Influence of Genetic Polymorphisms on Clopidogrel Response and Clinical Outcomes in Patients with Acute Ischemic Stroke CYP2C19 Genotype on Clopidogrel Response

• Published in: CNS neuroscience & therapeutics Vol. 21; no. 9; pp. 692 - 697
• Main Authors: Han, Yan, Lv, Hui‐Hui, Liu, Xu, Dong, Qiang, Yang, Xiao‐Li, Li, Shi‐Xu, Wu, Shuai, Jiang, Jian‐Ming, Luo, Zheng, Zhu, De‐Sheng, Zhang, Yi, Zheng, Yi, Guan, Yang‐Tai, Xu, Jian‐Feng
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.09.2015; John Wiley and Sons Inc
• Subjects: Aged; Biomarkers, Pharmacological; Brain Ischemia - drug therapy; Brain Ischemia - genetics; Cardiology; Clinical outcomes; Clopidogrel; CYP2C19; Cytochrome P-450 CYP2C19 - genetics; Female; Follow-Up Studies; Genotype; Genotype & phenotype; Humans; Ischemic stroke; Male; Original; Platelet Aggregation Inhibitors - therapeutic use; Platelet Function Tests; Polymorphism, Single Nucleotide; Prospective Studies; Random Allocation; Stroke; Stroke - drug therapy; Stroke - genetics; The VerifyNow P2Y12 test; Ticlopidine - analogs & derivatives; Ticlopidine - therapeutic use; Treatment Outcome; Clopidogrel; Ischemic stroke; CYP2C19; The VerifyNow P2Y12 test
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.12426

Summary Objectives This study sought to evaluate the influence of the genetic polymorphisms on platelet reactivity and clinical outcomes in acute ischemic stroke patients taking clopidogrel. Background Little research has been published on relationships between genetic polymorphisms, platelet reactivity, and clinical outcomes in stroke patients treated with clopidogrel. Methods Patients hospitalized in Changhai Hospital with acute ischemic stroke were randomly enrolled into treatment with a 75‐mg daily maintenance dose of clopidogrel. Genotyping was detected by the MassARRAY iPLEX genotyping system (Sequenom Inc, San Diego, CA), and platelet reactivity was evaluated by the VerifyNow P2Y12 test (Accumetrics Inc., San Diego, CA). Sixteen single nucleotide polymorphisms (SNPs) within 9 genes were selected and high on‐clopidogrel platelet reactivity (HPR) was defined as P2Y12 reaction units (PRU) value ≥230. The primary endpoint was ischemic events, including major adverse cardiac events (MACE), recurrence of stroke, transient ischemic attack (TIA), and the composite of vascular death, and the secondary endpoint was bleeding. Results Of the 345 patients recruited, 275 (79.7%) patients were followed up for 1 year and 122 (35.4%) patients were categorized as HPR. Among the SNPs selected, only the CYP2C19*2 allele and the CYP2C19*3 allele were statistically significantly associated with PRU (P < 0.001 and P = 0.003, respectively). Similarly, the prevalence of HPR was associated with CYP2C19*2 and CYP2C19*3 (P < 0.001 and P = 0.001, respectively). During the 1 year of follow‐up, a total of 64 (23.3%) cases of clinical events occurred, including 60 ischemic events and 4 bleeding events. There were no correlation between CYP2C19 variant alleles and clinical outcomes (P > 0.05), but a statistically significant relevance was found between the HPR and the ischemic events in 1 year of follow‐up (P = 0.001). Conclusions CYP2C19*2 and CYP2C19*3 had a significant impact on clopidogrel response, but was not associated with ischemic events during 1 year of follow‐up in patients with acute ischemic stroke. HPR was an independent risk factor for ischemic events, and the VerifyNow P2Y12 test may be available to guide individualized antiplatelet therapies in stroke patients in China.