Association between CYP2C19 Polymorphisms and Outcomes in Cerebral Endovascular Therapy.
OBJECTIVE
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.


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.
From the Melbourne Brain Centre (M.L., W.S.Z., B.Y.).
M
M
Lin
Neurology (M.T., P.K., B.Y.), The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia Department of Medicine (M.T., J.C., S.R., P.K.), University of Melbourne, Melbourne, Victoria, Australia.
M
M
Todaro
Department of Medicine (M.T., J.C., S.R., P.K.), University of Melbourne, Melbourne, Victoria, Australia.
J
J
Chan
Florey Institute of Neurosciences and Mental Health (L.C.), Melbourne Brain Centre, Heidelberg, Victoria, Australia.
L
L
Churilov
From the Melbourne Brain Centre (M.L., W.S.Z., B.Y.).
W S
WS
Zhu
Department of Medicine (M.T., J.C., S.R., P.K.), University of Melbourne, Melbourne, Victoria, Australia.
S
S
Ramdave
Departments of Radiology (P.J.M., R.J.D., B.Y.).
P J
PJ
Mitchell
Departments of Radiology (P.J.M., R.J.D., B.Y.).
R J
RJ
Dowling
Neurology (M.T., P.K., B.Y.), The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia Department of Medicine (M.T., J.C., S.R., P.K.), University of Melbourne, Melbourne, Victoria, Australia kwanp@unimelb.edu.au bernard.yan@mh.org.au.
P
P
Kwan
From the Melbourne Brain Centre (M.L., W.S.Z., B.Y.) Departments of Radiology (P.J.M., R.J.D., B.Y.) Neurology (M.T., P.K., B.Y.), The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia kwanp@unimelb.edu.au bernard.yan@mh.org.au.
B
B
Yan
D000328:Adult; D000368:Aged; D000483:Alleles; D002545:Brain Ischemia / Q000235:genetics*; D002561:Cerebrovascular Disorders / Q000235:genetics* / Q000628:therapy*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D004621:Embolization, Therapeutic / Q000379:methods; D057510:Endovascular Procedures / Q000379:methods*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine