title: Switching from prasugrel to clopidogrel based on Cytochrome P450 2C19 genotyping in East Asian patients stabilized after acute myocardial infarction.
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.
authors.affiliation: a Division of Cardiology, Department of Internal Medicine , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: a Division of Cardiology, Department of Internal Medicine , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.|b Division of Cardiology, Department of Medicine , Emory University School of Medicine , Atlanta , GA , USA.
authors.forename: Sung Gyun
authors.initials: SG
authors.lastname: Ahn
authors.affiliation: a Division of Cardiology, Department of Internal Medicine , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Jun-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: a Division of Cardiology, Department of Internal Medicine , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Youn
authors.affiliation: a Division of Cardiology, Department of Internal Medicine , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Ahn
authors.affiliation: a Division of Cardiology, Department of Internal Medicine , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Jang-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: a Division of Cardiology, Department of Internal Medicine , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Byung-Su
authors.initials: BS
authors.lastname: Yoo
authors.affiliation: a Division of Cardiology, Department of Internal Medicine , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: a Division of Cardiology, Department of Internal Medicine , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Junghan
authors.initials: J
authors.lastname: Yoon
authors.affiliation: c Department of Laboratory Medicine , Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Juwon
authors.initials: J
authors.lastname: Kim
authors.affiliation: d Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine , Wonju , Republic of Korea.
authors.forename: Eunhee
authors.initials: E
authors.lastname: Choi
authors.affiliation: b Division of Cardiology, Department of Medicine , Emory University School of Medicine , Atlanta , GA , USA.|e Division of Cardiology, Department of Internal Medicine , University of Ulsan College of Medicine, Gangneung Asan Hospital , Gangneung , Republic of Korea.
authors.forename: Sang-Yong
authors.initials: SY
authors.lastname: Yoo
authors.affiliation: b Division of Cardiology, Department of Medicine , Emory University School of Medicine , Atlanta , GA , USA.
authors.forename: Olivia Y
authors.initials: OY
authors.lastname: Hung
authors.affiliation: b Division of Cardiology, Department of Medicine , Emory University School of Medicine , Atlanta , GA , USA.
authors.forename: Habib
authors.initials: H
authors.lastname: Samady
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D057915:Drug Substitution; D005260:Female; D005838:Genotype; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D062645:Percutaneous Coronary Intervention; D000071184:Pharmacogenomic Variants; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D010979:Platelet Function Tests; D020641:Polymorphism, Single Nucleotide; D000068799:Prasugrel Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: Clopidogrel; myocardial infarction; pharmacogenetics; prasugrel