Théroux P, Kouz S, Roy L, Knudtson M L, Diodati J G, Marquis J F, Nasmith J, Fung A Y, Boudreault J R, Delage F, Dupuis R, Kells C, Bokslag M, Steiner B, Rapold H J
Department of Medicine, Montreal Heart Institute, Quebec, Canada.
Circulation. 1996 Sep 1;94(5):899-905. doi: 10.1161/01.cir.94.5.899.
Ligand binding to the platelet membrane receptor glycoprotein (GP) IIb/IIIa, the final and obligatory step to platelet aggregation, can now be inhibited by pharmacological agents. This study was designed to evaluate the potential of lamifiban, a novel nonpeptide antagonist of GP IIb/IIIa, for the management of unstable angina.
In a prospective, dose-ranging, double-blind study, 365 patients with unstable angina were randomized to an infusion of 1, 2, 4, or 5 micrograms/min of lamifiban or of placebo. Treatment was administered for 72 to 120 hours. Outcome events were measured during the infusion period and after 1 month. Concomitant aspirin was administered to all patients and heparin to 28% of patients. Lamifiban, all doses combined, reduced the risk of death, nonfatal myocardial infarction, or the need for an urgent revascularization during the infusion period from 8.1% to 3.3% (P = .04). The rates were 2.5%, 4.9%, 3.3%, and 2.4% with increasing doses. At 1 month, death or nonfatal infarction occurred in 8.1% of patients with placebo and in 2.5% of patients with the two high doses (P = .03). The highest dose of lamifiban additionally prevented the need for an urgent intervention. Lamifiban dose-dependently inhibited platelet aggregation. Bleeding times were significantly prolonged with platelet inhibition of > 80%. Major (but neither life-threatening nor intracranial) bleedings occurred in 0.8% of patients with placebo and 2.9% with lamifiban.
The nonpeptide GP IIb/IIIa antagonist lamifiban protected patients with unstable angina from severe ischemic events during a 3- to 5-day infusion and reduced the incidence of death and infarction at 1 month, suggesting considerable promise for this new therapeutic approach.
配体与血小板膜受体糖蛋白（GP）IIb/IIIa结合是血小板聚集的最终且必要步骤，目前可被药物制剂抑制。本研究旨在评估新型非肽类GP IIb/IIIa拮抗剂拉米非班治疗不稳定型心绞痛的潜力。
在一项前瞻性、剂量范围、双盲研究中，365例不稳定型心绞痛患者被随机分为接受1、2、4或5微克/分钟的拉米非班输注或安慰剂输注。治疗持续72至120小时。在输注期间和1个月后测量结局事件。所有患者均服用阿司匹林，28%的患者服用肝素。所有剂量的拉米非班联合使用可将输注期间死亡、非致命性心肌梗死或紧急血运重建的风险从8.1%降至3.3%（P = 0.04）。随着剂量增加，发生率分别为2.5%、4.9%、3.3%和2.4%。在1个月时，安慰剂组8.1%的患者发生死亡或非致命性梗死，两个高剂量组为2.5%（P = 0.03）。拉米非班的最高剂量还避免了紧急干预的需要。拉米非班剂量依赖性地抑制血小板聚集。血小板抑制率>80%时出血时间显著延长。安慰剂组0.8%的患者和拉米非班组2.9%的患者发生了严重（但非危及生命或颅内）出血。
非肽类GP IIb/IIIa拮抗剂拉米非班在3至5天的输注期间可保护不稳定型心绞痛患者免受严重缺血事件影响，并降低1个月时的死亡和梗死发生率，表明这种新的治疗方法颇具前景。
