Investigating Real-World Clopidogrel Pharmacogenetics in Stroke Using a Bioresource Linked to Electronic Medical Records

TY - JOUR

T1 - Investigating Real-World Clopidogrel Pharmacogenetics in Stroke Using a Bioresource Linked to Electronic Medical Records

AU - Tornio, Aleksi

AU - Flynn, Rob

AU - Morant, Steve

AU - Velten, Elena

AU - Palmer, Colin N. A.

AU - MacDonald, Thomas M.

AU - Doney, Alex S. F.

N1 - A.T. was supported by a Fellowship grant from Sigrid Jusélius Foundation (Helsinki, Finland)

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Clopidogrel efficacy is influenced by genetic variation of CYP2C19, however few studies have considered stroke patients. We used electronic medical records (EMR) linked to a bioresource to examine real-world implications of clopidogrel pharmacogenetics in stroke. Patients hospitalized for any arterial thrombo-occlusive event (ATO) who subsequently redeemed clopidogrel prescriptions in the community were entered into the study (n=651). During 24 months follow-up the primary endpoint of recurrent ATO or death occurred in 299 (46%) patients. CYP2C19*2 loss-of-function allele carriers had an increased risk, hazard ratio (HR) 1.29 (95% confidence interval 1.04-1.59, P=0.019). In the ischemic stroke subgroup (n=94) the estimate of risk was greater (HR 2.23, 95% confidence interval 1.17-4.24, P=0.015) 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.

AB - Clopidogrel efficacy is influenced by genetic variation of CYP2C19, however few studies have considered stroke patients. We used electronic medical records (EMR) linked to a bioresource to examine real-world implications of clopidogrel pharmacogenetics in stroke. Patients hospitalized for any arterial thrombo-occlusive event (ATO) who subsequently redeemed clopidogrel prescriptions in the community were entered into the study (n=651). During 24 months follow-up the primary endpoint of recurrent ATO or death occurred in 299 (46%) patients. CYP2C19*2 loss-of-function allele carriers had an increased risk, hazard ratio (HR) 1.29 (95% confidence interval 1.04-1.59, P=0.019). In the ischemic stroke subgroup (n=94) the estimate of risk was greater (HR 2.23, 95% confidence interval 1.17-4.24, P=0.015) 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.

KW - Clopidogrel

KW - CYP2C19

KW - Electronic medical records

KW - Pharmacogenetic

KW - Stroke

U2 - 10.1002/cpt.780

DO - 10.1002/cpt.780

M3 - Article

C2 - 28653333

SN - 0009-9236

VL - 103

SP - 281

EP - 286

JO - Clinical Pharmacology & Therapeutics

JF - Clinical Pharmacology & Therapeutics

IS - 2

ER -