Ticagrelor Versus Clopidogrel in Black Patients With Stable Coronary Artery Disease: Prospective, Randomized, Open-Label, Multiple-Dose, Crossover Pilot Study
Ticagrelor Versus Clopidogrel in Black Patients With Stable Coronary Artery Disease: Prospective, Randomized, Open-Label, Multiple-Dose, Crossover Pilot Study
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DOI：
10.1161/circinterventions.114.002232
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发表时间：
2015-07
期刊：
影响因子：
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通讯作者：
R. Waksman;Juan Maya;D. Angiolillo;G. Carlson;R. Teng;R. Caplan;K. Ferdinand
中科院分区：
文献类型：
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作者：
R. Waksman;Juan Maya;D. Angiolillo;G. Carlson;R. Teng;R. Caplan;K. Ferdinand
背景-黑人冠状动脉疾病（CAD）的负担很高，这突出了在这一人群中进行抗血小板药物临床研究的必要性。我们试图在服用低剂量阿司匹林（乙酰水杨酸）的稳定型CAD黑人患者中评价替格瑞洛与氯吡格雷负荷和维持给药期间的血小板反应性，以及替格瑞洛及其代谢产物AR-C124910 XX的药代动力学特征。方法和结果-在一项多中心、随机、开放标签、交叉研究中，34名接受乙酰水杨酸75 - 100 mg/d治疗的稳定型CAD黑人患者随机接受氯吡格雷（600 mg，然后75 mg QD，持续7-9天）或替格瑞洛（180 mg，然后90 mg BID，持续7-9天）治疗。在洗脱期10至14天后，患者转换治疗方案。主要终点是负荷剂量后2小时的血小板反应性（通过VerifyNow测定测量的P2 Y12反应性单位[PRU]）。负荷剂量后2小时，替格瑞洛（27.6）的最小二乘平均PRU低于氯吡格雷（211.2）;最小二乘平均差异为-183.6（95%置信区间，-213.9至-153.3; P<0.001）。在所有时间点，替格瑞洛与氯吡格雷相比，最小二乘平均PRU显著较低，PRU较基线的百分比降低在统计学上更大。在给药后2小时，替格瑞洛组治疗中血小板高反应性（≥208 PRU）的发生率（0%）低于氯吡格雷组（57.1%）。替格瑞洛和AR-C124910 XX的药代动力学特征与稳定CAD人群中的先前报告一致。结论：在接受低剂量乙酰水杨酸治疗的稳定型CAD黑人患者中，替格瑞洛比氯吡格雷起效更快，血小板抑制程度更高。临床试验注册-URL：http://www.clinicaltrials.gov。唯一标识符：NCT 01523392。
Background—The burden of coronary artery disease (CAD) is high in blacks, highlighting the need for clinical research of antiplatelet agents in this population. We sought to evaluate platelet reactivity during loading and maintenance dosing of ticagrelor versus clopidogrel, and the pharmacokinetic profile of ticagrelor and its metabolite AR-C124910XX, in black patients with stable CAD taking low-dose aspirin (acetylsalicylic acid). Methods and Results—In a multicenter, randomized, open-label, crossover study, 34 blacks with stable CAD receiving acetylsalicylic acid 75 to 100 mg/d were randomized to clopidogrel (600 mg, then 75 mg QD for 7–9 days) or ticagrelor (180 mg, then 90 mg BID for 7–9 days). After washout 10 to 14 days, patients switched regimens. The primary end point was platelet reactivity 2 hours post loading dose (P2Y12 reactivity units [PRU] measured by the VerifyNow assay). Least-squares mean PRU at 2 hours post loading dose was lower with ticagrelor (27.6) versus clopidogrel (211.2); least-squares mean difference was –183.6 (95% confidence interval, –213.9 to –153.3; P<0.001). At all time points, the least-squares mean PRU was significantly lower, and the percent reduction in PRU from baseline was statistically greater, with ticagrelor versus clopidogrel. At 2 hours post dose, the prevalence of high on-treatment platelet reactivity (≥208 PRU) was lower with ticagrelor (0%) than with clopidogrel (57.1%). Pharmacokinetic profiles of ticagrelor and AR-C124910XX were consistent with previous reports in stable CAD populations. Conclusions—In black patients with stable CAD receiving low-dose acetylsalicylic acid, ticagrelor provided a faster onset and greater degree of platelet inhibition than clopidogrel. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01523392.