Effects of genetic variants on platelet reactivity and one-year clinical outcomes after percutaneous coronary intervention: A prospective multicentre registry study

• Published in: Scientific reports Vol. 8; no. 1; pp. 1229 - 9
• Main Authors: Joo, Hyung Joon, Ahn, Sung Gyun, Park, Jae Hyoung, Park, Ji Young, Hong, Soon Jun, Kim, Seok-Yeon, Choi, WoongGil, Gwon, HyeonCheol, Lim, Young-Hyo, Kim, Weon, Kang, Woong Chol, Cho, Yun-Hyeong, Kim, Yong Hoon, Yoon, JungHan, Shin, WonYong, Hong, Myeong-Ki, Garg, Scot, Jang, Yangsoo, Lim, Do-Sun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.01.2018; Nature Publishing Group
• Subjects: 45/23; 631/208/2489/144; 692/4019/2776; Aged; Angioplasty; Aryldialkylphosphatase - genetics; ATP Binding Cassette Transporter, Subfamily B - genetics; Bleeding; Cerebral infarction; Clinical outcomes; Clopidogrel; Cytochrome P-450 CYP2C19 - genetics; Cytochrome P-450 CYP2C9 - genetics; Death; Drug delivery; Female; Gene polymorphism; Genetic diversity; Genetic variance; Heart diseases; Humanities and Social Sciences; Humans; Implants; Male; Middle Aged; Mortality; multidisciplinary; Myocardial infarction; Percutaneous Coronary Intervention - adverse effects; Percutaneous Coronary Intervention - methods; Platelet Aggregation; Platelet Aggregation Inhibitors - adverse effects; Platelets; Polymorphism, Single Nucleotide; Postoperative Complications - etiology; Postoperative Complications - genetics; Receptors, Purinergic P2Y12 - genetics; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Stents; Thromboembolism; Thrombosis; Thrombosis - etiology; Thrombosis - genetics; Ticlopidine - adverse effects; Ticlopidine - analogs & derivatives
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-18134-y

Clopidogrel is the mainstay for antiplatelet treatment after percutaneous coronary intervention (PCI). The relationship of platelet reactivity and genetic polymorphism with clinical outcomes with newer-generation drug-eluting stents is unclear. We analysed 4,587 patients for the most powerful single-nucleotide polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment platelet reactivity (OPR). The optimal cut-off value of high OPR for major adverse thrombotic events was 266. CYP2C19 was significantly associated with high OPR and the number of CYP2C19*R (*2 or *3) alleles was proportional to the increased risk of high OPR. Death, myocardial infarction (MI), stroke, stent thrombosis, and bleeding events were assessed during a 1-year follow-up period. Primary endpoints were death and non-fatal MI. The cumulative 1-year incidence of death and stent thrombosis was significantly higher in patients with CYP2C19*2/*2, CYP2C19*2/*3, and CYP2C19*3/*3 (Group 3) than in patients with CYP2C19*1/*1 (Group 1). Multivariate Cox proportional hazard model showed that cardiac death risk was significantly higher in Group 3 than in Group 1 (hazard ratio 2.69, 95% confidence interval 1.154–6.263, p = 0.022). No association was reported between bleeding and OPR. Thus, CYP2C19 may exert a significant impact on the prognosis of PCI patients even in the era of newer-generation drug-eluting stents.