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Efficacy of clopidogrel for stroke depends on CYP2C19 genotype and risk profile

Jie Xu1,2,3,4, Anxin Wang1,2,3,4, Runqi Wangqin5

  • 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Annals of Neurology
|June 26, 2019
PubMed

Insights

Dual antiplatelet therapy (DAT) with clopidogrel plus aspirin shows no overall benefit for minor stroke/transient ischemic attack patients with CYP2C19 loss-of-function alleles. However, high-risk patients with these alleles significantly benefit from DAT.

Area of Science:

  • Neurology
  • Pharmacogenomics
  • Cardiovascular Medicine

Background:

  • Dual antiplatelet therapy (DAT) with clopidogrel and aspirin is recommended for minor stroke (MS) and transient ischemic attack (TIA) patients.
  • The efficacy of DAT may be influenced by genetic factors, specifically CYP2C19 genotype.

Purpose of the Study:

  • To identify patient subgroups who benefit from DAT in MS/TIA.
  • To compare the effectiveness of clopidogrel-aspirin versus aspirin alone in MS/TIA patients stratified by CYP2C19 genotype and risk profiles.

Main Methods:

  • Patients with MS/TIA were stratified based on CYP2C19 loss-of-function allele (LoFA) status and Essen Stroke Risk Score (ESRS) into low (<3) and high (≥3) risk groups.
  • Stroke recurrence at 1 year was the primary outcome, comparing clopidogrel-aspirin therapy against aspirin monotherapy.

Main Results:

  • No significant difference in stroke recurrence was observed between DAT and aspirin alone for overall LoFA carriers (11.2% vs 13.3%).
  • Significant benefits of DAT were found in specific subgroups: LoFA carriers at high risk (HR=0.63), LoFA noncarriers at low risk (HR=0.62), and LoFA noncarriers at high risk (HR=0.52).
  • A significant interaction (p=0.021) was detected between CYP2C19 genotype and risk profile in determining DAT efficacy.

Conclusions:

  • Overall, CYP2C19 LoFA carriers do not appear to benefit from DAT for MS/TIA.
  • High-risk LoFA carriers represent a subgroup that significantly benefits from clopidogrel-aspirin therapy.
  • The effectiveness of clopidogrel in Chinese MS/TIA patients is dependent on both CYP2C19 genotype and clinical risk profile.
Abstract

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