Ibbotson Tim, McGavin Jane K, Goa Karen L
Adis International Inc., Yardley, Pennsylvania 19067, USA.
Am J Cardiovasc Drugs. 2003;3(5):381-6. doi: 10.2165/00129784-200303050-00011.
Abciximab (Reopro) is an antibody fragment that dose-dependently inhibits platelet aggregation and leucocyte adhesion by binding to the glycoprotein (GP) IIb/IIIa, vitronectin and Mac-1 receptors. Abciximab (0.25 mg/kg bolus plus infusion of 0.125 micro g/kg/min for 12 hours) showed greater efficacy than tirofiban in reducing the 30-day composite endpoint of death, nonfatal myocardial infarction (MI) or urgent target-vessel revascularization in the randomized, double-blind TARGET study in patients scheduled for stent placement. In addition, the beneficial effects of treatment with abciximab previously observed in the randomized, multicenter, placebo-controlled EPILOG and EPISTENT studies have been maintained to 1 year, with a significantly reduced incidence of ischemic complications relative to placebo consistently observed across a range of subgroups including age, sex, bodyweight and indication for revascularization. The incidence of the composite endpoint was reduced in patients presenting with acute MI of <48 hours' duration in comparison with either fibrinolytic therapy or stenting alone in the randomized STOPAMI and ADMIRAL trials, primarily because of a reduced requirement for urgent repeat revascularization and reduced incidence of mortality. In the randomized, nonblind, multicenter CADILLAC trial in patients with acute myocardial infarction (MI), stenting alone was superior to percutaneous transluminal coronary angioplasty (PTCA) and stenting alone was not inferior to PTCA plus abciximab. Recent large randomized, multicenter studies (ASSENT-3 and GUSTO-V) have shown higher efficacy (on various ischemic endpoints) of abciximab in combination with either a reduced dose of tenecteplase or reteplase compared with the fibrinolytic drug alone. TIMI grade 3 flow rates at 60 and 90 minutes in the TIMI-14 and SPEED trials were higher in patients who received abciximab in combination with either alteplase or reteplase than abciximab alone and were similar to that seen with the full-dose fibrinolytic alone. In the randomized, multicenter GUSTO IV-ACS study, no significant differences in any of the ischemic endpoints at either 7 or 30 days in patients with acute coronary syndromes who were not scheduled to undergo early revascularization (within 12 hours of end of infusion) were apparent between those who received abciximab (bolus and either 24- or 48-hour infusion) and those who received placebo in addition to aspirin and heparin. The most common adverse events associated with the use of abciximab are bleeding complications and thrombocytopenia, although the risk of major bleeding can be limited through adhering to current administration protocols. Treatment costs are generally higher in both stent plus abciximab and angioplasty plus abciximab groups than stent plus placebo, primarily because of the acquisition cost of abciximab. Abciximab appeared most cost beneficial in high-risk patients undergoing elective percutaneous coronary revascularization; among lower risk patients, abciximab therapy has been associated with higher total in-hospital and 6-month medical costs than eptifibatide.
The GP IIb/IIIa receptor antagonist abciximab, when used with aspirin and heparin, has demonstrated efficacy in reducing the short- and long-term risk of ischemic complications in patients with ischemic heart disease undergoing percutaneous coronary intervention, when used with aspirin and heparin. High-risk patients (including those with diabetes mellitus) derive particular benefits from abciximab treatment. Abciximab remains an important therapeutic option for the prevention of complications in patients with ischaemic heart disease.
阿昔单抗(Reopro)是一种抗体片段,通过与糖蛋白(GP)IIb/IIIa、玻连蛋白和Mac-1受体结合,剂量依赖性地抑制血小板聚集和白细胞黏附。在针对计划进行支架置入的患者开展的随机、双盲TARGET研究中,阿昔单抗(0.25 mg/kg静脉推注加0.125 μg/kg/min输注12小时)在降低30天死亡、非致死性心肌梗死(MI)或紧急靶血管血运重建的复合终点方面显示出比替罗非班更高的疗效。此外,先前在随机、多中心、安慰剂对照的EPILOG和EPISTENT研究中观察到的阿昔单抗治疗的有益效果已维持至1年,在包括年龄、性别、体重和血运重建指征在内的一系列亚组中,相对于安慰剂,缺血并发症的发生率持续显著降低。在随机、非盲、多中心CADILLAC试验中,对于急性心肌梗死(MI)患者,单纯支架置入优于经皮腔内冠状动脉成形术(PTCA),且单纯支架置入不劣于PTCA加阿昔单抗。近期大型随机、多中心研究(ASSENT-3和GUSTO-V)表明,与单独使用纤溶药物相比,阿昔单抗联合降低剂量的替奈普酶或瑞替普酶在各种缺血终点方面具有更高的疗效。在TIMI-14和SPEED试验中,接受阿昔单抗联合阿替普酶或瑞替普酶治疗的患者在60分钟和90分钟时的TIMI 3级血流率高于单独使用阿昔单抗的患者,且与单独使用全剂量纤溶药物时相似。在随机、多中心GUSTO IV-ACS研究中,对于未计划进行早期血运重建(输注结束后12小时内)的急性冠状动脉综合征患者,在7天或30天时的任何缺血终点方面,接受阿昔单抗(静脉推注及24小时或48小时输注)的患者与接受阿司匹林和肝素加安慰剂的患者之间均未显示出显著差异。与使用阿昔单抗相关的最常见不良事件是出血并发症和血小板减少症,尽管通过遵循当前给药方案可将大出血风险限制在一定范围内。支架加阿昔单抗组和血管成形术加阿昔单抗组的治疗成本通常均高于支架加安慰剂组,主要原因是阿昔单抗的购置成本。阿昔单抗在接受择期经皮冠状动脉血运重建的高危患者中似乎最具成本效益;在低风险患者中,与依替巴肽相比,阿昔单抗治疗与更高的住院总费用和6个月医疗费用相关。
GP IIb/IIIa受体拮抗剂阿昔单抗与阿司匹林和肝素联合使用时,已证明在接受经皮冠状动脉介入治疗的缺血性心脏病患者中,可有效降低短期和长期缺血并发症风险。高危患者(包括糖尿病患者)从阿昔单抗治疗中获益尤为显著。阿昔单抗仍然是预防缺血性心脏病患者并发症的重要治疗选择。