Teal Philip A
Division of Neurology, University of British Columbia, Vancouver, Canada.
Cerebrovasc Dis. 2004;17 Suppl 3:6-10. doi: 10.1159/000075298.
Dual antiplatelet therapy that inhibits more than one pathway of platelet activation is appealing and biologically rational. The CURE study evaluated the efficacy and safety of clopidogrel on top of acetylsalicylic acid (ASA) versus standard therapy (including ASA) in over 12,000 patients with unstable angina or non-ST-segment elevation myocardial infarction (MI). Clopidogrel in combination with ASA reduced the relative risk of the combined atherothrombotic endpoint of cardiovascular death, MI or stroke by 20% (95% CI 0.72-0.90; p < 0.001) and the absolute risk of this composite endpoint by 2.1%. While the study was not powered or designed to demonstrate a reduction in stroke, there was a 14% reduction in stroke risk (p > 0.05). Dual antiplatelet therapy was associated with an acceptable 1% increase in the incidence of major bleeding events (p = 0.001). PCI-CURE, a prespecified substudy of patients who underwent percutaneous coronary intervention (PCI) during CURE, confirmed the early and sustained benefits of clopidogrel therapy seen in the overall CURE study. CREDO was a randomized, double-blind, placebo-controlled trial in more than 2,100 patients that evaluated the continuation of clopidogrel on top of standard therapy including ASA for 12 months after PCI, and the benefit of a preprocedural clopidogrel loading dose. The long-term results at 1 year showed that there was a 27% reduction in the risk of stroke, MI or death with long-term clopidogrel therapy (p = 0.02). There was a consistent benefit of extended clopidogrel therapy for each component of the composite endpoint, with a 25.1% relative risk reduction for all-cause stroke. In patients who received clopidogrel > or =6 h before PCI, there was a 39% reduction in the risk of death, MI or urgent target-vessel revascularization at 28 days (p = 0.051). These data suggest important implications in the future for the use of an early loading dose of clopidogrel in patients undergoing carotid stenting and, if proven in current or future trials, the use of a loading dose followed by long-term continuation of clopidogrel in other high-risk atherothrombotic patients such as those with transient ischaemic attack or ischaemic stroke.
抑制血小板激活的多条途径的双重抗血小板治疗具有吸引力且符合生物学原理。CURE研究评估了在12000多名不稳定型心绞痛或非ST段抬高型心肌梗死（MI）患者中，氯吡格雷联合阿司匹林（ASA）对比标准治疗（包括ASA）的疗效和安全性。氯吡格雷联合ASA使心血管死亡、MI或中风的联合动脉粥样硬化血栓形成终点的相对风险降低了20%（95%CI 0.72 - 0.90；p < 0.001），该复合终点的绝对风险降低了2.1%。虽然该研究未设计用于证明中风风险降低，但中风风险降低了14%（p > 0.05）。双重抗血小板治疗与主要出血事件发生率可接受的1%增加相关（p = 0.001）。PCI - CURE是CURE研究中对接受经皮冠状动脉介入治疗（PCI）患者的一项预先设定的子研究，证实了在整个CURE研究中观察到的氯吡格雷治疗的早期和持续益处。CREDO是一项针对2100多名患者的随机、双盲、安慰剂对照试验，评估了PCI后在包括ASA的标准治疗基础上氯吡格雷持续应用12个月的情况，以及术前氯吡格雷负荷剂量的益处。1年的长期结果显示，长期氯吡格雷治疗使中风、MI或死亡风险降低了27%（p = 0.02）。氯吡格雷延长治疗对复合终点的每个组成部分都有持续益处，全因中风的相对风险降低了25.1%。在PCI前6小时或更长时间接受氯吡格雷治疗的患者中，28天时死亡、MI或紧急靶血管血运重建的风险降低了39%（p = 0.051）。这些数据表明，未来对于接受颈动脉支架置入术的患者使用氯吡格雷早期负荷剂量具有重要意义，并且如果在当前或未来试验中得到证实，对于其他高危动脉粥样硬化血栓形成患者，如短暂性脑缺血发作或缺血性中风患者，使用负荷剂量后长期持续应用氯吡格雷也具有重要意义。
