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Comparison of platelet aggregation response in switching regimen from prasugrel to clopidogrel between CYP2C19 extensive versus non-extensive metabolizers

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Abstract

Little is known about the response of platelet aggregation in patients with acute coronary syndrome (ACS) when prasugrel is changed to clopidogrel. In this study, we evaluated the pharmacodynamic effects of this medication switch. Twenty-one consecutive ACS patients received prasugrel 20 mg as a loading dose before emergent percutaneous coronary intervention and 3.75 mg as a maintenance dose on days 2–7 (prasugrel phase). From day 8, prasugrel was switched to clopidogrel 75 mg/day (clopidogrel phase). P2Y12 reaction units (PRU) were measured 2–4 h after prasugrel loading, and on days 7, 11, 13, 15, and 42. Eight patients had the CYP2C19 extensive metabolizer (EM) genotype variant, while 13 were non-EM. In the EM group, no changes were observed in PRU level between days 7 and 15 (136.8 ± 51.2 vs. 166.2 ± 41.9, P = 0.07). However, in the non-EM group, a significant increase in PRU levels was observed between days 7 and 15 (165.8 ± 57.2 vs. 223.6 ± 60.9, P = 0.002). However, 2 patients in the non-EM group (15%) showed high on-clopidogrel treatment platelet reactivity (HTPR) 2–4 h after prasugrel loading, and during the clopidogrel phase there were significant differences in the incidence of HTPR between the EM and non-EM groups. Ischemic and bleeding events were not observed during this period. In the acute phase of ACS, changing from prasugrel to clopidogrel therapy decreased the effects of suppressing platelet aggregation. However, this change was not associated with increased ischemic or bleeding events.

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Abbreviations

HTPR:

High on-clopidogrel treatment platelet reactivity

EM:

Extensive metabolizer

PM:

Poor metabolizer

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Acknowledgements

The authors would like to thank Minako Aono for her kind assistance.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Soichiro Ebisawa, Yasushi Ueki, Tomoaki Mochidome, Keisuke Senda, Hitoshi Nishimura, Tatsuya Saigusa, Takashi Miura, Hirohiko Motoki, Jun Koyama & Uichi Ikeda

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  1. Soichiro Ebisawa
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  2. Yasushi Ueki
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  3. Tomoaki Mochidome
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  4. Keisuke Senda
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  5. Hitoshi Nishimura
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  6. Tatsuya Saigusa
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  8. Hirohiko Motoki
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  9. Jun Koyama
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Correspondence to Soichiro Ebisawa.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Ebisawa, S., Ueki, Y., Mochidome, T. et al. Comparison of platelet aggregation response in switching regimen from prasugrel to clopidogrel between CYP2C19 extensive versus non-extensive metabolizers. Cardiovasc Interv and Ther 33, 277–284 (2018). https://doi.org/10.1007/s12928-017-0482-9

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  • DOI: https://doi.org/10.1007/s12928-017-0482-9

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