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
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).