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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Am+Heart+Assoc
2015 ; 4
(6
): e001652
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CYP2C19 metabolizer status and clopidogrel efficacy in the Secondary Prevention
of Small Subcortical Strokes (SPS3) study
#MMPMID26019129
McDonough CW
; McClure LA
; Mitchell BD
; Gong Y
; Horenstein RB
; Lewis JP
; Field TS
; Talbert RL
; Benavente OR
; Johnson JA
; Shuldiner AR
J Am Heart Assoc
2015[May]; 4
(6
): e001652
PMID26019129
show ga
BACKGROUND: The role of the CYP2C19 genotype on clopidogrel efficacy has been
studied widely, with data suggesting reduced clopidogrel efficacy in
loss-of-function variant carriers taking clopidogrel after percutaneous coronary
intervention; however, data are limited regarding the association between CYP2C19
genetic variants and outcomes in stroke patients. We investigated whether CYP2C19
metabolizer status affects the risk of recurrent stroke or major bleeding in
subcortical stroke patients taking dual antiplatelet therapy with aspirin and
clopidogrel. METHODS AND RESULTS: CYP2C19*2 and CYP2C19*17 were genotyped in 522
patients treated with dual antiplatelet therapy from the Secondary Prevention of
Small Subcortical Strokes (SPS3) study. CYP2C19 metabolizer status was inferred
from genotype, and associations with the risk of recurrent stroke and major
bleeding were assessed in the overall cohort and by race/ethnic group with
logistic regression modeling. In the overall cohort, there were no differences in
outcomes by CYP2C19 metabolizer status (recurrent stroke, odds ratio 1.81 [95% CI
0.76 to 4.30]; major bleeding, odds ratio 0.67 [95% CI 0.22 to 2.03]). In white
participants, those with CYP2C19 intermediate or poor metabolizer status had
higher odds of recurrent stroke (odds ratio 5.19 [95% CI 1.08 to 24.90]) than
those with extensive or ultrarapid metabolizer status, but there was no evidence
of difference in major bleeding. CONCLUSIONS: There were significant differences
in recurrent stroke by CYP2C19 genotype-inferred metabolizer status in white
subcortical stroke patients receiving dual antiplatelet therapy with aspirin and
clopidogrel, consistent with cardiovascular studies on CYP2C19 and clopidogrel;
however, the bleeding risk that led to early termination of the antiplatelet arm
of the SPS3 trial does not appear to be explained by CYP2C19 genotype. This study
was relatively underpowered; therefore, these findings should be interpreted with
caution and warrant replication. CLINICAL TRIAL REGISTRATION: URL:
www.clinicaltrials.gov. Unique identifier: NCT00059306.
|Clopidogrel
[MESH]
|Cytochrome P-450 CYP2C19/*genetics
[MESH]
|Female
[MESH]
|Genotype
[MESH]
|Humans
[MESH]
|Male
[MESH]
|Middle Aged
[MESH]
|Platelet Aggregation Inhibitors/metabolism/*therapeutic use
[MESH]
|Recurrence
[MESH]
|Secondary Prevention/*methods
[MESH]
|Stroke/epidemiology/genetics/*prevention & control
[MESH]
|Ticlopidine/*analogs & derivatives/metabolism/therapeutic use
[MESH]