Tam Chor Cheung, Kwok Janette, Wong Anthony, Yung Arthur, Shea Catherine, Kong Shun Ling, Tang Wing Hong, Siu David, Chan Raymond, Lee Stephen
1 Division of Cardiology, Queen Mary Hospital, The University of Hong Kong.
2 Division of Transplantation and Immunogenetics, Queen Mary Hospital, The University of Hong Kong.
J Int Med Res. 2017 Feb;45(1):134-146. doi: 10.1177/0300060516677190. Epub 2016 Dec 22.
Objective The CYP2C19 loss-of-function (LoF) allele is present in half of the East Asian population and is associated with high on-treatment platelet reactivity (HTPR). This study aimed to investigate whether a rapid genotyping-guided approach is feasible and efficacious for selecting P2Y12 receptor blockers in Chinese patients suffering from acute coronary syndrome (ACS). Methods This was a single-centre, prospective, randomized, open-label study. A total of 132 patients with ACS were randomized to the rapid genotyping-guided treatment group (GG, N = 65) or the standard treatment group (SG, N = 67). Patients in the GG group were genotyped by the Verigene system. Patients with the CYP2C19 LoF allele were switched to ticagrelor and all remaining patients continued on clopidogrel. The endpoints were HTPR at 24 hours after the first loading dose of clopidogrel and 1 month afterwards. Results Forty patients in the GG group switched to ticagrelor, while others continued on clopidogrel. The incidence of HTPR in the GG vs SG groups was 9.2% vs 40.3% at 24 hours and 6.5% vs 32.3% at 1 month, respectively. Rapid point-of-care genotyping showed 100% concordance with conventional genotyping by real-time polymerase chain reaction. Conclusions In Chinese patients suffering from ACS, the rapid genotyping-guided approach for selecting P2Y12 receptor blockers is feasible and reduces the incidence of HTPR. Clinical Trial Registration URL: http://clinicaltrials.gov . Unique identifier: NCT01994941.
目的 CYP2C19功能缺失（LoF）等位基因在半数东亚人群中存在，并与治疗中高血小板反应性（HTPR）相关。本研究旨在调查快速基因分型指导方法在为中国急性冠状动脉综合征（ACS）患者选择P2Y12受体阻滞剂时是否可行且有效。方法 这是一项单中心、前瞻性、随机、开放标签研究。共132例ACS患者被随机分为快速基因分型指导治疗组（GG组，N = 65）或标准治疗组（SG组，N = 67）。GG组患者通过Verigene系统进行基因分型。携带CYP2C19 LoF等位基因的患者换用替格瑞洛，其余所有患者继续使用氯吡格雷。终点为首次负荷剂量氯吡格雷后24小时及之后1个月时的HTPR。结果 GG组40例患者换用替格瑞洛，其他患者继续使用氯吡格雷。GG组与SG组HTPR的发生率在24小时时分别为9.2%对40.3%，1个月时分别为6.5%对32.3%。即时快速基因分型与通过实时聚合酶链反应的传统基因分型显示100%一致性。结论 在患有ACS的中国患者中，快速基因分型指导选择P2Y12受体阻滞剂的方法可行，并降低了HTPR的发生率。临床试验注册网址：http://clinicaltrials.gov 。唯一标识符：NCT01994941。
