Tcheng J E, Harrington R A, Kottke-Marchant K, Kleiman N S, Ellis S G, Kereiakes D J, Mick M J, Navetta F I, Smith J E, Worley S J
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Circulation. 1995 Apr 15;91(8):2151-7. doi: 10.1161/01.cir.91.8.2151.
Platelet aggregation and thrombosis have been implicated in the pathogenesis of coronary angioplasty complications. Integrelin, a synthetic cyclic heptapeptide with high affinity and marked specificity for platelet integrin glycoprotein IIb/IIIa, effectively blocks ADP-induced platelet aggregation.
In 150 patients undergoing elective percutaneous coronary intervention, random assignment was made to one of three treatment regimens: placebo; a 90-micrograms/kg bolus of Integrelin before angioplasty followed by a 1.0-micrograms.kg-1.min-1 infusion of Integrelin for 4 hours; or a 90-micrograms/kg bolus followed by a 1.0-microgram.kg-1.min-1 infusion of Integrelin for 12 hours. Patients were followed to 30 days for the composite occurrence of myocardial infarction, stent implantation, repeat urgent or emergency percutaneous intervention or coronary bypass surgery, or death. Pharmacodynamic data were obtained in a subset of 31 patients. Administration of a 90-micrograms/kg bolus of Integrelin achieved an 86% inhibition of platelet aggregation, and this inhibition was maintained by a 1.0-microgram.kg-1.min-1 infusion. There was a trend toward reduction in end-point events from 12.2% (placebo) to 9.6% (4-hour infusion) to 4.1% (12-hour infusion), although these differences were not statistically significant (P = .13 for the 12-hour group compared with placebo). Major bleeding occurred in 8%, 8%, and 2% of patients, while minor bleeding was observed in 14%, 33%, and 47% of patients, respectively. There was no difference in bleeding index among groups (1.5, 1.7, and 1.3, respectively), defined as [(change in hematocrit/3)+red blood cell units transfused].
This first clinical investigation of Integrelin during routine, elective, low- and high-risk coronary intervention supports the potential efficacy of Integrelin in routine coronary interventions. Pharmacodynamic analyses demonstrate that profound and sustained inhibition of platelet function is achieved, although a higher bolus dose may be required. Definitive assessment of efficacy and safety will need to await a large-scale study powered to achieve statistical significance.
血小板聚集和血栓形成与冠状动脉血管成形术并发症的发病机制有关。依替巴肽是一种对血小板整合素糖蛋白IIb/IIIa具有高亲和力和显著特异性的合成环七肽，可有效阻断ADP诱导的血小板聚集。
在150例接受择期经皮冠状动脉介入治疗的患者中，随机分配至三种治疗方案之一：安慰剂；血管成形术前静脉推注90微克/千克依替巴肽，随后以1.0微克·千克-1·分钟-1的速度输注依替巴肽4小时；或静脉推注90微克/千克依替巴肽，随后以1.0微克·千克-1·分钟-1的速度输注依替巴肽12小时。对患者进行30天随访，观察心肌梗死、支架植入、重复紧急或急诊经皮介入治疗或冠状动脉搭桥手术或死亡的复合事件发生情况。在31例患者的亚组中获取了药效学数据。静脉推注90微克/千克依替巴肽可使血小板聚集抑制率达到86%，并通过以1.0微克·千克-1·分钟-1的速度输注来维持这种抑制作用。终点事件有从12.2%（安慰剂组）降至9.6%（4小时输注组）再降至4.1%（12小时输注组）的趋势，尽管这些差异无统计学意义（12小时输注组与安慰剂组相比，P = 0.13）。主要出血分别发生在8%、8%和2%的患者中，而轻微出血分别见于14%、33%和47%的患者。各组间出血指数无差异（分别为1.5、1.7和1.3），出血指数定义为[（血细胞比容变化/3）+输注的红细胞单位数]。
这项关于依替巴肽在常规、择期、低风险和高风险冠状动脉介入治疗期间的首次临床研究支持了依替巴肽在常规冠状动脉介入治疗中的潜在疗效。药效学分析表明，尽管可能需要更高的推注剂量，但可实现对血小板功能的深度和持续抑制。对疗效和安全性的明确评估有待进行一项有足够统计学效力的大规模研究。
