Influence of smoking on CYP 2C19 genetic variants and clopidogrel efficacy in patients with minor stroke or transient ischaemic attack
| Autor: | T, Wang, Y, Pan, J, Lin, R, Anand, D, Wang, S C, Johnston, X, Meng, H, Li, X, Zhao, L, Liu, Y, Wang |
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| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty Pharmacogenomic Variants CYP2C19 Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Internal medicine Outcome Assessment Health Care Humans Medicine cardiovascular diseases 030212 general & internal medicine Allele Stroke Aged Aspirin business.industry Smoking Hazard ratio Minor stroke Middle Aged medicine.disease Clopidogrel Confidence interval Cytochrome P-450 CYP2C19 Neurology Ischemic Attack Transient Female Neurology (clinical) business Platelet Aggregation Inhibitors 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | European Journal of Neurology. 26:1175-1182 |
| ISSN: | 1468-1331 1351-5101 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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