Association betweenCYP2C19Polymorphisms and Outcomes in Cerebral Endovascular Therapy

Abstract

BACKGROUND AND PURPOSE: Differing responses to clopidogrel following endovascular treatment of cerebrovascular diseases may increase the risk of vascular complications. CYP2C19 gene polymorphisms influence clopidogrel activity. We aimed to study the clinical impact of CYP2C19 gene polymorphisms in patients undergoing endovascular treatment.

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

“…A prospective, longitudinal, observational study by Lin et al (2016) in 108 clopidogrel-treated patients undergoing endovascular treatment was conducted to test association among CYP2C19 genotypes and clopidogrel responsiveness and clinical outcomes [33]. Participants received DAPT with clopidogrel (75 mg daily) and aspirin (150 mg/day) since at least 3 days before interventions and were then followed up over 3 months.…”

“…Participants received DAPT with clopidogrel (75 mg daily) and aspirin (150 mg/day) since at least 3 days before interventions and were then followed up over 3 months. Based on their findings, authors concluded that individuals who underwent elective neurointervention for intracranial aneurysms or stenosis have increased risk of ischemic events following endovascular treatment, independent of clopidogrel responsiveness, if they are carriers of the CYP2C19 *17 variant [33]. Indeed, they found a significantly higher proportion of CYP2C19 *17 carriers who experienced ischemic events (32.1%) as compared with wild-types (11.4%; p=0.04; OR=3.7), which remained significant after adjustment for age (p=0.03; OR=4.0) and ex vivo clopidogrel response (p=0.04; OR=4.5).…”

“…Indeed, they found a significantly higher proportion of CYP2C19 *17 carriers who experienced ischemic events (32.1%) as compared with wild-types (11.4%; p=0.04; OR=3.7), which remained significant after adjustment for age (p=0.03; OR=4.0) and ex vivo clopidogrel response (p=0.04; OR=4.5). No significant differences between wild-types and the other known CYP2C19 genetic variants associated with clopidogrel resistance and adverse cardiovascular outcomes (i.e., *2 and *3) were identified [33]. …”

Influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling

“…Different responses to clopidogrel may be related to CYP2C19 genetic polymorphisms 13. Several studies have shown that carriers with CYP2C19 alleles *2 or *3 had significantly lower levels of the active metabolite of clopidogrel, and could be considered as risk predictors for clinical outcomes in ACS or patients with cerebrovascular ischemic stroke.…”

“…Owing to the different physiopathologic mechanism and the potential risk of rupture, inadequate antiplatelet therapy for patients with intracranial aneurysm might cause fatal complications. A loading dose of 300 mg clopidogrel or its long-term use, which was the standard dosage for a cardiovascular stent-placement procedure, might increase the risk of bleeding or rebleeding in intracranial aneurysms 13 20. On the other hand, insufficient platelet inhibition has a significant association with the incidence of thromboembolic complications 15.…”