Background: The relationship between cytochrome P450 2C19 (CYP2C19) polymorphisms and clopidogrel efficacy in patients with percutaneous coronary intervention (PCI) has been widely studied. However, the relationship between CYP2C19 polymorphisms and the response to clopidogrel in patients treated for ischemic stroke (IS) remains controversial. What's more, few data address the relevance of CYP2C19 polymorphisms in patients taking clopidogrel for secondary prevention of ischemic stroke. This study investigates whether carrying CYP2C19 loss-of-function (LOF) alleles affects the risk of recurrent stroke in IS patients.
Methods: One hundred twenty-two IS patients were CYP2C19 genotype screened and enrolled in the study from January 2016 to December 2017. Those with stroke recurrence, stroke sequelae, or bleeding diseases were excluded. The remaining 89 patients were divided into the following 2 groups: non-carriers of CYP2C19 LOF alleles (n=38) and carriers (n=51) of CYP2C19 LOF alleles. The variables that could influence the rate of recurrent stroke were assessed in a multivariate analysis to determine the independent risk factors.
Results: The CYP2C19*2 and *3 alleles frequencies among the 122 patients were 31.97% and 4.10%, respectively. Carriers of LOF alleles had a more significant history of hypertension compared with non-carriers [n=43/51 (86.7%) versus n=23/38 (60.5%), P=0.01]. In addition, the inclusion rate of aspirin in discharge medication was significantly higher for carriers than for non-carriers [n=19/51 (37.3%) versus n=5/38 (13.2%), P=0.01]. CYP2C19 LOF alleles were significantly associated with an increased risk of recurrent stroke [odds ratio (OR): 7.586; 95% confidence interval (CI): 1.346-42.770, P=0.022].
Conclusions: CYP2C19 LOF alleles may increase the risk of recurrent IS. The polymorphisms of CYP2C19 may be predictors of a poor functional outcome in patients with recurrent stroke. Instead of clopidogrel, aspirin can be prescribed as a secondary preventative measure against stroke in carriers of CYP2C19 LOF alleles.
Keywords: CYP2C19 LOF allele; CYP2C19 polymorphisms; clopidogrel efficacy; ischemic stroke.