Why the study?
Does carriage of the CYP2C19*2 loss-of-function allele increase the risk of recurrent arterial thrombo-occlusive events or death in patients treated with clopidogrel?
Does carriage of the CYP2C19*2 loss-of-function allele increase the risk of recurrent arterial thrombo-occlusive events or death in patients treated with clopidogrel?
CYP2C19*2 loss-of-function allele carriers have a significantly increased risk of recurrent arterial thrombo-occlusive events or death when treated with clopidogrel, particularly following an ischemic stroke.
Supports genotype-guided antiplatelet selection to mitigate recurrent ischemic risk on clopidogrel;.
Clopidogrel efficacy is influenced by genetic variation of cytochrome P450 (CYP)2C19, however, few studies have considered patients who have a stroke. We used electronic medical records (EMRs) linked to a bioresource to examine real-world implications of clopidogrel pharmacogenetics in stroke. Patients hospitalized for any arterial thrombo-occlusive (ATO) event who subsequently redeemed clopidogrel prescriptions in the community were entered into the study (n = 651). During 24-month follow-up, the primary endpoint of recurrent ATO or death occurred in 299 patients (46%). CYP2C19*2 loss-of-function allele carriers had an increased risk (hazard ratio (HR) = 1.29; 95% confidence interval (CI) = 1.04-1.59; P = 0.019). In the ischemic stroke subgroup (n = 94), the estimate of risk was greater (HR = 2.23; 95% CI = 1.17-4.24; P = 0.015), which was further supported by a meta-analysis of available studies. In conclusion, we have demonstrated the clinical impact of CYP2C19*2 on clopidogrel efficacy using a purely EMR approach. This suggests that the risk in the ischemic stroke population may be particularly high.
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Tornio et al. (2017) studied this question.
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