Influence of CYP2C19 genotypes for the effect of 1-month dual antiplatelet therapy followed by clopidogrel monotherapy r
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ORIGINAL ARTICLE
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 Hirotoshi Watanabe1 · Takeshi Morimoto2 · Manabu Ogita3 · Satoru Suwa3 · Masahiro Natsuaki4 · Nobuhiro Suematsu5 · Yorihiko Koeda6 · Yoshihiro Morino6 · Akira Nikaido7 · Yoshiki Hata7 · Masayuki Doi8 · Kiyoshi Hibi9 · Kazuo Kimura9 · Shunsuke Yoda10 · Takeo Kaneko10 · Koji Nishida11 · Kazuya Kawai11 · Koji Yamaguchi12 · Tetsuzo Wakatsuki12 · Norimasa Tonoike13 · Masashi Yamamoto13 · Shogo Shimizu14 · Takao Shimohama15 · Junya Ako15 · Takeshi Kimura1 on behalf of STOPDAPT-2 Investigators Received: 27 August 2020 / Accepted: 7 October 2020 © Japanese Association of Cardiovascular Intervention and Therapeutics 2020, corrected publication 2020
Abstract The ultra-short dual antiplatelet therapy (DAPT) followed by P 2Y12 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. Keywords Antiplatelet therapy · Coronary artery disease · Genotype · Myocardial infarction · Percutaneous coronary intervention
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12928-020-00719-6)
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