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Impact of CYP2C19 polymorphisms on antiplatelet efficacy of clopidogrel in patients after myocardial infarction
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Abstract
Aim. The aim of this study was to evaluate the complex effects of polymorphisms of the gene encodingthe CYP2C19 enzyme on the antiplatelet efficacy of clopidogrel during follow-up visits.
Material and methods. This study was designed as a prospective, single-centre observational clinical trialwith a one-year follow-up. Data from 178 patients on clopidogrel, taken during follow-up visits, was analysed.
Results. Patients were divided into three groups according to the expected metabolic activity of theCYP2C19enzyme: ‘superior metabolisers’ (681 GG + 806 CT or TT), ‘neutral metabolisers’(681 GG + 806 CC and 681 GA or AA + 806 CT or TT) and ‘inferior metabolisers’ (681 GA or AA + 806 CC).The antiplatelet effect of clopidogrel was strongest in ‘superior metabolisers’ and weakest in ‘inferior metabolisers’,as assessed by adenosine diphosphate (ADP)-induced platelet aggregation and the VASP assay. Comparison of results of ADP-induced platelet aggregation measurements in pairs showed a significant difference (p = 0.03) only between ‘superior metabolisers’ vs. ‘inferior metabolisers’. With the VASP assay,significant differences between ‘superior metabolisers’ and ‘neutral metabolisers’ (p = 0.013), ‘neutralmetabolisers’ and ‘inferior metabolisers’ (p = 0.015), and ‘superior metabolisers’ and ‘inferior metabolisers’(p = 0.00003) were found. No impact on clinical outcome was present. A tendency for an increasingneed for a clopidogrel-to-prasugrel switch was observed with a decrease in CYP2C19 metabolic activity.
Conclusion. Multiple polymorphisms of the gene encoding the CYP2C19 enzyme have a significant impacton the antiplatelet efficacy of clopidogrel during follow-up visits; however, their influence on clinicaloutcome needs further clarification.
Abstract
Aim. The aim of this study was to evaluate the complex effects of polymorphisms of the gene encodingthe CYP2C19 enzyme on the antiplatelet efficacy of clopidogrel during follow-up visits.
Material and methods. This study was designed as a prospective, single-centre observational clinical trialwith a one-year follow-up. Data from 178 patients on clopidogrel, taken during follow-up visits, was analysed.
Results. Patients were divided into three groups according to the expected metabolic activity of theCYP2C19enzyme: ‘superior metabolisers’ (681 GG + 806 CT or TT), ‘neutral metabolisers’(681 GG + 806 CC and 681 GA or AA + 806 CT or TT) and ‘inferior metabolisers’ (681 GA or AA + 806 CC).The antiplatelet effect of clopidogrel was strongest in ‘superior metabolisers’ and weakest in ‘inferior metabolisers’,as assessed by adenosine diphosphate (ADP)-induced platelet aggregation and the VASP assay. Comparison of results of ADP-induced platelet aggregation measurements in pairs showed a significant difference (p = 0.03) only between ‘superior metabolisers’ vs. ‘inferior metabolisers’. With the VASP assay,significant differences between ‘superior metabolisers’ and ‘neutral metabolisers’ (p = 0.013), ‘neutralmetabolisers’ and ‘inferior metabolisers’ (p = 0.015), and ‘superior metabolisers’ and ‘inferior metabolisers’(p = 0.00003) were found. No impact on clinical outcome was present. A tendency for an increasingneed for a clopidogrel-to-prasugrel switch was observed with a decrease in CYP2C19 metabolic activity.
Conclusion. Multiple polymorphisms of the gene encoding the CYP2C19 enzyme have a significant impacton the antiplatelet efficacy of clopidogrel during follow-up visits; however, their influence on clinicaloutcome needs further clarification.
Title
Impact of CYP2C19 polymorphisms on antiplatelet efficacy of clopidogrel in patients after myocardial infarction
Journal
Issue
Article type
Original article
Pages
12-17
Published online
2013-07-11
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681
Article views/downloads
1437
Bibliographic record
Folia Medica Copernicana 2013;1(1):12-17.
Authors
Aldona Kubica
Michał Kasprzak
Karolina Obońska
Marek Koziński
Eliano Pio Navarese
Grzegorz Grześk
Katarzyna Linkowska
Katarzyna Stankowska
Tomasz Fabiszak
Joanna Boinska
Tomasz Grzybowski
Danuta Rość
Jacek Kubica