Dataset Information

CYP2C19 and ABCB1 genetic polymorphisms correlate with the recurrence of ischemic cardiovascular adverse events after clopidogrel treatment.

ABSTRACT:

Background

This study was aimed to investigate the correlation between CYP2C19 and ABCB1 polymorphisms and the recurrence of ischemic cardiovascular adverse events in patients with coronary artery disease treated with clopidogrel.

Methods

A total of 168 patients with coronary heart disease who underwent PCI operation and received clopidogrel treatment were enrolled. Dual antiplatelet therapy was applied to the treatment of patients for 2 years. Thromboelastography was used to test the efficiency of blood coagulation. Polymerase chain reaction (PCR) was used to detect CYP2C19 and ABCB1 3435CT polymorphisms. One-year follow-up visit was carried out to record the incidence of cardiovascular adverse events after drug-eluting stent implantation was inset.

Results

Follow-up visit results suggested that the patients with high on-treatment platelet reactivity (HPR) had a higher recurrence rate of cardiovascular adverse events after PCI operation and clopidogrel treatment. Gene polymorphism testing results indicated that patients with CYP2C19*3 had a significantly higher incidence of HPR, whereas CYP2C19*2 and ABCB1 3435CT were not significantly correlated with HPR. Multivariable logistic regression analysis showed that CYP2C19*3 might be an independent predictive factor of post-PCI HPR. In addition, CYP2C19*3 as well as post-PCI HPR could function as independent predictive factors of cardiovascular adverse events.

Conclusion

CYP2C19*3 polymorphism could be an important predictive factor of HPR and ischemic cardiovascular adverse events after clopidogrel treatment.

SUBMITTER: Hou X

PROVIDER: S-EPMC6816974 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesThis study sought to evaluate the influence of the genetic polymorphisms on platelet reactivity and clinical outcomes in acute ischemic stroke patients taking clopidogrel.BackgroundLittle research has been published on relationships between genetic polymorphisms, platelet reactivity, and clinical outcomes in stroke patients treated with clopidogrel.MethodsPatients 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.ResultsOf 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).ConclusionsCYP2C19*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.

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