Tcheng J E
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
Am J Cardiol. 1996 Aug 14;78(3A):35-40. doi: 10.1016/s0002-9149(96)00490-0.
Clinical evaluation of the antiplatelet glycoprotein (GP) IIb/IIIa receptor antagonists has now extended over nearly a decade. The largest experience to date with this new class of agents has been in the prevention and management of complications of percutaneous coronary intervention. Four trials involving 3 different agents in the setting of coronary intervention are discussed: the Evaluation of c7E3 in Preventing Ischemic Complications (EPIC) and the Evaluation of PTCA to Improve Long-term Outcome by c7E3 GPIIB/IIIA Receptor Blockade (EPILOG) trials of the antibody fragment abciximab (ReoPro); the Integrilin to Minimize Platelet Aggregation and Prevent Coronary Thrombosis II (IMPACT II) trial evaluating the peptide Intergrilin; and the Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis (RESTORE) trial studying the nonpeptide mimetic tirofiban (Aggrastat). All 3 agents reduced the incidence of clinically relevant endpoint events but to differing degrees and for varying durations. The increased rates of bleeding complications seen in the EPIC trial appear to be lessened by the use of competitive GP IIb/IIIa inhibitors and by studious titration of heparin and careful groin management. The findings in IMPACT II and EPILOG suggest that the entire spectrum of patients who undergo coronary intervention benefit from GP IIb/IIIa blockade. Based on the results of these trials, platelet GP IIb/IIIa integrin blockade appears to be instrumental in improving clinical outcomes following percutaneous intervention, with clinical benefit extending to all patient categories. Bleeding risks can be minimized by minor changes in standard patient care algorithms. Dosing strategies and treatment duration still need to be refined, especially for the competitive antagonists. The role of these agents as adjuncts in stenting and rotational atherectomy and as adjunctive therapy in other disease settings requires further study.
抗血小板糖蛋白（GP）IIb/IIIa受体拮抗剂的临床评估至今已历时近十年。迄今为止，这类新型药物的最大规模应用经验来自经皮冠状动脉介入治疗并发症的预防和管理。本文讨论了三项涉及冠状动脉介入治疗中三种不同药物的试验：抗体片段阿昔单抗（ReoPro）的预防缺血性并发症的c7E3评估（EPIC）试验以及通过c7E3 GPIIB/IIIA受体阻滞改善长期结果的PTCA评估（EPILOG）试验；评估肽类药物Integrilin的Integrilin最小化血小板聚集和预防冠状动脉血栓形成II（IMPACT II）试验；以及研究非肽类模拟物替罗非班（Aggrastat）的替罗非班治疗结果和再狭窄的随机疗效研究（RESTORE）试验。所有这三种药物均降低了临床相关终点事件的发生率，但程度不同，持续时间也各异。通过使用竞争性GP IIb/IIIa抑制剂、仔细滴定肝素以及精心管理腹股沟，EPIC试验中出现的出血并发症发生率似乎有所降低。IMPACT II和EPILOG试验的结果表明，接受冠状动脉介入治疗的所有患者均能从GP IIb/IIIa受体阻滞中获益。基于这些试验结果，血小板GP IIb/IIIa整合素阻滞似乎有助于改善经皮介入治疗后的临床结局，临床获益扩展至所有患者类别。通过对标准患者护理方案进行微小调整，可将出血风险降至最低。给药策略和治疗持续时间仍需进一步优化，尤其是对于竞争性拮抗剂。这些药物在支架置入术和旋磨术作为辅助治疗以及在其他疾病背景下作为辅助治疗的作用，还需要进一步研究。
