Does Glycoprotein IIIa Gene(Pl A ) Polymorphism Influence Clopidogrel Resistance?
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Drugs Aging 2007; 24 (4): 345-350 1170-229X/07/0004-0345/$44.95/0 © 2007 Adis Data Information BV. All rights reserved.
Does Glycoprotein IIIa Gene (PlA) Polymorphism Influence Clopidogrel Resistance? A Study in Older Patients Elod Papp,1 Viktoria Havasi,2 Judit Bene,2,3 Katalin Komlosi,2 Gabor Talian,2 Gergely Feher,1 Beata Horvath,1 Laszlo Szapary,4 Kalman Toth1 and Bela Melegh2 1 2 3 4
First Department of Medicine, School of Medicine, University of Pecs, Pecs, Hungary Department of Medical Genetics and Child Development, School of Medicine, University of Pecs, Pecs, Hungary Hungarian Academy of Sciences Clinical Genetic Research Group, Pecs, Hungary Department of Neurology, School of Medicine, University of Pecs, Pecs, Hungary
Abstract
Background: Clopidogrel is a potent antiplatelet drug used for secondary prevention after ischaemic cardiovascular or cerebrovascular events. In patients with aspirin (acetylsalicylic acid) intolerance or resistance, it is used as monotherapy. Recent data report that PlA polymorphism of the glycoprotein IIIa gene may account for differences in aspirin-induced antiplatelet effects. An increased degree of platelet reactivity was also reported in PlA2 carriers compared with PlA1/A1 patients after administration of a clopidogrel 300mg loading dose. Objectives: The aim of this study was to assess the modulatory effect of the PlA2 allele on platelet aggregation in patients taking long-term clopidogrel. Methods: The prevalence of the PlA2 allele was assessed in 38 (21 males, 17 females; mean age 63 ± 13 years) clopidogrel-resistant and 59 (26 males, 33 females; mean age 63 ± 11 years) clopidogrel-responsive patients. The polymerase chain reaction-restriction fragment length polymorphism method was utilised to evaluate PlA polymorphism. A Carat TX4® optical platelet aggregometer (Carat Diagnostics Ltd, Budapest, Hungary) was used to measure 5 and 10 μmol/L adenosine diphosphate-induced platelet aggregation. Results: Significantly more patients were taking combination antiplatelet therapy in the clopidogrel-resistant group than in the clopidogrel-responsive group (50% vs 30%, respectively). The prevalence of the PlA2 allele did not differ significantly between the two groups (0.09 vs 0.13), even after adjustment for combination therapy and various risk factors. Conclusions: Our results show that carriers of the PlA2 allele do not have an increased risk of clopidogrel resistance. These findings and data from our previous studies suggest that patients with a PlA2 allele homozygosity may benefit from antiplatelet therapy based on clopidogrel rather than aspirin.
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The essential role of platelets in the pathogenesis of arterial thrombosis is well established. Consequently, platelets represent a major target for therapeutic interventions aimed at decreasing the incidence and severity of cardiovascular and cerebrovascular events in patients at risk. There are three groups of agents that inhibit platelet function: (i) cyclo-oxygenase inhibitors, such as aspirin (acetylsalicylic acid); (i
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