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Potential Usefulness of Clopidogrel Pharmacogenetics in Cerebral Endovascular Procedures and Carotid Artery Stenting

Jorge Duconge1, Dagmar F Hernandez-Suarez2

  • 1Department of Pharmaceutical Sciences, University of Puerto Rico Medical Sciences Campus, School of Pharmacy, Room 325-14, PO Box 365067; San Juan, PR 00936-5067, United States.

Current Clinical Pharmacology
|March 2, 2017
PubMed

Insights

CYP2C19 genetic variations impact clopidogrel response in carotid artery stenting (CAS). Loss-of-function alleles increase thrombosis risk, while gain-of-function alleles may raise ischemic event risk independently. Further research is needed.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacogenetics
  • Interventional Neurology

Background:

  • Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel shows inadequate response in 5-30% of PCI patients, rising to 66% in neurointerventions.
  • Clopidogrel resistance is a primary cause of DAPT failure, with clinical significance of CYP2C19 genotypes in neurointerventional procedures or CAS remaining unknown.

Purpose of the Study:

  • To update knowledge on the pharmacogenetic basis of poor clopidogrel responsiveness in patients undergoing CAS and endovascular interventions.
  • To explore the utility of genotyping in reducing procedure-related thrombosis and ischemic complications.

Main Methods:

  • A literature search was conducted across three databases for pharmacogenetic studies related to cerebral endovascular interventions and CAS.
  • Relevant pharmacogenetic biomarkers, particularly CYP2C19 polymorphisms, were investigated.

Main Results:

  • The review analyzed 7 papers involving 3 CYP2C19 polymorphisms and 442 subjects.
  • Loss-of-function CYP2C19 polymorphisms (CYP2C19*2, *3) are associated with increased risk of thromboembolic complications, including stent thrombosis, after neurointerventional procedures.
  • The gain-of-function CYP2C19*17 allele may increase ischemic event risk post-endovascular treatment, irrespective of clopidogrel responsiveness.

Conclusions:

  • Current studies on CYP2C19 polymorphisms and antiplatelet response in CAS and cerebrovascular disease are limited.
  • Further validation in large multicenter studies is necessary to confirm these findings.
  • This review highlights the importance of CYP2C19 genotyping in antiplatelet therapy for cerebral endovascular procedures and CAS.
Abstract

Keywords:
CYP2C19Clopidogrelcarotid artery stentingcerebral endovascular proceduresischemic strokepharmacogenetics

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