Abstract | BACKGROUND AND PURPOSE: Studies suggest that smoking affects clopidogrel efficacy. However, whether it influences the association between CYP2C19 genetic variants and clopidogrel efficacy is not clear. METHODS: In total, 2961 patients from the CHANCE trial were involved in this substudy and were successfully genotyped for two single-nucleotide polymorphisms of CYP2C19 (*2 and *3). The Cox proportional risk regression model was used to evaluate the interactions between CYP2C19*2 and CYP2C19*3 carrier status and clopidogrel efficacy stratified by smoking status. RESULTS: There were marginal significant interactions between CYP2C19*2 and CYP2C19*3 allele carrier status and antiplatelet treatment regimen for the risk of recurrent stroke and composite events (P = 0.054, P = 0.051, respectively) amongst smokers, but not in non-smokers. Amongst smokers, clopidogrel plus aspirin decreased the recurrence rate of stroke compared with aspirin alone in non-carriers (3.8% vs. 11.8%, hazard ratio 0.32, 95% confidence interval 0.15-0.65, P = 0.002), but not in carriers. Similar results were also found for the recurrence rate of composite events in smokers. No significant difference was found for hemorrhage events in any group. CONCLUSIONS: Amongst patients with minor stroke or transient ischaemic attack, marginal significant interactions between CYP2C19*2 and CYP2C19*3 allele carrier status and clopidogrel efficacy were found in smokers but not in non-smokers. Amongst smokers, clopidogrel plus aspirin might decrease the recurrence rate of stroke in non-carriers of *2 and *3 alleles of CYP2C19 compared with aspirin alone. However, caution should be taken to interpret our findings in view of several limitations in our study.
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Authors | T Wang, Y Pan, J Lin, R Anand, D Wang, S C Johnston, X Meng, H Li, X Zhao, L Liu, Y Wang, Y Wang, CHANCE investigators |
Journal | European journal of neurology
(Eur J Neurol)
Vol. 26
Issue 9
Pg. 1175-1182
(09 2019)
ISSN: 1468-1331 [Electronic] England |
PMID | 30974489
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | © 2019 EAN. |
Chemical References |
- Platelet Aggregation Inhibitors
- Clopidogrel
- CYP2C19 protein, human
- Cytochrome P-450 CYP2C19
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Topics |
- Aged
- Clopidogrel
(administration & dosage, pharmacology)
- Cytochrome P-450 CYP2C19
(genetics)
- Female
- Humans
- Ischemic Attack, Transient
(drug therapy)
- Male
- Middle Aged
- Outcome Assessment, Health Care
- Pharmacogenomic Variants
- Platelet Aggregation Inhibitors
(administration & dosage, pharmacology)
- Polymorphism, Single Nucleotide
- Smoking
(genetics)
- Stroke
(drug therapy)
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