Background Clopidogrel is a prodrug, metabolised to its active metabolite especially by the CYP2C19 enzyme. The effect of CYP2C19 polymorphisms on clopidogrel efficacy in coronary disease had been widely researched. The clopidogrel label recommends testing the CYP2C19 loss of function alleles before the start of the treatment and the DPWG and CPIC pharmacogenetic dosing guidelines recommend switching clopidogrel in case of carrying the CYP2C19*2 SNP in coronary patients with stent. This remains unstudied in peripheral artery disease (PAD) patients.
Purpose Explore the influence of CYP2C19 genetic polymorphisms on clopidogrel response in PAD patients.
Material and methods Peripheral artery disease patients treated with clopidogrel after percutaneous transluminal angioplasty were recruited. They were tested for carrying the CYP2C19*2, *3 (loss of function (LOF)) and *17 (gain of function (GOF)) allele. The primary endpoint was the occurrence of atherothrombotic ischaemic events, diagnosed by ultrasound imaging, during 12 months’ follow-up. Furthermore, we collected data about clinical parameters (age, sex, ethnicity), co-medication during follow-up, vascular risk factors and surgical parameters.
We tested the association between carrying LOF or GOF alleles and the primary endpoint in a univariate analysis, and multivariate analysis including those clinical parameters previously related to clopidogrel response. OR and HR were calculated and P-values<0.05 were considered statistically significant.
Results Seventy-two patients were recruited, mean age 67.4±9.4 years, 22.2 females and 100% were caucasians. Carrying CYP2C19 LOF alleles was significantly associated with the primary endpoint in the single analysis (OR=4.49; 95% CI: 1.45 to 13.84; p=0.009), in the multivariate analysis (OR=4.89; 95% CI: 1.32 to 12.83; p=0.018). This association remains significant if we perform a survival analysis (HR=4.07; 95% CI: 1.80 to 9.20; p≤0.001). On the other hand, carrying CYP2C19 GOF alleles was not related to the primary endpoint.
Conclusion CYP2C19 LOF polymorphisms show a higher effect on clopidogrel response in PAD patients than that provided in acute coronary syndrome patients. These SNPs may be used as genetic markers of clopidogrel response in PAD patients. Clopidogrel treatment may be guided by CYP2C19 genotyping, although further analysis should be performed.
References and/or acknowledgements Thanks to all the patients participating in this study and all the people working in our hospital who took part in this project.
No conflict of interest.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.