Xiao-Fang Tang1, Ya-Ling Han2, Jia-Hui Zhang3, Jing Wang3, Yi Yao3, Chen He3, Bo Xu1, Zhan Gao1, Shu-Bin Qiao1, Jue Chen1, Yuan Wu1, Ji-Lin Chen1, Run-Lin Gao1, Yue-Jin Yang4, Jin-Qing Yuan5. 1. State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. 2. Department of Cardiology, Institute of Cardiovascular Research of People's Liberation Army, Shenyang Northern Hospital, Shenyang, Liaoning 110840, China. 3. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. 4. State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. Electronic address: dr_yuejinyang@126.com. 5. State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. Electronic address: dr_jinqingyuan@126.com.
Abstract
INTRODUCTION: Both CYP2C19 genotyping and platelet function testing are used to predict major adverse cardiac events (MACEs) in Chinese patients treated with clopidogrel and undergoing stent implantation, but the most accurate prognostic technique is still debated. Here, we combine both techniques, to determine if a more accurate prognosis is possible. METHODS: Patients undergoing stent implantation (1104) were genotyped and assessed for platelet reactivity, with a 12-month follow-up. The CYP2C19*2 (rs4244285), and *3 (rs4986893) alleles were genotyped. High on treatment platelet reactivity was defined as adenosine diphosphate (ADP)-induced platelet inhibition ≤30%. MACEs included death, nonfatal myocardial infarction, target vessel revascularization, or stent thrombosis. RESULTS AND CONCLUSIONS: Hazard ratios (HRs) for cardiovascular ischemic outcomes based on the two testing methods are as follows. CYP2C19 genotyping: carriers of CYP2C19 loss-of-function alleles, HR: 2.515, 95% confidence interval (CI), 1.150-5.501, P=0.021; ADP-induced platelet inhibition ≤30%, HR: 1.992, 95% CI, 1.040-3.818, P=0.038. An ischemic risk score between zero and two was calculated. Compared with the group with a score of zero, HRs for adverse cardiovascular outcomes were 4.078 for those with a score of two (95% CI: 1.525-10.905, P=0.005). However, there was no significant difference between the group with the score of zero and the group with the score of one. CYP2C19 genotyping combined with platelet reactivity is an independent and additive predictor of 1-year MACE in Chinese patients undergoing stenting with clopidogrel treatment, which is better than either test alone.
INTRODUCTION: Both CYP2C19 genotyping and platelet function testing are used to predict major adverse cardiac events (MACEs) in Chinese patients treated with clopidogrel and undergoing stent implantation, but the most accurate prognostic technique is still debated. Here, we combine both techniques, to determine if a more accurate prognosis is possible. METHODS:Patients undergoing stent implantation (1104) were genotyped and assessed for platelet reactivity, with a 12-month follow-up. The CYP2C19*2 (rs4244285), and *3 (rs4986893) alleles were genotyped. High on treatment platelet reactivity was defined as adenosine diphosphate (ADP)-induced platelet inhibition ≤30%. MACEs included death, nonfatal myocardial infarction, target vessel revascularization, or stent thrombosis. RESULTS AND CONCLUSIONS: Hazard ratios (HRs) for cardiovascular ischemic outcomes based on the two testing methods are as follows. CYP2C19 genotyping: carriers of CYP2C19 loss-of-function alleles, HR: 2.515, 95% confidence interval (CI), 1.150-5.501, P=0.021; ADP-induced platelet inhibition ≤30%, HR: 1.992, 95% CI, 1.040-3.818, P=0.038. An ischemic risk score between zero and two was calculated. Compared with the group with a score of zero, HRs for adverse cardiovascular outcomes were 4.078 for those with a score of two (95% CI: 1.525-10.905, P=0.005). However, there was no significant difference between the group with the score of zero and the group with the score of one. CYP2C19 genotyping combined with platelet reactivity is an independent and additive predictor of 1-year MACE in Chinese patients undergoing stenting with clopidogrel treatment, which is better than either test alone.
Authors: Yu Ueda; Ronald H L Li; Nghi Nguyen; Eric S Ontiveros; Samantha L Kovacs; Maureen S Oldach; Karen M Vernau; Michael H Court; Joshua A Stern Journal: Sci Rep Date: 2021-06-15 Impact factor: 4.379