title: Potential Usefulness of Clopidogrel Pharmacogenetics in Cerebral Endovascular Procedures and Carotid Artery Stenting.
abstract: Previous reports have shown inadequate response to dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in 5-30% of patients undergoing percutaneous coronary interventions (PCI), due mostly to clopidogrel resistance. This prevalence increases up to 66% in patients undergoing neurointerventional procedures. However, clinical significance of CYP2C19 genotypes in neurointerventional procedures or carotid artery stenting (CAS) is unknown.
  
  
  
  The purpose of this review is to update our current knowledge and understanding of the pharmacogenetic basis for poor clopidogrel responsiveness in patients undergoing CAS and endovascular interventions as well as to explore usefulness of genotyping to reduce the rate of procedure-related thrombosis that results in ischemic complications.
  
  
  
  A literature search for pharmacogenetic studies in cerebral endovascular interventions and CAS was conducted on three databases using a list of the most relevant pharmacogenetic biomarkers.
  
  
  
  The review included 7 papers involving 3 genetic polymorphisms on CYP2C19 and 442 subjects. Patients harboring at least one loss-of-function CYP2C19 polymorphism (e.g., CYP2C19*2 and *3) are at an increased risk of thromboembolic complications such as stent thrombosis following neurointerventional procedures. Notably, patients who carry the gain-of-function CYP2C19*17 allele may have increased risk of ischemic events following endovascular treatment, independent of clopidogrel responsiveness.
  
  
  
  Studies assessing the influence of CYP2C19 polymorphisms on high on-treatment platelet reactivity in CAS and cerebrovascular disease patients are still limited and need further validation in large multicenter studies. This review covers an important topic in the field of antiplatelet therapy for cerebral endovascular procedures and CAS.
authors.affiliation: Department 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.
authors.forename: Jorge
authors.initials: J
authors.lastname: Duconge
authors.affiliation: Department of Medicine, School of Medicine, University of Puerto Rico Medical Sciences Campus (UPR-MSC), San Juan, PR, United States.
authors.forename: Dagmar F
authors.initials: DF
authors.lastname: Hernandez-Suarez
mesh_terms: D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000628:therapy*; D002561:Cerebrovascular Disorders / Q000000981:diagnostic imaging / Q000628:therapy*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D057510:Endovascular Procedures / Q000009:adverse effects / Q000295:instrumentation*; D006801:Humans; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012307:Risk Factors; D015607:Stents; D013927:Thrombosis / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics / Q000517:prevention & control*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: CYP2C19; Clopidogrel; carotid artery
  stenting; cerebral endovascular procedures; ischemic stroke; pharmacogenetics