Factors associated with clopidogrel resistance and clinical outcomes in ischemic cerebrovascular disease: A retrospective study

J Stroke Cerebrovasc Dis. 2024 Jun;33(6):107684. doi: 10.1016/j.jstrokecerebrovasdis.2024.107684. Epub 2024 Mar 20.

Abstract

Objective: Clopidogrel resistance may lead to the recurrence of cerebrovascular diseases. We aimed to identify potential factors associated with clopidogrel resistance and evaluate the clinical outcomes of the patients.

Materials and methods: In this retrospective study, patients with ischemic cerebrovascular disease treated with clopidogrel were included and classified into 2 groups according to the adenosine diphosphate (ADP)-induced platelet aggregation. Patients with the ADP inhibition rate of <30 % were included in clopidogrel resistance group, otherwise were included in clopidogrel sensitive group. CYP2C19 genotype and other clinical data were analyzed to identify factors and clinical features in the multivariate analysis. The outcomes were vascular events in 6 months.

Results: In total, 139 patients were enrolled with 81 (58.27 %) in clopidogrel sensitive group and 58 (41.73 %) in clopidogrel resistance group. Female and CYP2C19 *2*3 carrying were risk factors for clopidogrel resistance, and female was an independent risk factor (OR 2.481, 95 % CI 1.066-5.771, P=0.035). The clopidogrel resistance group showed a higher use rate of argatroban (P=0.030) and a lower arachidonic acid-induced inhibition of platelet aggregation (P=0.036). Clopidogrel resistance was related to the progressing stroke (HR 3.521, 95 % CI 1.352-9.170, P=0.010), but had no influence on the bleeding events (P>0.05).

Conclusions: The risk of clopidogrel resistance increased significantly in female patients. Patients with clopidogrel resistance may have an increased incidence of stroke progression in the acute phase.

Keywords: CYP2C19; Clopidogrel resistance; Ischemic cerebrovascular disease; Risk factor; Stroke.

MeSH terms

  • Aged
  • Brain Ischemia / diagnosis
  • Brain Ischemia / drug therapy
  • Clopidogrel* / adverse effects
  • Clopidogrel* / therapeutic use
  • Cytochrome P-450 CYP2C19* / genetics
  • Cytochrome P-450 CYP2C19* / metabolism
  • Drug Resistance*
  • Female
  • Humans
  • Ischemic Stroke / diagnosis
  • Ischemic Stroke / drug therapy
  • Male
  • Middle Aged
  • Pharmacogenomic Variants
  • Platelet Aggregation Inhibitors* / adverse effects
  • Platelet Aggregation Inhibitors* / therapeutic use
  • Platelet Aggregation* / drug effects
  • Platelet Function Tests
  • Recurrence
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Clopidogrel
  • Platelet Aggregation Inhibitors
  • Cytochrome P-450 CYP2C19
  • CYP2C19 protein, human