• J Formos Med Assoc · Sep 2022

    Multicenter Study

    Effect of CYP2C19 status on platelet reactivity in Taiwanese acute coronary syndrome patients switching to prasugrel from clopidogrel: Switch Study.

    • Feng-Yu Kuo, Cheng-Han Lee, Wei-Ren Lan, Cheng-Huang Su, Wen-Lieng Lee, Yi-Chih Wang, Wei-Shiang Lin, Pao-Hsien Chu, Tse-Min Lu, Ping-Han Lo, Shuji Tsukiyama, Wei-Chen Yang, Li-Chung Cheng, Chien-Lung Huang, Wei-Hsian Yin, and Ping-Yen Liu.
    • Division of Cardiology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, 813414, Taiwan.
    • J Formos Med Assoc. 2022 Sep 1; 121 (9): 1786-1797.

    Background/PurposePharmacogenetics is a potential driver of the "East Asian paradox," in which East Asian acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy (DAPT) with clopidogrel following percutaneous coronary intervention (PCI) demonstrate higher levels of platelet reactivity on treatment than Western patients, yet have lower ischemic risk and higher bleeding risk at comparable doses. However, the impact of pharmacogenetics, particularly regarding CYP2C19 genotype, on the pharmacodynamics of P2Y12 inhibitors has not been extensively studied in Taiwanese ACS patients as yet.MethodsCYP2C19 genotyping and pharmacogenetic analysis was conducted on 102 subjects from the Switch Study, a multicenter, single-arm, open-label intervention study that examined the effects on platelet activity and clinical outcomes of switching from clopidogrel (75 mg daily) to low-dose prasugrel (3.75 mg daily) for maintenance DAPT after PCI in 203 Taiwanese ACS patients.ResultsGenotyping results revealed that 43.1% were CYP2C19 extensive metabolizers (EM), while 56.9% were reduced metabolizers (RM). After switching to prasugrel, mean P2Y12 reaction units (PRU) values were significantly reduced in both EM and RM populations, while the proportion of high on-treatment platelet reactivity (HPR) patients significantly declined in RM patients. No increase in bleeding risk after switching was observed during follow-up. Multivariate analysis indicated that for RM patients, low estimated glomerular filtration rate (eGFR) and low hemoglobin were associated with greater HPR risk on clopidogrel, but not after switching to prasugrel.ConclusionSwitching to low-dose prasugrel from clopidogrel reduced mean PRU levels and proportion of HPR patients, with more significant reduction in RM patients.Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.

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