Cannon C P, McCabe C H, Wilcox R G, Langer A, Caspi A, Berink P, Lopez-Sendon J, Toman J, Charlesworth A, Anders R J, Alexander J C, Skene A, Braunwald E
Brigham and Women's Hospital, Boston, MA 02115, USA.
Circulation. 2000 Jul 11;102(2):149-56. doi: 10.1161/01.cir.102.2.149.
Although intravenous glycoprotein IIb/IIIa inhibitors are beneficial in patients with acute coronary syndromes, prolonged oral IIb/IIIa inhibition might provide an additional reduction in recurrent events.
Investigators at 888 hospitals in 29 countries enrolled 10 288 patients with acute coronary syndromes, which was defined as ischemic pain at rest within 72 hours of randomization, associated with positive cardiac markers, electrocardiographic changes, or prior cardiovascular disease. Patients received aspirin and were randomized to receive, for the duration of the trial, (1) 50 mg of orbofiban twice daily (50/50 group), (2) 50 mg of orbofiban twice daily for 30 days followed by 30 mg of orbofiban twice daily (50/30 group), or (3) a placebo. The primary composite end point was death, myocardial infarction, recurrent ischemia requiring rehospitalization, urgent revascularization, or stroke. The trial was terminated prematurely because of an unexpected increase in 30-day mortality in the 50/30 orbofiban group. Mortality through 10 months was 3.7% for the placebo group versus 5.1% in the 50/30 group (P=0.008) and 4.5% in the 50/50 group (P=0.11). There were no differences in the primary end point (22.9%, 23.1%, and 22.8%, for the placebo, 50/30, and 50/50 groups, respectively). Major or severe bleeding (but not intracranial hemorrhage) was higher with orbofiban; it occurred in 2. 0%, 3.7% (P=0.0004), and 4.5% (P<0.0001) of patients, respectively. Exploratory subgroup analyses found that patients who underwent percutaneous coronary intervention had a lower mortality and a significant reduction in the composite end point (P=0.001) with orbofiban.
-Fixed-dose orbofiban failed to reduce major cardiovascular events and was associated with increased mortality in this broad population of patients with acute coronary syndromes; however, a benefit was observed among patients who underwent percutaneous coronary intervention.
尽管静脉注射糖蛋白IIb/IIIa抑制剂对急性冠脉综合征患者有益，但长期口服IIb/IIIa抑制剂可能会进一步降低复发事件。
来自29个国家888家医院的研究人员纳入了10288例急性冠脉综合征患者，该综合征定义为随机分组后72小时内的静息性缺血性疼痛，伴有心脏标志物阳性、心电图改变或既往心血管疾病。患者接受阿司匹林治疗，并在试验期间随机分为三组：（1）每日两次口服50毫克奥波非班（50/50组）；（2）前30天每日两次口服50毫克奥波非班，之后每日两次口服30毫克奥波非班（50/30组）；（3）安慰剂组。主要复合终点为死亡、心肌梗死、因复发缺血需再次住院、紧急血运重建或中风。由于50/30奥波非班组30天死亡率意外增加，试验提前终止。安慰剂组10个月时的死亡率为3.7%，50/30组为5.1%（P = 0.008），50/50组为4.5%（P = 0.11）。主要终点无差异（安慰剂组、50/30组和50/50组分别为22.9%、23.1%和22.8%）。奥波非班组的主要或严重出血（但不包括颅内出血）发生率更高；分别有2.0%、3.7%（P = 0.0004）和4.5%（P < 0.0001）的患者发生出血。探索性亚组分析发现，接受经皮冠状动脉介入治疗的患者使用奥波非班后死亡率较低，复合终点显著降低（P = 0.001）。
在这一广泛的急性冠脉综合征患者群体中，固定剂量的奥波非班未能降低主要心血管事件，且与死亡率增加相关；然而，在接受经皮冠状动脉介入治疗的患者中观察到了益处。
