Tardiff B E, Jennings L K, Harrington R A, Gretler D, Potthoff R F, Vorchheimer D A, Eisenberg P R, Lincoff A M, Labinaz M, Joseph D M, McDougal M F, Kleiman N S
Duke Clinical Research Institute, Durham, NC, USA.
Circulation. 2001 Jul 24;104(4):399-405. doi: 10.1161/hc2901.093500.
Platelet deposition and aggregation are central to the pathogenesis of ischemic complications of acute coronary syndromes (ACS). Pharmacodynamic effects of the platelet glycoprotein IIb/IIIa antagonist eptifibatide have been delineated in healthy subjects but not in patients with ACS. We assessed effects of eptifibatide on ex vivo platelet aggregation in patients enrolled in the Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy (PURSUIT) trial of ACS.
Patients were randomly assigned to an intravenous bolus (180 microgram/kg) and 72-hour infusion of eptifibatide (2.0 microgram/kg per minute, n=48) or placebo (n=50). We assessed correlations of plasma eptifibatide levels with receptor occupancy and inhibition of ex vivo platelet aggregation at 5 minutes and 1, 4, 24, 48, and 72 hours during treatment and 4 and 8 hours after termination of infusion. Blood was collected in buffered citrate and D-phenylalanyl-L-prolyl-L-arginine chloromethylketone anticoagulants. Although eptifibatide produced profound, prolonged inhibition of platelet aggregation during therapy, aggregation appeared to recover partially by 4 hours after the bolus. The aggregation response was greater with thrombin receptor agonist peptide versus ADP stimulation; inhibition of platelet aggregation was greater in blood samples anticoagulated with citrate versus D-phenylalanyl-L-prolyl-L-arginine chloromethylketone (PPACK). Plasma eptifibatide levels correlated significantly with receptor occupancy but not with inhibition of platelet aggregation.
A bolus and infusion of eptifibatide inhibits platelet aggregation profoundly in patients with ACS and is followed by brief, partial recovery. These results enhance our understanding of the relation between pharmacodynamic and clinical effects of eptifibatide in such patients and may have important implications for its use in percutaneous interventions.
血小板沉积和聚集是急性冠状动脉综合征（ACS）缺血性并发症发病机制的核心。血小板糖蛋白IIb/IIIa拮抗剂依替巴肽的药效学作用已在健康受试者中得到描述，但在ACS患者中尚未明确。我们在不稳定型心绞痛中血小板糖蛋白IIb/IIIa：使用依替巴肽（Integrilin）进行受体抑制治疗（PURSUIT）试验的ACS患者中，评估了依替巴肽对体外血小板聚集的影响。
患者被随机分配接受静脉推注（180微克/千克）和72小时输注依替巴肽（2.0微克/千克每分钟，n = 48）或安慰剂（n = 50）。我们评估了治疗期间5分钟、1、4、24、48和72小时以及输注终止后4和8小时血浆依替巴肽水平与受体占有率以及体外血小板聚集抑制之间的相关性。血液采集于枸橼酸盐缓冲液和D-苯丙氨酰-L-脯氨酰-L-精氨酸氯甲基酮抗凝剂中。尽管依替巴肽在治疗期间对血小板聚集产生了深刻、持久的抑制作用，但推注后4小时聚集似乎部分恢复。与ADP刺激相比，凝血酶受体激动肽刺激后的聚集反应更大；与D-苯丙氨酰-L-脯氨酰-L-精氨酸氯甲基酮（PPACK）抗凝的血样相比，枸橼酸盐抗凝的血样中血小板聚集的抑制作用更强。血浆依替巴肽水平与受体占有率显著相关，但与血小板聚集抑制无关。
推注和输注依替巴肽可在ACS患者中显著抑制血小板聚集，随后有短暂的部分恢复。这些结果加深了我们对依替巴肽在此类患者中药效学和临床效果之间关系的理解，可能对其在经皮介入治疗中的应用具有重要意义。
