, U. Wartiovaara, and R. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020