Clopidogrel and CYP2C19 gene

CYP2C19 gene and clopidogrel

• large variability in anti-platelet effects in clopidogrel-treated patients after PCI
  • this is partly due to genetic variations in the CYP2C19 gene (1)
    
    
• carriers of a CYP2C19*2 or *3 loss-of-function (LoF) allele are at higher risk for high platelet reactivity when treated with clopidogrel
  
  
• patients who carry a CYP2C19*17 gain-of-function (GoF) allele might have better efficacy of clopidogrel and a possibly higher risk for bleeding with clopidogrel compared to non-carriers of the variant (2)
  
  
• prespecified subanalysis of the POPular Genetics trial assessed the effect of the CYP2C19*17 GoF allele in clopidogrel-treated patients and safety and efficacy of clopidogrel in patients without a CYP2C19*2 or *3 LoF allele compared to patients who received treatment of ticagrelor or prasugrel irrespective of their genotype
  • showed that treatment with clopidogrel was associated with less bleeding without an increase in thrombotic outcomes after PCI in STEMI patients without a CYP2C19*2 or *3 LoF allele, compared to patients with standard ticagrelor or prasugrel treatment. No significant differences in thrombotic or bleeding outcomes were found with use of clopidogrel in carriers of a CYP2C19*17 allele compared to patients with wild-type alleles

Reference:

1. Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, Ruven HJ, Bal ET, Deneer VH, Harmsze AM, van der Heyden JA, Rensing BJ, et al. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA. 2010;303:754-762. doi:10.1001/jama.2010.181
2. Li Y, Tang HL, Hu YF, Xie HG. The gain-of-function variant allele CYP2C19*17: a double-edged sword between thrombosis and bleeding in clopidogrel treated patients. J Thromb Haemost. 2012;10:199-206. doi:10.1111/j.1538-7836.2011.04570.x
3. Claassens DMF, Bergmeijer TO, Vos GJA, et al. Clopidogrel Versus Ticagrelor or Prasugrel After Primary Percutaneous Coronary Intervention According to CYP2C19 Genotype: A POPular Genetics Subanalysis. Circ Cardiovasc Interv. 2021 doi:0.1161/CIRCINTERVENTIONS.120.009434