Risk factors for clopidogrel resistance in patients with ischemic cerebral infarction and the correlation with ABCB1 gene rs1045642 polymorphism.

Jun-Feng Su,Cheng-Yan Li,Xiao-Hui Hu

doi:10.3892/etm.2014.2058

Abstract

The aim of the present study was to examine clopidogrel resistance (CR) in patients with ischemic cerebral infarction and its potential association with a single nucleotide polymorphism (SNP; rs1045642) in the ABCB1 gene. Patients with ischemic cerebral infarction received clopidogrel (75 mg/day) for 7 days and were then subjected to a turbidimetric assay to determine platelet aggregation. Patients were then divided into a CR group and a clopidogrel-sensitive (CS) group. Demographic and clinical data between the two groups were compared. Multivariate logistic regression analysis was performed to determine independent risk factors of CR. PCR products were sequenced to assess ABCB1 rs1045642 SNP genotype and allele frequencies in each group. In total, 303 patients were enrolled in the study; this included 51 CR cases (16.83%) and 252 CS cases (83.17%). Several parameters, including hypertension, diabetes, calcium channel blocker (CCB), β-receptor blocking agent and proton pump inhibitor use, and creatinine, fasting blood glucose, homocysteine (HCY), high-sensitivity C-reactive protein (hs-CRP) and triglyceride levels were significantly higher in the CR group than in the CS group. Diabetes, hs-CRP-increased use of CCBs, and use of β-blockers were found to be independent risk factors for CR. However, ABCB1 gene rs1045642 polymorphism was not found to be an independent risk factor for CR. In conclusion, CR in ischemic stroke patients is associated with several independent risk factors, including diabetes, hs-CRP-increased use of CCBs, and use of β-blockers. However, ABCB1 gene rs1045642 polymorphism has no correlation with CR.

Highlights

Clopidogrel is an anti-platelet agent used to prevent blood clots
Univariate analysis demonstrated that several risk factors associated with ischemic stroke, including hypertension and diabetes, correlated with clopidogrel resistance (CR) (Table I)
It was observed that CR was associated with the administration of various agents, including calcium channel blocker (CCB) (χ2=10.566, P

Summary

Introduction

Clopidogrel is an anti-platelet agent used to prevent blood clots. A number of studies have confirmed the clinical efficacy of clopidogrel as an anti-thrombotic agent, its efficiency in preventing platelet aggregation is not uniform in all patients. Another study reported that in patients treated with clopidogrel, ABCB1 3435C>T polymorphism, T allele carriers and major adverse cardiovascular events (MACE) are all closely associated with risk [11]. These earlier studies focused on coronary heart disease patients, whose disease pathogenesis differs from those with ischemic stroke. The data obtained may help to improve individualized antiplatelet treatment options for the ischemic stroke population and reduce adverse side‐effects

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