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Research ArticleINTERVENTIONAL

Association between CYP2C19 Polymorphisms and Outcomes in Cerebral Endovascular Therapy

M. Lin, M. Todaro, J. Chan, L. Churilov, W.S. Zhu, S. Ramdave, P.J. Mitchell, R.J. Dowling, P. Kwan and B. Yan
American Journal of Neuroradiology January 2016, 37 (1) 108-113; DOI: https://doi.org/10.3174/ajnr.A4481
M. Lin
aFrom the Melbourne Brain Centre (M.L., W.S.Z., B.Y.)
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M. Todaro
cNeurology (M.T., P.K., B.Y.), The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia
dDepartment of Medicine (M.T., J.C., S.R., P.K.), University of Melbourne, Melbourne, Victoria, Australia
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J. Chan
dDepartment of Medicine (M.T., J.C., S.R., P.K.), University of Melbourne, Melbourne, Victoria, Australia
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L. Churilov
eFlorey Institute of Neurosciences and Mental Health (L.C.), Melbourne Brain Centre, Heidelberg, Victoria, Australia.
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W.S. Zhu
aFrom the Melbourne Brain Centre (M.L., W.S.Z., B.Y.)
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S. Ramdave
dDepartment of Medicine (M.T., J.C., S.R., P.K.), University of Melbourne, Melbourne, Victoria, Australia
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P.J. Mitchell
bDepartments of Radiology (P.J.M., R.J.D., B.Y.)
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R.J. Dowling
bDepartments of Radiology (P.J.M., R.J.D., B.Y.)
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P. Kwan
cNeurology (M.T., P.K., B.Y.), The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia
dDepartment of Medicine (M.T., J.C., S.R., P.K.), University of Melbourne, Melbourne, Victoria, Australia
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B. Yan
aFrom the Melbourne Brain Centre (M.L., W.S.Z., B.Y.)
bDepartments of Radiology (P.J.M., R.J.D., B.Y.)
cNeurology (M.T., P.K., B.Y.), The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia
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Abstract

BACKGROUND AND PURPOSE: Differing responses to clopidogrel following endovascular treatment of cerebrovascular diseases may increase the risk of vascular complications. CYP2C19 gene polymorphisms influence clopidogrel activity. We aimed to study the clinical impact of CYP2C19 gene polymorphisms in patients undergoing endovascular treatment.

MATERIALS AND METHODS: This was a prospective, longitudinal, observational study. Information on demographics and cerebrovascular status was collected as baseline. Clopidogrel response was tested by the VerifyNow P2Y12 assay. CYP2C19 genotyping was undertaken by polymerase chain reaction–restriction fragment length polymorphism. Three-month follow-up data included vascular complications, mortality, and modified Rankin Scale score. Associations were investigated among CYP2C19 genotypes, clopidogrel responsiveness, and clinical outcomes.

RESULTS: One hundred and eight participants were included. Median age was 56 years (interquartile range, 48.8–65.0 years), and 35 (32.4%) were male. Forty-four participants were classified into group 1 (homozygous CYP2C19*1/*1); 31, into group 2 (25 with CYP2C19*1/*2, two with CYP2C19*1/*3, three with CYP2C19*3/*3, one with CYP2C19*2/*3); 28, into group 3 (24 with CYP2C19*1/*17, four with CYP2C19*17/*17); and 5, into group 4 (CYP2C19*2/*17). A significantly higher proportion of participants in group 3 experienced ischemic events (9 of 28, 32.1%) compared with group 1 (5 of 44, 11.4%; P = .04; odds ratio, 3.7; 95% confidence interval, 1.1–12.6). There was no significant difference in clopidogrel response among the 4 genotype groups.

CONCLUSIONS: Individuals with CYP2C19*17 may have increased risk of ischemic events following endovascular treatment, independent of clopidogrel responsiveness. Larger studies are required to confirm the influence of CYP2C19*17 on clinical outcomes and to understand the mechanisms for increased ischemic events.

ABBREVIATIONS:

IQR
interquartile range
PRU
platelet reactivity unit
  • © 2016 by American Journal of Neuroradiology
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American Journal of Neuroradiology: 37 (1)
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Cite this article
M. Lin, M. Todaro, J. Chan, L. Churilov, W.S. Zhu, S. Ramdave, P.J. Mitchell, R.J. Dowling, P. Kwan, B. Yan
Association between CYP2C19 Polymorphisms and Outcomes in Cerebral Endovascular Therapy
American Journal of Neuroradiology Jan 2016, 37 (1) 108-113; DOI: 10.3174/ajnr.A4481

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Association between CYP2C19 Polymorphisms and Outcomes in Cerebral Endovascular Therapy
M. Lin, M. Todaro, J. Chan, L. Churilov, W.S. Zhu, S. Ramdave, P.J. Mitchell, R.J. Dowling, P. Kwan, B. Yan
American Journal of Neuroradiology Jan 2016, 37 (1) 108-113; DOI: 10.3174/ajnr.A4481
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