Does glycoprotein IIIa gene (PlA) polymorphism influence clopidogrel resistance? A study in older patients

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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.

Original languageEnglish
Pages (from-to)345-350
Number of pages6
JournalDrugs and Aging
Volume24
Issue number4
DOIs
Publication statusPublished - 2007

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clopidogrel
Glycoproteins
Genes
Alleles
Aspirin
Platelet Aggregation
Blood Platelets
Hungary
Platelet Aggregation Inhibitors
Secondary Prevention

ASJC Scopus subject areas

  • Pharmacology
  • Geriatrics and Gerontology

Cite this

@article{1c28c6c2269b481585b4a74a76c2114e,
title = "Does glycoprotein IIIa gene (PlA) polymorphism influence clopidogrel resistance? A study in older patients",
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{\circledR} 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.",
author = "E. Papp and V. Havasi and J. Bene and K. Koml{\'o}si and G. Tali{\'a}n and G. Feh{\'e}r and B. Horv{\'a}th and L. Szap{\'a}ry and K. T{\'o}th and B. Melegh",
year = "2007",
doi = "10.2165/00002512-200724040-00006",
language = "English",
volume = "24",
pages = "345--350",
journal = "Drugs and Aging",
issn = "1170-229X",
publisher = "Adis International Ltd",
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TY - JOUR

T1 - Does glycoprotein IIIa gene (PlA) polymorphism influence clopidogrel resistance? A study in older patients

AU - Papp, E.

AU - Havasi, V.

AU - Bene, J.

AU - Komlósi, K.

AU - Talián, G.

AU - Fehér, G.

AU - Horváth, B.

AU - Szapáry, L.

AU - Tóth, K.

AU - Melegh, B.

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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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