Romagnoli Enrico, Burzotta Francesco, Trani Carlo, Biondi-Zoccai Giuseppe G L, Giannico Floriana, Crea Filippo
Department of cardiovascular disease, Catholic University, Campobasso, Italy.
J Thromb Thrombolysis. 2007 Feb;23(1):57-63. doi: 10.1007/s11239-006-9000-0.
The present review aims to describe the pharmacological aspects as well as the available clinical data supporting the choice of intracoronary route of administration for abciximab, an antiplatelet drug used in patients with acute coronary syndromes undergoing percutaneous coronary interventions (PCI). Abciximab is a glycoprotein (GP) IIb/IIIa receptor antagonist which determines a potent inhibition of platelet aggregation and thrombus formation. These properties seem to prevent not only thrombus formation but also to promote (at higher drug concentration) lysis of fresh thrombus. Moreover, differently from the other GP IIb/IIIa inhibitors, abciximab also binds to the vitronectin receptor on endothelial, smooth muscle, and inflammatory cells and to an activated conformation of the aMb2 receptor on leukocytes. Such cross-reactivity raises the possibility that clinical benefits derived from its use may not be exclusively due to its anti-thrombotic effect, but may also be related to the suppression of inflammatory pathways involving platelets, white blood cells, and the vascular endothelium. On such basis, the local administration of abciximab at the site of coronary thrombosis may enhance, by increasing its local concentration, the binding to both platelet and endothelium receptors. The results of several angiographic studies assessing the effect of intracoronary abciximab administration support on clinical grounds its adoption in patients with fresh coronary thrombosis. Indeed, better post-angioplasty coronary flow, greater degree of myocardial salvage and a better left ventricular function recovery have been achieved as compared to the intravenous, systemic, administration of drug's bolus. Condensed Abstract Several studies have highlighted the benefits of abciximab, a potent antiplatelet agent, in patients with acute coronary syndromes undergoing percutaneous coronary interventions. Moreover, differently from the other glycoprotein IIb/IIIa receptor antagonists, abciximab also has non-IIb/IIIa-related properties raising the possibility that clinical benefits derived from its use may not be exclusively due to its anti-thrombotic effect, but may also be related to the suppression of inflammatory pathways. Several angiographic studies in patients with fresh coronary thrombosis and recent clinical studies in patients with acute coronary syndromes undergoing mechanical revascularization support the hypothesis that local administration of abciximab at the site of the culprit coronary artery may facilitate both the de-thrombotic and the non-GP IIb/IIIa-dependent properties of the drug. On such basis, the present review aims to describe the pharmacological aspects as well as the available clinical data supporting the choice of intracoronary route of administration for abciximab.
本综述旨在描述阿昔单抗(一种用于接受经皮冠状动脉介入治疗(PCI)的急性冠状动脉综合征患者的抗血小板药物)冠状动脉内给药途径选择的药理学方面以及现有临床数据。阿昔单抗是一种糖蛋白(GP)IIb/IIIa受体拮抗剂,可有效抑制血小板聚集和血栓形成。这些特性似乎不仅能防止血栓形成,还能(在较高药物浓度下)促进新鲜血栓的溶解。此外,与其他GP IIb/IIIa抑制剂不同,阿昔单抗还与内皮细胞、平滑肌细胞和炎症细胞上的玻连蛋白受体以及白细胞上活化构象的aMb2受体结合。这种交叉反应性增加了其临床益处可能并非仅因其抗血栓作用,还可能与抑制涉及血小板、白细胞和血管内皮的炎症途径有关的可能性。基于此,在冠状动脉血栓形成部位局部应用阿昔单抗可能通过增加其局部浓度来增强其与血小板和内皮受体的结合。多项评估冠状动脉内应用阿昔单抗效果的血管造影研究从临床角度支持了其在新鲜冠状动脉血栓形成患者中的应用。事实上,与静脉内全身性给予药物推注相比,血管成形术后冠状动脉血流更好、心肌挽救程度更高且左心室功能恢复更好。简要摘要 多项研究强调了强效抗血小板药物阿昔单抗在接受经皮冠状动脉介入治疗的急性冠状动脉综合征患者中的益处。此外,与其他糖蛋白IIb/IIIa受体拮抗剂不同,阿昔单抗还具有与IIb/IIIa无关的特性,这增加了其临床益处可能并非仅因其抗血栓作用,还可能与抑制炎症途径有关的可能性。多项针对新鲜冠状动脉血栓形成患者的血管造影研究以及近期针对接受机械血运重建的急性冠状动脉综合征患者的临床研究支持了以下假设:在罪犯冠状动脉部位局部应用阿昔单抗可能促进该药物的溶栓和非GP IIb/IIIa依赖性特性。基于此,本综述旨在描述阿昔单抗冠状动脉内给药途径选择的药理学方面以及现有临床数据。