Title:Potential Usefulness of Clopidogrel Pharmacogenetics in Ce rebral Endovascular Procedures and Carotid Artery Stenting
Volume: 12
Issue: 1
Author(s): Jorge Duconge*Dagmar F. Hernandez-Suarez
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
Keywords:
Clopidogrel, pharmacogenetics, CYP2C19, ischemic stroke, cerebral endovascular procedures, carotid artery
stenting.
Abstract: Background: 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.
Objective: 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.
Method: 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.
Results: 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.
Conclusion: 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.