High frequency of CYP2C19*2 carriers in PCI-treated patients switched over from clopidogrel to prasugrel based on platelet function monitoring

摘要

Among patients undergoing percutaneous coronary intervention (PCI), subjects with high on-clopidogrel treatment platelet reactivity (HCPR) exhibit a high risk for post-procedural thrombotic events including stent thrombosis [1]. Numerous non-genetic and genetic variables were discovered as major factors causing HCPR. Among the genetic variables, the common loss-of-function CYP2C19*2 polymorphism was found to be associated with an attenuated response to clopidogrel [2] and a higher risk for stent thrombosis [3]. However, prior studies suggested that -based on statistical models - this genetic marker may only account for about 5-12% of the observed variability in clopidogrel response [4, 5]. This suggests that a single genetic variant such as CYP2C19*2 may only have little impact on the overall response to clopidogrel treatment and genotyping of this variant may be of limited value in routine clinical practice. The prevalence of CYP2C19*2 as a causative factor for high levels of on-clopidogrel treatment platelet reactivity was never investigated in a clinical scenario where patients are switched over from clopidogrel to prasugrel treatment due to clopidogrel treatment failure. To close this gap of knowledge, the aim of this study was to determine CYP2C19*2 allele carriage in PCI-treated patients initially treated with clopidogrel and switched over to prasugrel therapy due to high levels of platelet reactivity on clopidogrel treatment in a setting of routine platelet function testing.