Isshiki Takaaki, Kimura Takeshi, Ueno Takafumi, Nakamura Masato, Igarashi Keiichi, Yokoi Hiroyoshi, Kobayashi Masahiko, Ikari Yuji
Division of Cardiology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Int Heart J. 2012;53(2):91-101. doi: 10.1536/ihj.53.91.
Clopidogrel in combination with aspirin has been widely used in patients who have undergone coronary stent implantation. However, the benefit to Japanese patients with stable angina (SA) or old myocardial infarction (OMI) undergoing percutaneous coronary intervention (PCI) still remains unclear.The aim of this multicenter, randomized, double-blind, clinical study was to evaluate the safety of a clopidogrel 300 mg loading dose followed by a 75 mg maintenance dose compared to ticlopidine 100 mg twice daily in patients with SA or OMI undergoing PCI who were on aspirin (81 to 100 mg once daily). The primary endpoint was the composite of safety events comprising clinically significant bleeding, blood disorders, elevated liver function values, and study drug discontinuation up to week 12. The key secondary endpoints were major adverse cardiac events (MACE), major adverse cardiac and cerebrovascular events (MACCE), and bleeding events. A total of 1003 patients were randomly allocated to receive either clopidogrel or ticlopidine and 931 patients underwent PCI. The cumulative incidence of the composite safety endpoint in the clopidogrel group was statistically lower than that of ticlopidine (P < 0.0001, hazard ratio; 0.259; 95%CI; 0.187 to 0.359). There were no statistically significant differences between treatments with respect to MACE at week 12 (P = 0.7899) nor to the bleeding events (P = 0.5292, stratified log-rank test).Clopidogrel was found to have a better benefit/risk profile than ticlopidine in Japanese patients with SA or OMI undergoing PCI.
氯吡格雷联合阿司匹林已广泛应用于接受冠状动脉支架植入术的患者。然而，对于接受经皮冠状动脉介入治疗（PCI）的日本稳定型心绞痛（SA）或陈旧性心肌梗死（OMI）患者，其益处仍不明确。本多中心、随机、双盲临床研究的目的是评估在接受PCI且每日服用阿司匹林（81至100毫克）的SA或OMI患者中，与每日两次服用100毫克噻氯匹定相比，氯吡格雷300毫克负荷剂量继以75毫克维持剂量的安全性。主要终点是包括具有临床意义的出血、血液系统疾病、肝功能值升高以及直至第12周停用研究药物在内的安全性事件的复合终点。关键次要终点是主要不良心脏事件（MACE）、主要不良心脑血管事件（MACCE）和出血事件。共有1003例患者被随机分配接受氯吡格雷或噻氯匹定治疗，931例患者接受了PCI。氯吡格雷组复合安全性终点的累积发生率在统计学上低于噻氯匹定组（P < 0.0001，风险比；0.259；95%CI；0.187至0.359）。在第12周时，治疗组之间在MACE方面（P = 0.7899）以及出血事件方面（P = 0.5292，分层对数秩检验）均无统计学显著差异。研究发现，对于接受PCI的日本SA或OMI患者，氯吡格雷的获益/风险比优于噻氯匹定。
