Topol E J, Moliterno D J, Herrmann H C, Powers E R, Grines C L, Cohen D J, Cohen E A, Bertrand M, Neumann F J, Stone G W, DiBattiste P M, Demopoulos L
Department of Cardiology, Cleveland Clinic Foundation, OH 44195, USA.
N Engl J Med. 2001 Jun 21;344(25):1888-94. doi: 10.1056/NEJM200106213442502.
In the setting of percutaneous coronary revascularization, agents in the class known as platelet glycoprotein IIb/IIIa inhibitors have significantly reduced the incidence of death or nonfatal myocardial infarction at 30 days. We assessed whether there are differences in safety or efficacy between two such inhibitors, tirofiban and abciximab.
Using a double-blind, double-dummy design at 149 hospitals in 18 countries, we randomly assigned patients to receive either tirofiban or abciximab before undergoing percutaneous coronary revascularization with the intent to perform stenting. The primary end point was a composite of death, nonfatal myocardial infarction, or urgent target-vessel revascularization at 30 days. The trial was designed and statistically powered to demonstrate the noninferiority of tirofiban as compared with abciximab.
The primary end point occurred more frequently among the 2398 patients in the tirofiban group than among the 2411 patients in the abciximab group (7.6 percent vs. 6.0 percent; hazard ratio, 1.26; one-sided 95 percent confidence interval of 1.51, demonstrating lack of equivalence, and two-sided 95 percent confidence interval of 1.01 to 1.57, demonstrating the superiority of abciximab over tirofiban; P=0.038). The magnitude and the direction of the effect were similar for each component of the composite end point (hazard ratio for death, 1.21; hazard ratio for myocardial infarction, 1.27; and hazard ratio for urgent target-vessel revascularization, 1.26), and the difference in the incidence of myocardial infarction between the tirofiban group and the abciximab group was significant (6.9 percent and 5.4 percent, respectively; P=0.04). The relative benefit of abciximab was consistent regardless of age, sex, the presence or absence of diabetes, or the presence or absence of pretreatment with clopidogrel. There were no significant differences in the rates of major bleeding complications or transfusions, but tirofiban was associated with a lower rate of minor bleeding episodes and thrombocytopenia.
Although the trial was intended to assess the noninferiority of tirofiban as compared with abciximab, the findings demonstrated that tirofiban offered less protection from major ischemic events than did abciximab.
在经皮冠状动脉血运重建术中，血小板糖蛋白IIb/IIIa抑制剂类药物已显著降低了30天时死亡或非致命性心肌梗死的发生率。我们评估了替罗非班和阿昔单抗这两种此类抑制剂在安全性或疗效方面是否存在差异。
采用双盲、双模拟设计，在18个国家的149家医院，我们将患者随机分配接受替罗非班或阿昔单抗治疗，这些患者拟接受经皮冠状动脉血运重建术并打算进行支架置入。主要终点是30天时死亡、非致命性心肌梗死或紧急靶血管血运重建的复合终点。该试验的设计和统计学效能旨在证明替罗非班与阿昔单抗相比的非劣效性。
替罗非班组的2398例患者中主要终点的发生频率高于阿昔单抗组的2411例患者（7.6%对6.0%；风险比，1.26；单侧95%置信区间上限为1.51，表明缺乏等效性，双侧95%置信区间为1.01至1.57，表明阿昔单抗优于替罗非班；P = 0.038）。复合终点各组成部分的效应大小和方向相似（死亡风险比，1.21；心肌梗死风险比，1.27；紧急靶血管血运重建风险比，1.26），替罗非班组和阿昔单抗组之间心肌梗死发生率的差异具有统计学意义（分别为6.9%和5.4%；P = 0.04）。无论年龄、性别、是否患有糖尿病或是否接受氯吡格雷预处理，阿昔单抗的相对获益都是一致的。主要出血并发症或输血发生率无显著差异，但替罗非班与较低的轻微出血事件和血小板减少发生率相关。
尽管该试验旨在评估替罗非班与阿昔单抗相比的非劣效性，但研究结果表明，与阿昔单抗相比，替罗非班对主要缺血事件的保护作用较小。
