A1 Refereed original research article in a scientific journal
Investigating Real-World Clopidogrel Pharmacogenetics in Stroke Using a Bioresource Linked to Electronic Medical Records
Authors: Tornio A, Flynn R, Morant S, Velten E, Palmer CNA, MacDonald TM, Doney ASF
Publisher: WILEY
Publication year: 2018
Journal: Clinical Pharmacology and Therapeutics
Journal name in source: CLINICAL PHARMACOLOGY & THERAPEUTICS
Journal acronym: CLIN PHARMACOL THER
Volume: 103
Issue: 2
First page : 281
Last page: 286
Number of pages: 6
ISSN: 0009-9236
DOI: https://doi.org/10.1002/cpt.780
Abstract
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.
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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