Switching from prasugrel to clopidogrel based on Cytochrome P450 2C19 genotyping in East Asian patients stabilized after acute myocardial infarction

Ji Hyun Lee, Sung Gyun Ahn, Junwon Lee, Youngjin Youn, Minsoo Ahn, Jang Young Kim, Byungsu Yoo, Seunghwan Lee, Junghan Yoon, Juwon Kim, Eunhee Choi, Sang Yong Yoo, Olivia Y. Hung, Habib Samady

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

To evaluate the pharmacodynamic efficacy of de-escalating P2Y12 inhibition from prasugrel to clopidogrel based on cytochrome P450 (CYP) 2C19 genotyping, we genotyped 50 Korean patients with AMI who underwent percutaneous coronary intervention (PCI) for CYP2C19 *2,*3, or *17 using real-time PCR. They were discharged on prasugrel 10 mg daily. A control group of 48 AMI patients who underwent PCI and were discharged on clopidogrel but did not undergo genotyping was identified retrospectively. Based on genotyping results available at 3 weeks, 12 patients found to have 2 copies of either CYP2C19 *2 or *3 loss of function alleles continued prasugrel while the remaining 38 patients switched to clopidogrel 75 mg daily. The rate of patients within the therapeutic window (TW) of on-treatment platelet reactivity (OPR), 85<P2Y12 reactivity unit (PRU) ≤275, was compared in the genotype-directed cohort before (3 weeks) and after genotype-directed antiplatelet treatment (5 weeks), as well as with the control cohort at 5 weeks. In the genotype-directed group, there was an increase in the proportion of patients within the TW after genotype-directed antiplatelet treatment (48–76%, p=0.007), primarily driven by a decrease of patients with PRU <85 (52–16%, p <0.001). The proportion of patients within the TW was similar between the genotype-guided and control groups (76% vs. 72.9% p=0.726). In conclusion, individualized antiplatelet regimens based on CYP2C19 genotyping may improve likelihood of achieving a TW of OPR compared to fixed dose of prasugrel 10 mg during maintenance periods of AMI in East Asians.

Original languageEnglish
Pages (from-to)301-307
Number of pages7
JournalPlatelets
Volume27
Issue number4
DOIs
Publication statusPublished - 2016 May 18

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clopidogrel
Cytochrome P-450 Enzyme System
Myocardial Infarction
Genotype
Percutaneous Coronary Intervention
Therapeutics
Blood Platelets
Control Groups
Prasugrel Hydrochloride

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Lee, Ji Hyun ; Ahn, Sung Gyun ; Lee, Junwon ; Youn, Youngjin ; Ahn, Minsoo ; Kim, Jang Young ; Yoo, Byungsu ; Lee, Seunghwan ; Yoon, Junghan ; Kim, Juwon ; Choi, Eunhee ; Yoo, Sang Yong ; Hung, Olivia Y. ; Samady, Habib. / Switching from prasugrel to clopidogrel based on Cytochrome P450 2C19 genotyping in East Asian patients stabilized after acute myocardial infarction. In: Platelets. 2016 ; Vol. 27, No. 4. pp. 301-307.
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abstract = "To evaluate the pharmacodynamic efficacy of de-escalating P2Y12 inhibition from prasugrel to clopidogrel based on cytochrome P450 (CYP) 2C19 genotyping, we genotyped 50 Korean patients with AMI who underwent percutaneous coronary intervention (PCI) for CYP2C19 *2,*3, or *17 using real-time PCR. They were discharged on prasugrel 10 mg daily. A control group of 48 AMI patients who underwent PCI and were discharged on clopidogrel but did not undergo genotyping was identified retrospectively. Based on genotyping results available at 3 weeks, 12 patients found to have 2 copies of either CYP2C19 *2 or *3 loss of function alleles continued prasugrel while the remaining 38 patients switched to clopidogrel 75 mg daily. The rate of patients within the therapeutic window (TW) of on-treatment platelet reactivity (OPR), 85<P2Y12 reactivity unit (PRU) ≤275, was compared in the genotype-directed cohort before (3 weeks) and after genotype-directed antiplatelet treatment (5 weeks), as well as with the control cohort at 5 weeks. In the genotype-directed group, there was an increase in the proportion of patients within the TW after genotype-directed antiplatelet treatment (48–76{\%}, p=0.007), primarily driven by a decrease of patients with PRU <85 (52–16{\%}, p <0.001). The proportion of patients within the TW was similar between the genotype-guided and control groups (76{\%} vs. 72.9{\%} p=0.726). In conclusion, individualized antiplatelet regimens based on CYP2C19 genotyping may improve likelihood of achieving a TW of OPR compared to fixed dose of prasugrel 10 mg during maintenance periods of AMI in East Asians.",
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Switching from prasugrel to clopidogrel based on Cytochrome P450 2C19 genotyping in East Asian patients stabilized after acute myocardial infarction. / Lee, Ji Hyun; Ahn, Sung Gyun; Lee, Junwon; Youn, Youngjin; Ahn, Minsoo; Kim, Jang Young; Yoo, Byungsu; Lee, Seunghwan; Yoon, Junghan; Kim, Juwon; Choi, Eunhee; Yoo, Sang Yong; Hung, Olivia Y.; Samady, Habib.

In: Platelets, Vol. 27, No. 4, 18.05.2016, p. 301-307.

Research output: Contribution to journalArticle

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T1 - Switching from prasugrel to clopidogrel based on Cytochrome P450 2C19 genotyping in East Asian patients stabilized after acute myocardial infarction

AU - Lee, Ji Hyun

AU - Ahn, Sung Gyun

AU - Lee, Junwon

AU - Youn, Youngjin

AU - Ahn, Minsoo

AU - Kim, Jang Young

AU - Yoo, Byungsu

AU - Lee, Seunghwan

AU - Yoon, Junghan

AU - Kim, Juwon

AU - Choi, Eunhee

AU - Yoo, Sang Yong

AU - Hung, Olivia Y.

AU - Samady, Habib

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N2 - To evaluate the pharmacodynamic efficacy of de-escalating P2Y12 inhibition from prasugrel to clopidogrel based on cytochrome P450 (CYP) 2C19 genotyping, we genotyped 50 Korean patients with AMI who underwent percutaneous coronary intervention (PCI) for CYP2C19 *2,*3, or *17 using real-time PCR. They were discharged on prasugrel 10 mg daily. A control group of 48 AMI patients who underwent PCI and were discharged on clopidogrel but did not undergo genotyping was identified retrospectively. Based on genotyping results available at 3 weeks, 12 patients found to have 2 copies of either CYP2C19 *2 or *3 loss of function alleles continued prasugrel while the remaining 38 patients switched to clopidogrel 75 mg daily. The rate of patients within the therapeutic window (TW) of on-treatment platelet reactivity (OPR), 85<P2Y12 reactivity unit (PRU) ≤275, was compared in the genotype-directed cohort before (3 weeks) and after genotype-directed antiplatelet treatment (5 weeks), as well as with the control cohort at 5 weeks. In the genotype-directed group, there was an increase in the proportion of patients within the TW after genotype-directed antiplatelet treatment (48–76%, p=0.007), primarily driven by a decrease of patients with PRU <85 (52–16%, p <0.001). The proportion of patients within the TW was similar between the genotype-guided and control groups (76% vs. 72.9% p=0.726). In conclusion, individualized antiplatelet regimens based on CYP2C19 genotyping may improve likelihood of achieving a TW of OPR compared to fixed dose of prasugrel 10 mg during maintenance periods of AMI in East Asians.

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