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JACC-Cardiovasc. Interv., 2023 Apr 10;16(7):829-843 | https://doi.org/10.1016/j.jcin.2023.01.363 Clinical Impact of CYP2C19 Genotype on Clopidogrel-Based Antiplatelet Therapy After Percutaneous Coronary Intervention

Seung Hun Lee MD, PhD^a,b∗, Young-Hoon Jeong MD, PhD^c∗, David Hong MD ^b, Ki Hong Choi MD, PhD ^b, Joo Myung Lee MD, MPH, PhD ^b, Taek Kyu Park MD, PhD ^b, Jeong Hoon Yang MD, PhD ^b, Joo-Yong Hahn MD, PhD ^b, Seung-Hyuck Choi MD, PhD ^b, Hyeon-Cheol Gwon MD, PhD ^b, Myung Ho Jeong MD, PhD ^a, Byeong-Keuk Kim MD, PhD ^d, Hyung Joon Joo MD, PhD ^e, Kiyuk Chang MD, PhD ^f, Yongwhi Park MD, PhD ^g,h, Sung Gyun Ahn MD, PhD ⁱ, Jung-Won Suh MD, PhD ^j,k, Sang Yeub Lee MD, PhD ^c, Jung Rae Cho MD, PhD ^l, Ae-Young Her MD, PhD ^m, Hyo-Soo Kim MD, PhD ⁿ, Moo Hyun Kim MD, PhD ^o, Do-Sun Lim MD, PhD ^e, Eun-Seok Shin MD, PhD ^p, Young Bin Song MD, PhD bon behalf of thePTRG-DES Registry Investigators

^aDivision of Cardiology, Department of Internal Medicine, Heart Center, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, South Korea
^bDivision of Cardiology, Department of Internal Medicine, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
^cDivision of Cardiology, Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Chung-Ang University College of Medicine, Gwangmyeong, South Korea
^dSeverance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, South Korea
^eDepartment of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Korea University College of Medicine, Seoul, South Korea
^fDivision of Cardiology, Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, South Korea
^gDepartment of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, South Korea
^hCardiovascular Center, Gyeongsang National University Changwon Hospital, Changwon, South Korea
ⁱDepartment of Cardiology, Yonsei University Wonju Severance Christian Hospital, Wonju, South Korea
^jDepartment of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
^kDepartment of Cardiology, Seoul National University Bundang Hospital, Seongnam, South Korea
^lCardiology Division, Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, South Korea
^mDivision of Cardiology, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea
ⁿDepartment of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea
^oDepartment of Cardiology, Dong-A University Hospital, Busan, South Korea
^pDivision of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea

^∗Drs Lee and Jeong contributed equally to this work.
Address for correspondence: Dr Young Bin Song

Abstract

Background: Although there is a growing body of evidence that CYP2C19 genotyping can be beneficial when considering treatment with clopidogrel after percutaneous coronary intervention (PCI), whether a genotype-guided strategy can be generally adopted in routine practice remains unclear among East Asians.

Objectives: This study sought to investigate long-term outcomes of patients undergoing clopidogrel-based antiplatelet therapy after drug-eluting stent (DES) implantation according to CYP2C19 genotypes.

Methods: From the nationwide multicenter PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) consortium, patients who underwent CYP2C19 genotyping were selected and classified according to CYP2C19 loss-of-function allele: rapid metabolizers (RMs) or normal metabolizers (NMs) vs intermediate metabolizers (IMs) or poor metabolizers (PMs). The primary outcome was a composite of cardiac death, myocardial infarction, and stent thrombosis at 5 years after the index procedure.

Results: Of 8,163 patients with CYP2C19 genotyping, 56.7% presented with acute coronary syndrome. There were 3,098 (37.9%) in the RM or NM group, 3,906 (47.9%) in the IM group, and 1,159 (14.2%) in the PM group. IMs or PMs were associated with an increased risk of 5-year primary outcome compared with RMs or NMs (HRadj: 1.42; 95% CI: 1.01-1.98; P = 0.041), and the effect was more pronounced in the first year (HRadj: 1.67; 95% CI: 1.10-2.55; P = 0.016). The prognostic implication of being an IM and PM was significant in acute coronary syndrome patients (HRadj: 1.88; 95% CI: 1.20-2.93; P = 0.005) but not in those with stable angina (HRadj: 0.92; 95% CI: 0.54-1.55; P = 0.751) (interaction P = 0.028).

Conclusions: Among East Asians with clopidogrel-based antiplatelet therapy after DES implantation, CYP2C19 genotyping could stratify patients who were likely to have an increased risk of atherothrombotic events. (Platelet Function and genoType-Related Long-term progGosis in DES-treated Patients: A Consortium From Multi-centered Registries [PTRG-DES]; NCT04734028).

논문정보

형식Research article
게재일2023년 04월 (BRIC 등록일 2023-04-18)
연구진국내 연구진
분야 의약학 > 응용의학

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