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Serum interleukin-18 levels as a predictor for patients with genetic dysfunction of cytochrome P450 2C19 in dual antiplatelet therapy with clopidogrel.
J Cardiol. 2020 Jun 29 [Online ahead of print]JC

Abstract

BACKGROUND

P2Y12 reaction unit (PRU) is an index of platelet activity upon treatment with clopidogrel. In spite of suitable P2Y12 reactions in dual antiplatelet therapy (DAPT) with clopidogrel after percutaneous coronary intervention (PCI), cardiovascular events actually occur in some patients, possibly due to a genetic dysfunction of cytochrome P450 2C19 (CYP2C19), which is a major metabolic enzyme of clopidogrel. As testing the CYP2C19 phenotypes to predict such patients may lack general versatility in daily clinical practice, the aim of this study was to examine whether measuring the blood levels of some cytokines in patients showing desirable PRUs in DAPT with clopidogrel could be a substitute for testing the CYP2C19 phenotypes.

METHODS

We analyzed relationships among PRU, serum levels of 51 cytokines, and CYP2C19 phenotypes in 22 patients receiving DAPT with aspirin and clopidogrel after PCI.

RESULTS

Seventeen, 18, and 19 of 22 patients indicated PRU ≤ 208, PRU ≤ 230, and PRU ≤ 262, respectively. Approximately 60% of the patients had a genetically metabolic dysfunction of CYP2C19, and the serum levels of interleukin-18 were independently increased in those patients (p = 0.024 in patients with PRU ≤ 208, p = 0.021 with PRU ≤ 230, and p = 0.020 with PRU ≤ 262). The area under the curves in plot receiver operating characteristics curves for the serum levels of interleukin-18 were 0.94, 0.96, and 0.90 in the non-extensive metabolizer patients with PRU ≤ 208, PRU ≤ 230, and PRU ≤ 262, respectively.

CONCLUSIONS

The serum levels of interleukin-18 may be a predictor to diagnose patients who receive undesirable DAPT with clopidogrel, possibly due to the genetic dysfunction of CYP2C19 in spite of suitable P2Y12 reactions after PCI.

Authors+Show Affiliations

Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. Electronic address: sasaken@med.kurume-u.ac.jp.Biostatistics Center, Kurume University, Kurume, Japan.Daiichi Sankyo Co., Ltd., Tokyo, Japan.Daiichi Sankyo Co., Ltd., Tokyo, Japan.Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32616329

Citation

Ishimatsu, Takashi, et al. "Serum Interleukin-18 Levels as a Predictor for Patients With Genetic Dysfunction of Cytochrome P450 2C19 in Dual Antiplatelet Therapy With Clopidogrel." Journal of Cardiology, 2020.
Ishimatsu T, Sasaki KI, Kakuma T, et al. Serum interleukin-18 levels as a predictor for patients with genetic dysfunction of cytochrome P450 2C19 in dual antiplatelet therapy with clopidogrel. J Cardiol. 2020.
Ishimatsu, T., Sasaki, K. I., Kakuma, T., Harada, A., Hirakawa, Y., Fukumoto, Y., & Ueno, T. (2020). Serum interleukin-18 levels as a predictor for patients with genetic dysfunction of cytochrome P450 2C19 in dual antiplatelet therapy with clopidogrel. Journal of Cardiology. https://doi.org/10.1016/j.jjcc.2020.06.008
Ishimatsu T, et al. Serum Interleukin-18 Levels as a Predictor for Patients With Genetic Dysfunction of Cytochrome P450 2C19 in Dual Antiplatelet Therapy With Clopidogrel. J Cardiol. 2020 Jun 29; PubMed PMID: 32616329.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serum interleukin-18 levels as a predictor for patients with genetic dysfunction of cytochrome P450 2C19 in dual antiplatelet therapy with clopidogrel. AU - Ishimatsu,Takashi, AU - Sasaki,Ken-Ichiro, AU - Kakuma,Tatsuyuki, AU - Harada,Atsushi, AU - Hirakawa,Yuji, AU - Fukumoto,Yoshihiro, AU - Ueno,Takafumi, Y1 - 2020/06/29/ PY - 2020/01/28/received PY - 2020/05/18/revised PY - 2020/05/21/accepted PY - 2020/7/4/pubmed PY - 2020/7/4/medline PY - 2020/7/4/entrez KW - Cytokine KW - Diagnostic biomarker KW - P2Y(12) reaction unit KW - Percutaneous coronary intervention JF - Journal of cardiology JO - J Cardiol N2 - BACKGROUND: P2Y12 reaction unit (PRU) is an index of platelet activity upon treatment with clopidogrel. In spite of suitable P2Y12 reactions in dual antiplatelet therapy (DAPT) with clopidogrel after percutaneous coronary intervention (PCI), cardiovascular events actually occur in some patients, possibly due to a genetic dysfunction of cytochrome P450 2C19 (CYP2C19), which is a major metabolic enzyme of clopidogrel. As testing the CYP2C19 phenotypes to predict such patients may lack general versatility in daily clinical practice, the aim of this study was to examine whether measuring the blood levels of some cytokines in patients showing desirable PRUs in DAPT with clopidogrel could be a substitute for testing the CYP2C19 phenotypes. METHODS: We analyzed relationships among PRU, serum levels of 51 cytokines, and CYP2C19 phenotypes in 22 patients receiving DAPT with aspirin and clopidogrel after PCI. RESULTS: Seventeen, 18, and 19 of 22 patients indicated PRU ≤ 208, PRU ≤ 230, and PRU ≤ 262, respectively. Approximately 60% of the patients had a genetically metabolic dysfunction of CYP2C19, and the serum levels of interleukin-18 were independently increased in those patients (p = 0.024 in patients with PRU ≤ 208, p = 0.021 with PRU ≤ 230, and p = 0.020 with PRU ≤ 262). The area under the curves in plot receiver operating characteristics curves for the serum levels of interleukin-18 were 0.94, 0.96, and 0.90 in the non-extensive metabolizer patients with PRU ≤ 208, PRU ≤ 230, and PRU ≤ 262, respectively. CONCLUSIONS: The serum levels of interleukin-18 may be a predictor to diagnose patients who receive undesirable DAPT with clopidogrel, possibly due to the genetic dysfunction of CYP2C19 in spite of suitable P2Y12 reactions after PCI. SN - 1876-4738 UR - https://www.unboundmedicine.com/medline/citation/32616329/Serum_interleukin-18_levels_as_a_predictor_for_patients_with_genetic_dysfunction_of_cytochrome_P450_2C19_in_dual_antiplatelet_therapy_with_clopidogrel L2 - https://linkinghub.elsevier.com/retrieve/pii/S0914-5087(20)30193-3 DB - PRIME DP - Unbound Medicine ER -
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