Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Department of Cardiology (X.Y., J.C., J.Y., H.L., J.Q., F.H., C.S., H.Z., Y.H., J.L.), Department of Anesthesiology (H.J.), State Key Laboratory of Cardiovascular Disease; and Beijing Key Laboratory for Molecular Diagnostics of Cardiovascular Diseases, Diagnostic Laboratory Service (Z.Z., Z.L.), Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Circulation. 2018 May 22;137(21):2231-2245. doi: 10.1161/CIRCULATIONAHA.117.030190. Epub 2018 Feb 2.
Patients undergoing percutaneous coronary intervention react differently to antiplatelet drugs. Those with low responsiveness to clopidogrel have a higher risk of cardiac ischemic events. The goal of this study is to conduct a head-to-head comparison of the safety and effectiveness of intensified antiplatelet therapies (either double-dose clopidogrel [DOUBLE] or adjunctive cilostazol [TRIPLE]) and conventional strategy (STANDARD) in patients after percutaneous coronary intervention.
In this single-center, randomized, controlled trial, we used thromboelastography, a platelet function test, to select 1078 patients undergoing percutaneous coronary intervention at high thrombotic risk and compared the intensified antiplatelet therapies with standard antiplatelet therapy. The primary outcome was the incidence of major adverse cardiac and cerebrovascular events at 18 months after percutaneous coronary intervention, defined as a composite of all-cause death, myocardial infarction, target vessel revascularization, or stroke. Bleeding Academic Research Consortium defined bleeding complications (types 1, 2, 3, or 5) were the safety end points.
The primary end point occurred in 52 patients (14.4%) in the STANDARD group, 38 patients (10.6%) in the DOUBLE group, and 30 patients (8.5%) in the TRIPLE group (hazard ratio, 0.720; 95% confidence interval, 0.474-1.094, DOUBLE versus STANDARD; hazard ratio, 0.550; 95% confidence interval, 0.349-0.866, TRIPLE versus STANDARD). No significant difference in the rates of major bleeding (Bleeding Academic Research Consortium grade≥3) was found in the DOUBLE group (3.34% versus 1.93% in STANDARD, =0.133) and the TRIPLE group (2.53% versus 1.93% in STANDARD, =0.240). The rate of Bleeding Academic Research Consortium-defined minor bleeding increased in the DOUBLE group (27.4% versus 20.3% in STANDARD, =0.031), but not in the TRIPLE group (23.6% versus 20.3% in STANDARD, =0.146).
In patients with low responsiveness to clopidogrel, as measured by thromboelastography, the intensified antiplatelet strategies with adjunctive use of cilostazol significantly improved the clinical outcomes without increasing the risk of major bleeding. Decreased trend of negative outcomes could be observed in patients with double dosage of clopidogrel, but the difference was not significant.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT01779401.
接受经皮冠状动脉介入治疗的患者对抗血小板药物的反应不同。对氯吡格雷反应较低的患者发生心脏缺血事件的风险较高。本研究的目的是对头对头比较强化抗血小板治疗（双倍剂量氯吡格雷[DOUBLE]或辅助西洛他唑[TRIPLE]）与常规策略（STANDARD）在经皮冠状动脉介入治疗后的患者中的安全性和有效性。
在这项单中心、随机、对照试验中，我们使用血栓弹力图（一种血小板功能测试）选择了 1078 名高血栓风险的经皮冠状动脉介入治疗患者，并将强化抗血小板治疗与标准抗血小板治疗进行了比较。主要终点是经皮冠状动脉介入治疗后 18 个月主要不良心脑血管事件的发生率，定义为全因死亡、心肌梗死、靶血管血运重建或卒中的复合终点。出血学术研究联合会（Bleeding Academic Research Consortium，BARC）定义的出血并发症（类型 1、2、3 或 5）为安全性终点。
STANDARD 组 52 例（14.4%）、DOUBLE 组 38 例（10.6%）和 TRIPLE 组 30 例（8.5%）发生主要终点事件（风险比，0.720；95%置信区间，0.474-1.094，DOUBLE 与 STANDARD；风险比，0.550；95%置信区间，0.349-0.866，TRIPLE 与 STANDARD）。DOUBLE 组（3.34%比 STANDARD 组的 1.93%，=0.133）和 TRIPLE 组（2.53%比 STANDARD 组的 1.93%，=0.240）的主要出血（BARC 分级≥3）发生率无显著差异。DOUBLE 组（27.4%比 STANDARD 组的 20.3%，=0.031）的 Bleeding Academic Research Consortium 定义的轻微出血发生率增加，但 TRIPLE 组无此变化（23.6%比 STANDARD 组的 20.3%，=0.146）。
在经血栓弹力图测量低氯吡格雷反应的患者中，辅助使用西洛他唑的强化抗血小板策略显著改善了临床结局，而不增加大出血风险。氯吡格雷双倍剂量组患者的不良结局呈下降趋势，但差异无统计学意义。
