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Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome.

ABSTRACT: OBJECTIVE:To evaluate the contribution of six polymorphisms to the platelet reactivity in patients with acute coronary syndrome (ACS) treated with clopidogrel. METHODS:Cross-sectional study of 278 consecutive patients with ACS. Detailed clinical information for each patient was collected and genotypes (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*17, CYP3A4*1B, and PON1-Q192R) were evaluated with TaqMan® and KASPar® assays. Platelet reactivity was measured with VerifyNow®. RESULTS:Mean age of patients was 66±11 years and 182 (65.5%) patients presented ACS without ST-segment elevation. A total of 206 (74.1%) patients presented poor response to clopidogrel (PRC). CYP2C19*2 polymorphism (p=0.038) was associated with PRC in the univariate setting. In the multiple logistic regression analysis, the risk factors for PRC were the presence of CYP3A4*1B allele (odds ratio [OR] 4.03; 95% confidence interval [CI] 1.01-16.34), age (OR 1.43; 95% CI 1.03-2.00), and body mass index (OR 4.05; 95% CI 1.21-13.43), whereas elevated hemoglobin was a protective factor. Discrimination of PRC through the model that included the six polymorphisms added modest information to the model based on clinical variables (C statistic difference 3.9%). CONCLUSION:CYP3A4*1B allele may be an independent determinant of PRC in patients with ACS, although the variability in response to clopidogrel explained by the six polymorphisms is poor when compared to clinical variables.

SUBMITTER: Garcia-Lagunar MH

PROVIDER: S-EPMC5469111 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome.

García-Lagunar María Henar MH Consuegra-Sánchez Luciano L Conesa-Zamora Pablo P Ruiz-Cosano Javier J Soria-Arcos Federico F García de Guadiana Luis L Vivar Pedro Cano PC Castillo-Moreno Juan Antonio JA Melgarejo-Moreno Antonio A

Anatolian journal of cardiology 20170201 4

<h4>Objective</h4>To evaluate the contribution of six polymorphisms to the platelet reactivity in patients with acute coronary syndrome (ACS) treated with clopidogrel.<h4>Methods</h4>Cross-sectional study of 278 consecutive patients with ACS. Detailed clinical information for each patient was collected and genotypes (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*17, CYP3A4*1B, and PON1-Q192R) were evaluated with TaqMan® and KASPar® assays. Platelet reactivity was measured with VerifyNow®.<h4>Results</h ...[more]

PMID: 28179614

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Project description:Background: The combination of clopidogrel and aspirin is recommended for the treatment of patients with acute minor stroke or transient ischemic attack (TIA). However, with varied clopidogrel resistance (often due to CYP2C19 loss-of-function (LOF) alleles), alternatives like ticagrelor have been suggested. Previous studies showed that ticagrelor had a lower platelet reactivity assessed by VerifyNow P2Y12 assay than clopidogrel. We aimed to compare the effect of ticagrelor vs. clopidogrel on platelet reactivity assessed by a different method (Aggrestar platelet function analyzer) and analyze whether CYP2C19 genotypes were involved. Methods: A pre-specified subgroup analysis of a randomized controlled trial- Platelet Reactivity in Acute Non-disabling Cerebrovascular Events (PRINCE) was conducted. Patients with minor stroke or TIA were randomized for treatment with ticagrelor plus aspirin or clopidogrel plus aspirin. Platelet reactivity was assessed by Aggrestar (PL) platelet function analyzer and high on-treatment platelet reactivity (HOPR) on ticagrelor or clopidogrel was compared. Clinical outcomes included any stroke, composite vascular events and bleeding events within 90 days. Patients were categorized into carriers and non-carriers according to the carrier status of CYP2C19 LOF alleles. Results: Among 675 patients enrolled in the PRINCE trial, 387 patients were included in this subgroup: 197 were randomized to ticagrelor plus aspirin and 190 to clopidogrel plus aspirin. At 90 ± 7 days, compared with clopidogrel/aspirin group, the proportion of HOPR in ticagrelor/aspirin group was significantly lower (19.6 vs. 40.8%, P < 0.001). No significant treatment-by-genotype interactions were found (P for interaction = 0.12). Within 90 days, a trend toward a lower risk of new stroke in ticagrelor/aspirin compared to clopidogrel/aspirin was observed (4.6 vs. 9.5%, HR 0.47, 95% CI 0.21-1.05, P = 0.06). Conclusions: Ticagrelor is superior to clopidogrel in inhibiting platelet reactivity measured by the PL platelet function analyzer among patients with acute minor stroke or TIA. Our study confirmed the finding of the main analysis of PRINCE trial in a different assay. Large randomized controlled trials are needed to evaluate our findings. Clinical Trial Registration: Clinicaltrials.gov NCT02506140.

Dataset Information

Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome.

Publications

Genotyping of six clopidogrel-metabolizing enzyme polymorphisms has a minor role in the assessment of platelet reactivity in patients with acute coronary syndrome.

Similar Datasets

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