Scripps Clinic, La Jolla, California, USA.
JAMA. 2011 Mar 16;305(11):1097-105. doi: 10.1001/jama.2011.290.
High platelet reactivity while receiving clopidogrel has been linked to cardiovascular events after percutaneous coronary intervention (PCI), but a treatment strategy for this issue is not well defined.
To evaluate the effect of high-dose compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity after PCI.
DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, active-control trial (Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety [GRAVITAS]) of 2214 patients with high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents at 83 centers in North America between July 2008 and April 2010.
High-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily) for 6 months.
The primary end point was the 6-month incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. A key pharmacodynamic end point was the rate of persistently high on-treatment reactivity at 30 days.
At 6 months, the primary end point had occurred in 25 of 1109 patients (2.3%) receiving high-dose clopidogrel compared with 25 of 1105 patients (2.3%) receiving standard-dose clopidogrel (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58-1.76; P = .97). Severe or moderate bleeding was not increased with the high-dose regimen (15 [1.4%] vs 25 [2.3%], HR, 0.59; 95% CI, 0.31-1.11; P = .10). Compared with standard-dose clopidogrel, high-dose clopidogrel provided a 22% (95% CI, 18%-26%) absolute reduction in the rate of high on-treatment reactivity at 30 days (62%; 95% CI, 59%-65% vs 40%; 95% CI, 37%-43%; P < .001).
Among patients with high on-treatment reactivity after PCI with drug-eluting stents, the use of high-dose clopidogrel compared with standard-dose clopidogrel did not reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis.
clinicaltrials.gov Identifier: NCT00645918.
经皮冠状动脉介入治疗（PCI）后氯吡格雷高反应性与心血管事件相关，但针对这一问题的治疗策略尚未明确。
评估高剂量与标准剂量氯吡格雷在 PCI 后高反应性患者中的疗效。
设计、地点和患者：这是一项在北美 83 个中心的 2214 例患者中进行的随机、双盲、阳性对照试验（Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety [GRAVITAS]），这些患者在 PCI 后 12 至 24 小时内接受药物洗脱支架治疗，且存在高反应性。
高剂量氯吡格雷（初始剂量 600mg，此后每日 150mg）或标准剂量氯吡格雷（无额外负荷剂量，每日 75mg），治疗 6 个月。
主要终点是 6 个月时心血管原因死亡、非致死性心肌梗死或支架血栓形成的发生率。主要安全性终点是根据全球溶栓和组织型纤溶酶原激活剂治疗闭塞性冠状动脉（GUSTO）定义的严重或中度出血。主要药效学终点是 30 天时持续高反应性的发生率。
在 6 个月时，高剂量氯吡格雷组有 25 例（2.3%）患者发生主要终点事件，而标准剂量氯吡格雷组有 25 例（2.3%）患者发生该事件（风险比[HR]，1.01；95%置信区间[CI]，0.58-1.76；P=.97）。高剂量方案并未增加严重或中度出血（高剂量组 15 例[1.4%]，标准剂量组 25 例[2.3%]，HR，0.59；95% CI，0.31-1.11；P=.10）。与标准剂量氯吡格雷相比，高剂量氯吡格雷使 30 天时高反应性的发生率绝对降低了 22%（95% CI，18%-26%）（62%；95% CI，59%-65%比 40%；95% CI，37%-43%；P <.001）。
在接受药物洗脱支架 PCI 后存在高反应性的患者中，与标准剂量氯吡格雷相比，使用高剂量氯吡格雷并未降低心血管原因死亡、非致死性心肌梗死或支架血栓形成的发生率。
clinicaltrials.gov 标识符：NCT00645918。
