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

Aleksi Tornio1, Rob Flynn2, Steve Morant2

  • 1Division of Molecular & Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK.

Clinical Pharmacology and Therapeutics
|June 28, 2017
PubMed

Insights

Genetic variations in CYP2C19 affect clopidogrel effectiveness, particularly in stroke patients. Carriers of the CYP2C19*2 allele face a higher risk of recurrent arterial thrombo-occlusive events or death.

Area of Science:

  • Pharmacogenetics
  • Cardiovascular Medicine
  • Neurology

Background:

  • Clopidogrel is a widely used antiplatelet medication.
  • Its efficacy is known to be influenced by genetic variations in cytochrome P450 (CYP)2C19.
  • Limited research exists on clopidogrel pharmacogenetics specifically in stroke patients.

Purpose of the Study:

  • To investigate the real-world impact of CYP2C19 genetic variations on clopidogrel efficacy in patients who have experienced an arterial thrombo-occlusive (ATO) event.
  • To specifically assess the risk in patients with ischemic stroke.

Main Methods:

  • Utilized electronic medical records (EMRs) linked to a bioresource for patient data.
  • Included 651 patients hospitalized for an ATO event who later filled clopidogrel prescriptions.
  • Followed patients for 24 months to record recurrent ATO events or death.

Main Results:

  • The primary endpoint (recurrent ATO or death) occurred in 46% of patients.
  • Carriers of the CYP2C19*2 loss-of-function allele showed an increased risk (HR = 1.29).
  • In the ischemic stroke subgroup (n=94), the risk was significantly higher (HR = 2.23), supported by meta-analysis.

Conclusions:

  • Demonstrated the clinical significance of CYP2C19*2 on clopidogrel efficacy using EMR data.
  • The risk associated with CYP2C19*2 may be particularly elevated in the ischemic stroke population.
  • Highlights the importance of pharmacogenetic considerations in antiplatelet therapy for stroke survivors.

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