Impact of CYP2C19 polymorphisms on the antiplatelet effect of clopidogrel in an actual clinical setting in Japan

Toshikazu Jinnai, Hisanori Horiuchi, Takeru Makiyama, Junichi Tazaki, Tomohisa Tada, Masaharu Akao, Koh Ono, Kozo Hoshino, Yumiko Naruse, Kanako Takahashi, Haruyo Watanabe, Toru Kita, Takeshi Kimura

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

Abstract

Background: The P2Y12 adenosine diphosphate (ADP) receptor blocker, clopidogrel, an essential drug for the prevention of stent thrombosis after percutaneous coronary intervention (PCI), is a prodrug that requires CYP2C19-and CYP3A4-mediating activation. CYP2C19*2 and *3 polymorphisms are known to lack enzymatic activity. CYP2C19 polymorphisms have been reported to exhibit weaker antiplatelet response to clopidogrel in healthy subjects. The effect of polymorphisms of CYP2C19, CYP3A4 and P2Y12 on the antiplatelet effect of clopidogrel in clinical patients was examined in the present study. Methods and Results: Single nucleotide polymorphisms of CYP2C19*2, *3, CYP3A4 (IVS10+12G>A) and P2Y12 (T744C) were determined in 25 PCI-scheduled patients who had been systematically analyzed for the antiplatelet effect of clopidogrel in a previous study. On the basis of CYP2C19 genotype, 11 patients (44%) were classified as extensive metabolizers (EMs), 8 (32%) as intermediate metabolizers (IMs) and 6 (24%) as poor metabolizers (PMs). The rates of inhibition of 5 μmol/L ADP-induced platelet aggregation by clopidogrel intake at 48 h were 31.6±14.3% in EMs, 18.4±10.0% in IMs (P=0.04 vs EMs) and 16.0±13.0% in PMs (P=0.02 vs EMs). Conclusions: CYP2C19 polymorphisms are frequent in Japanese, and the antiplatelet effect of clopidogrel is strongly affected by them in the real-world clinical setting.

Original languageEnglish
Pages (from-to)1498-1503
Number of pages6
JournalCirculation Journal
Volume73
Issue number8
DOIs
Publication statusPublished - 2009 Aug

Keywords

  • Antiplatelet therapy
  • Clopidogrel
  • Polymorphisms
  • Stent
  • Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Impact of CYP2C19 polymorphisms on the antiplatelet effect of clopidogrel in an actual clinical setting in Japan'. Together they form a unique fingerprint.

Cite this