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Eur J Neurol. 2019 Apr 11. doi: 10.1111/ene.13962. [Epub ahead of print]

Influence of smoking on CYP2C19 genetic variants and clopidogrel efficacy in patients with minor stroke or transient ischaemic attack.

Author information

1
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
2
China National Clinical Research Center for Neurological Diseases, Beijing, China.
3
Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA.
4
INI Stroke Network, OSF Healthcare System, University of Illinois College of Medicine, Peoria, IL, USA.
5
Dell Medical School, University of Texas at Austin, Austin, TX, USA.

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.

KEYWORDS:

TIA ; CYP2C19; antiplatelet; clopidogrel; minor stroke; smoking

PMID:
30974489
DOI:
10.1111/ene.13962

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