Abstract | BACKGROUND: 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.
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Authors | Caitrin W McDonough, Leslie A McClure, Braxton D Mitchell, Yan Gong, Richard B Horenstein, Joshua P Lewis, Thalia S Field, Robert L Talbert, Oscar R Benavente, Julie A Johnson, Alan R Shuldiner |
Journal | Journal of the American Heart Association
(J Am Heart Assoc)
Vol. 4
Issue 6
Pg. e001652
(May 27 2015)
ISSN: 2047-9980 [Electronic] England |
PMID | 26019129
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
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Copyright | © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. |
Chemical References |
- Platelet Aggregation Inhibitors
- Clopidogrel
- Cytochrome P-450 CYP2C19
- Ticlopidine
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Topics |
- Clopidogrel
- Cytochrome P-450 CYP2C19
(genetics)
- Female
- Genotype
- Humans
- Male
- Middle Aged
- Platelet Aggregation Inhibitors
(metabolism, therapeutic use)
- Recurrence
- Secondary Prevention
(methods)
- Stroke
(epidemiology, genetics, prevention & control)
- Ticlopidine
(analogs & derivatives, metabolism, therapeutic use)
- Treatment Outcome
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