Division of Cardiology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
Division of Research and Innovation, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; Department of Statistics, Computer Science, Applications, Università di Firenze, Florence, Italy.
J Am Coll Cardiol. 2018 May 1;71(17):1869-1877. doi: 10.1016/j.jacc.2018.02.029. Epub 2018 Mar 11.
Although clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), its efficacy is hampered by interpatient response variability caused by genetic polymorphisms associated with clopidogrel's metabolism.
The goal of this study was to evaluate whether selecting antiplatelet therapy (clopidogrel, prasugrel, or ticagrelor) on the basis of a patient's genetic and clinical characteristics leads to better clinical outcomes compared with the standard of care, which bases the selection on clinical characteristics alone.
Patients hospitalized for ACS were randomly assigned to standard of care or the pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C192, and CYP2C1917 using an ST Q3 system that provides data within 70 min at each patient's bedside. The patients were followed up for 12 ± 1 month for the primary composite endpoint of cardiovascular death and the first occurrence of nonfatal myocardial infarction, nonfatal stroke, and major bleeding defined according to Bleeding Academic Research Consortium type 3 to 5 criteria.
After enrolling 888 patients, the study was prematurely stopped. Clopidogrel was used more frequently in the standard-of-care arm (50.7% vs. 43.3%), ticagrelor in the pharmacogenomic arm (42.6% vs. 32.7%; p = 0.02), and prasugrel was equally used in both arms. The primary endpoint occurred in 71 patients (15.9%) in the pharmacogenomic arm and in 114 (25.9%) in the standard-of-care arm (hazard ratio: 0.58; 95% confidence interval: 0.43 to 0.78; p < 0.001).
A personalized approach to selecting antiplatelet therapy for patients with ACS may reduce ischemic and bleeding events. (Pharmacogenetics of Clopidogrel in Patients With Acute Coronary Syndromes [PHARMCLO]; NCT03347435).
尽管氯吡格雷仍广泛用于急性冠状动脉综合征（ACS）患者，但由于与氯吡格雷代谢相关的遗传多态性导致个体间反应的变异性，其疗效受到了阻碍。
本研究旨在评估基于患者的遗传和临床特征选择抗血小板治疗（氯吡格雷、普拉格雷或替格瑞洛）是否比仅基于临床特征选择的标准治疗更能改善临床结局。
因 ACS 住院的患者被随机分配至标准治疗组或药物基因组组，后者包括使用 ST Q3 系统进行 ABCB1、CYP2C192 和 CYP2C1917 的基因分型，该系统可在每位患者床边 70 分钟内提供数据。患者随访 12±1 个月，主要复合终点为心血管死亡和首次发生非致命性心肌梗死、非致命性卒中和根据 Bleeding Academic Research Consortium 3 至 5 型标准定义的大出血。
在纳入 888 例患者后，研究提前终止。标准治疗组更常使用氯吡格雷（50.7% vs. 43.3%），药物基因组组更常使用替格瑞洛（42.6% vs. 32.7%；p=0.02），普拉格雷在两组中的使用比例相当。药物基因组组有 71 例（15.9%）患者发生主要终点事件，标准治疗组有 114 例（25.9%）患者发生（风险比：0.58；95%置信区间：0.43 至 0.78；p<0.001）。
对 ACS 患者进行个体化的抗血小板治疗选择可能会减少缺血和出血事件。（氯吡格雷在急性冠状动脉综合征患者中的药物基因组学[PHARMCLO]；NCT03347435）。
