Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2015 Sep;21(9):692-7.
doi: 10.1111/cns.12426. Epub 2015 Jul 15.

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

Yan Han  1 , Hui-Hui Lv  1 , Xu Liu  2   3 , Qiang Dong  4 , Xiao-Li Yang  1 , Shi-Xu Li  1 , Shuai Wu  1 , Jian-Ming Jiang  1 , Zheng Luo  1 , De-Sheng Zhu  1 , Yi Zhang  1 , Yi Zheng  1 , Yang-Tai Guan  1   5 , Jian-Feng Xu  2   3   6   7
Affiliations
Observational Study

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

Yan Han et al. CNS Neurosci Ther. 2015 Sep.

Abstract

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.

Keywords: CYP2C19; Clopidogrel; Ischemic stroke; The VerifyNow P2Y12 test.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRU value in different genotypes for CYP2C19*2 (c.681G>A; rs4244285) GG, CYP2C19 *1*1; AG: CYP2C19 *1*2; AA: CYP2C19 *2*2.
Figure 2
Figure 2
PRU value in different genotypes for CYP2C19*3 (c.636G>A; rs4986893) GG, CYP2C19 *1*1; AG: CYP2C19 *1*3.
Figure 3
Figure 3
Kaplan–Meier cumulative event rates of the primary endpoint (MACE, recurrence of stroke, TIA, and the composite of vascular death) based on the presence of HPR during the follow‐up period (P = 0.003).
See this image and copyright information in PMC

References

    1. Yang G, Wang Y, Zeng Y, et al. Rapid health transition in China, 1990‐2010: findings from the Global Burden of Disease Study 2010. Lancet 2013;381:1987–2015. - PMC - PubMed
    1. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA Guideline Update for the Management of Patients With Unstable Angina and Non–ST‐Segment Elevation Myocardial Infarction—2002: Summary Article A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). Circulation 2002;106:1893–1900. - PubMed
    1. Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: A guideline for healthcare professionals from the american heart association/american stroke association. Stroke 2011;42:227–276. - PubMed
    1. Parodi G, Marcucci R, Valenti R, et al. High residual platelet reactivity after clopidogrel loading and long‐term cardiovascular events among patients with acute coronary syndromes undergoing PCI. JAMA 2011;306:1215–1223. - PubMed
    1. Price MJ, Angiolillo DJ, Teirstein PS, et al. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: A time‐dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Circulation 2011;124:1132–1137. - PubMed

Publication types

MeSH terms