Ohman E M, Kleiman N S, Gacioch G, Worley S J, Navetta F I, Talley J D, Anderson H V, Ellis S G, Cohen M D, Spriggs D, Miller M, Kereiakes D, Yakubov S, Kitt M M, Sigmon K N, Califf R M, Krucoff M W, Topol E J
Duke University Medical Center, Durham, NC 27710, USA.
Circulation. 1997 Feb 18;95(4):846-54. doi: 10.1161/01.cir.95.4.846.
Platelet activation and aggregation may be key components of thrombolytic failure to restore and maintain perfusion in acute myocardial infarction. We performed a placebo-controlled, dose-ranging trial of Integrilin, a potent inhibitor of platelet aggregation, with heparin, aspirin, and accelerated alteplase.
We assigned 132 patients in a 2:1 ratio to receive a bolus and continuous infusion of one of six Integrilin doses or placebo. Another 48 patients were randomized in a 3:1, double-blind fashion to receive the highest Integrilin dose from the first phase or placebo. All patients received accelerated alteplase, aspirin, and intravenous heparin infusion; all but two groups also received an intravenous heparin bolus. The highest Integrilin dose group from the nonrandomized phase and the randomized patients were pooled for analysis and compared with placebo-treated patients. The primary end point was Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow at 90-minute angiography. Secondary end points were time to ST-segment recovery, an in-hospital composite (death, reinfarction, stroke, revascularization procedures, new heart failure, or pulmonary edema), and bleeding variables. The highest Integrilin dose groups had more complete reperfusion (TIMI grade 3 flow, 66% versus 39% for placebo-treated patients; P = .006) and a shorter median time to ST-segment recovery (65 versus 116 minutes for placebo; P = .05). The groups had similar rates of the composite end point (43% versus 42% for placebo-treated patients) and severe bleeding (4% versus 5%, respectively).
The incidence and speed of reperfusion can be enhanced when a potent inhibitor of the glycoprotein IIb/IIIa integrin receptor, such as Integrilin, is combined with accelerated alteplase, aspirin, and intravenous heparin.
血小板激活和聚集可能是急性心肌梗死溶栓治疗未能恢复和维持灌注的关键因素。我们开展了一项使用强效血小板聚集抑制剂依替巴肽联合肝素、阿司匹林及加速型阿替普酶的安慰剂对照、剂量范围试验。
我们将132例患者按2:1的比例分配，分别接受六种依替巴肽剂量之一的静脉推注及持续输注或安慰剂。另外48例患者以3:1的比例进行双盲随机分组，接受第一阶段最高依替巴肽剂量或安慰剂。所有患者均接受加速型阿替普酶、阿司匹林及静脉肝素输注；除两组外，其他组均接受静脉肝素推注。将非随机阶段的最高依替巴肽剂量组与随机分组的患者合并进行分析，并与接受安慰剂治疗的患者进行比较。主要终点为90分钟血管造影时的心肌梗死溶栓（TIMI）3级血流。次要终点包括ST段恢复时间、院内综合指标（死亡、再梗死、卒中、血管重建术、新发心力衰竭或肺水肿）及出血变量。最高依替巴肽剂量组的再灌注更完全（TIMI 3级血流，安慰剂治疗患者为39%，依替巴肽组为66%；P = 0.006），ST段恢复的中位时间更短（安慰剂组为116分钟，依替巴肽组为65分钟；P = 0.05）。两组的综合终点发生率相似（安慰剂治疗患者为42%，依替巴肽组为43%），严重出血发生率也相似（分别为5%和4%）。
当糖蛋白IIb/IIIa整合素受体的强效抑制剂（如依替巴肽）与加速型阿替普酶、阿司匹林及静脉肝素联合使用时，再灌注的发生率及速度可得到提高。
