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Influence of CYP2C19 genotypes for the effect of 1-month dual antiplatelet therapy followed by clopidogrel monotherapy relative to 12-month dual antiplatelet therapy on clinical outcomes after percutaneous coronary intervention: a genetic substudy from the STOPDAPT-2

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Abstract

The ultra-short dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy might be promising after percutaneous coronary intervention (PCI). However, CYP2C19 loss-of-function (LOF) alleles have been reported to diminish the effect of clopidogrel, and clopidogrel monotherapy has a concern about the increased ischemic risk for patients with such alleles. STOPDAPT-2 is the multicenter prospective open-label, but adjudicator-blinded randomized control study comparing 1-month DAPT followed by clopidogrel monotherapy with the standard 12-month DAPT after PCI with cobalt–chromium everolimus-eluting stents. Among the participants of STOPDAPT-2, selected patients participated in a substudy of the CYP2C19 gene test. Patients with two CYP2C19*2 or *3 alleles were defined as the poor metabolizer (PM), one allele as the intermediate metabolizer (IM), and no allele as the extensive metabolizer (EM). The primary endpoint was the composite of cardiovascular and bleeding events, as defined in STOPDAPT-2. Among 750 (24.9%) patients with known CYP2C19 genotypes, 129 (17.2%) were PM, 367 (49.0%) were IM, and 254 (33.9%) were EM. The hazard ratios of 1-month DAPT relative to 12-month DAPT for the primary endpoint in PM, IM, and EM strata were 0.66 (95% CI 0.11–3.94), 1.94 (95% CI 0.60–6.31), and 0.21 (95% CI 0.02–1.78), respectively (P interaction = 0.17), and those for cardiovascular composite endpoint were 1.00 (95% CI 0.14–7.10), 6.10 (95% CI 0.75–49.55), and 0.26 (95% CI 0.03–2.34), respectively (P interaction = 0.12). In conclusion, for the selected patients in STOPDAPT-2 trial, CYP2C19 LOF alleles had no significant, consistent interaction with the effect of 1-month DAPT relative to 12-month DAPT for clinical outcomes, although the study was overtly underpowered.

Trial registry

STOPDAPT-2 ClinicalTrials.gov number, NCT02619760.

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Acknowledgements

We appreciated the members of the Research Institute for Production Development for the management of the large clinical trials and the data collection.

Funding

Funded by Abbott Vascular Japan.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Hirotoshi Watanabe & Takeshi Kimura

  2. Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan

    Takeshi Morimoto

  3. Department of Cardiovascular Medicine, Juntendo University Shizuoka Hospital, Izunokuni, Japan

    Manabu Ogita & Satoru Suwa

  4. Department of Cardiovascular Medicine, Saga University, Saga, Japan

    Masahiro Natsuaki

  5. Department of Cardiovascular Medicine, Saiseikai Fukuoka General Hospital, Fukuoka, Japan

    Nobuhiro Suematsu

  6. Division of Cardiology, Department of Internal Medicine, Memorial Heart Center, Iwate Medical University, Morioka, Japan

    Yorihiko Koeda & Yoshihiro Morino

  7. Department of Cardiology, Minamino Cardiovascular Hospital, Hachioji, Japan

    Akira Nikaido & Yoshiki Hata

  8. Department of Cardiology, Kagawa Prefectural Central Hospital, Takamatsu, Japan

    Masayuki Doi

  9. Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan

    Kiyoshi Hibi & Kazuo Kimura

  10. Department of Internal Medicine, Division of Cardiology, Shimonoseki City Hospital, Shimonoseki, Japan

    Shunsuke Yoda & Takeo Kaneko

  11. Department of Cardiology, Chikamori Hospital, Kochi, Japan

    Koji Nishida & Kazuya Kawai

  12. Department of Cardiovascular Medicine, Tokushima University Hospital, Tokushima, Japan

    Koji Yamaguchi & Tetsuzo Wakatsuki

  13. Department of Cardiology, Kimitsu Chuo Hospital, Kisarazu, Japan

    Norimasa Tonoike & Masashi Yamamoto

  14. Department of Cardiology, Mashiko Hospital, Kawaguchi, Japan

    Shogo Shimizu

  15. Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan

    Takao Shimohama & Junya Ako

Authors
  1. Hirotoshi Watanabe
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STOPDAPT-2 Investigators

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Correspondence to Takeshi Kimura.

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Conflict of interest

STOPDAPT-2 is funded by Abbott Vascular Japan. Junya Ako receives lecture fees from Abbott Vascular Japan, Sanofi, Daiichi-Sankyo, and AstraZeneca. Takeshi Kimura serves as an advisory role to Abbott Vascular Japan and received a research grant from Daiichi-Sankyo. Others have no conflict of interests.

IRB information

The STOPDAPT-2 was approved by Kyoto University Certified Review Board (Reference number; YC1114). The STOPDAPT-2 genotype substudy was approved by Kyoto University Graduate School of Medicine, Ethics Committee (Reference number; G0781).

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Watanabe, H., Morimoto, T., Ogita, M. et al. Influence of CYP2C19 genotypes for the effect of 1-month dual antiplatelet therapy followed by clopidogrel monotherapy relative to 12-month dual antiplatelet therapy on clinical outcomes after percutaneous coronary intervention: a genetic substudy from the STOPDAPT-2. Cardiovasc Interv and Ther 36, 403–415 (2021). https://doi.org/10.1007/s12928-020-00719-6

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