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Dual therapy with clopidogrel and aspirin prevents early neurological deterioration in ischemic stroke patients carrying CYP2C19*2 reduced-function alleles

  • Pharmacoeconomics
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European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To investigate the associations between CYP2C19 genotypes and early neurological deterioration (END), and to carry out a stratified analysis of the effectiveness of clopidogrel alone and dual antiplatelet therapy with clopidogrel and aspirin for prevention of END according to CYP2C19 genotypes in ischemic stroke (IS) patients.

Methods

This was a prospective, observational, two-center study. A total of 375 acute IS patients were enrolled. Platelet aggregation was measured before and after the 7- to 10-day treatment. Clopidogrel resistance (CR) was assessed by adenosine diphosphate-induced platelet aggregation. CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893) genotypes were examined using mass spectrometry. The primary outcome was END during the 10 days after admission.

Results

Among the 375 patients, 144 patients received clopidogrel alone, 231 patients took clopidogrel plus aspirin, 153 patients (40.8%) had CR, 95 patients (25.3%) experienced END. Patients carrying CYP2C19*2 AG/AA (CYP2C19*2 reduced-function alleles) and CR were associated with a higher risk for END, and dual antiplatelet therapy was associated with a lower risk for END. Stratified analyses revealed that there was no significant difference in the incidence of END between patients not carryingCYP2C19*2 reduced-function alleles who received clopidogrel plus aspirin and those who received clopidogrel alone. However, dual antiplatelet therapy was more effective at reducing END and inhibiting platelet aggregation than clopidogrel alone for carriers of at least one CYP2C19*2 reduced-function allele.

Conclusions

The frequency of END was very high after acute IS in the Chinese population. Dual therapy with clopidogrel and aspirin may be adequate for patients carrying CYP2C19*2 reduced-function alleles. Genetic testing may be useful to guide personalized and precise antiplatelet therapy.

Clinical trial registration information

The study described here is registered at http://www.chictr.org/ (unique Identifier: ChiCTR-OCH-14004724).

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Funding

This study was supported in part by grants from the Deyang City Science and Technology Research Foundation (Grant No. 2014SZ035) and the Scientific Research Foundation of Sichuan Provincial Health Department (Grant No. 140025).

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Author notes

  1. Zhao Han and Chun Wang contributed equally to this work

Authors and Affiliations

  1. Department of Neurology, Third Affiliated Hospital of Wenzhou Medical University, Ruian, 325200, Zhejiang, China

    Jing Lin, Zhenxiao Chai, Qiang Zhou & Ruyue Huang

  2. Department of Neurology, Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China

    Zhao Han

  3. Department of Neurology, People’s Hospital of Deyang City, Deyang, 618000, Sichuan, China

    Chun Wang & Xingyang Yi

Authors
  1. Jing Lin
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  2. Zhao Han
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  5. Zhenxiao Chai
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Corresponding authors

Correspondence to Zhao Han or Chun Wang.

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The authors declare that they have no conflicts of interest.

Ethical approval

The study was approved by the Ethics Committees of the People’s Hospital of Deyang City and The Third Affiliated Hospital of Wenzhou Medical College, and is in accordance with the principles stated in the Declaration of Helsinki.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Lin, J., Han, Z., Wang, C. et al. Dual therapy with clopidogrel and aspirin prevents early neurological deterioration in ischemic stroke patients carrying CYP2C19*2 reduced-function alleles. Eur J Clin Pharmacol 74, 1131–1140 (2018). https://doi.org/10.1007/s00228-018-2468-7

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  • DOI: https://doi.org/10.1007/s00228-018-2468-7

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