Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA.
Am Heart J. 2009 Dec;158(6):998-1004.e1. doi: 10.1016/j.ahj.2009.10.010.
Inhibition of the P2Y12 ADP-receptor with oral antiplatelet agents given to patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is associated with improved outcomes, but this strategy is limited by the time required for maximal antiplatelet effect after administration. We examined the safety and tolerability of a novel, direct-acting, reversible, intravenous P2Y12 ADP-receptor antagonist, elinogrel, versus placebo when administered to STEMI patients before primary PCI.
The ERASE MI trial was a pilot, phase IIA, randomized, double-blind, placebo-controlled, dose-escalation study designed to evaluate the safety and tolerability of escalating doses (10, 20, 40, and 60 mg) of elinogrel administered as a single intravenous bolus before the start of the diagnostic angiogram preceding primary PCI. Patients were randomly assigned in a 1:1 manner to either elinogrel or placebo within each dosing group; and all patients received a 600-mg clopidogrel loading dose, followed by a second 300-mg clopidogrel loading dose 4 hours after PCI. The major outcome, in-hospital bleeding, was assessed with the Thrombolysis in Myocardial Infarction and Global Strategies to Open Occluded Coronary Arteries bleeding scales. Pre-PCI corrected Thrombolysis in Myocardial Infarction frame count and ST-segment resolution were also evaluated.
Seventy patients were randomized in the dose-escalation study, but the dose-confirmation phase was not started because the trial was prematurely terminated for administrative reasons. The incidence of bleeding events was infrequent and appeared to be similar in patients treated with all doses of elinogrel versus placebo. No differences in serious adverse events, laboratory values, corrected Thrombolysis in Myocardial Infarction frame count, or ST resolution were demonstrated between elinogrel and placebo.
With the limitations of a small study sample size, this pilot study provided preliminary data on the feasibility and tolerability of escalating doses of a direct-acting, reversible, intravenous P2Y12 ADP-receptor antagonist, elinogrel, as an adjunctive therapy for primary PCI for STEMI.
在接受经皮冠状动脉介入治疗（PCI）的 ST 段抬高型心肌梗死（STEMI）患者中，使用口服抗血小板药物抑制 P2Y12 二磷酸腺苷受体可改善预后，但该策略受到药物发挥最大抗血小板作用所需时间的限制。我们研究了新型直接作用、可逆、静脉内 P2Y12 二磷酸腺苷受体拮抗剂依诺格雷在 STEMI 患者行直接 PCI 前给药的安全性和耐受性。
ERASE MI 试验是一项前瞻性、ⅡA 期、随机、双盲、安慰剂对照、剂量递增研究，旨在评估依诺格雷递增剂量（10、20、40 和 60mg）作为诊断性血管造影前单次静脉推注给药的安全性和耐受性，该诊断性血管造影是直接 PCI 前的检查。患者按 1:1 随机分配至依诺格雷或安慰剂各剂量组内；所有患者均接受 600mg 氯吡格雷负荷剂量，PCI 后 4 小时再给予第二次 300mg 氯吡格雷负荷剂量。主要终点为院内出血，采用血栓溶解心肌梗死和全球开放闭塞冠状动脉策略出血量表评估。还评估了 PCI 前校正的血栓溶解心肌梗死帧数和 ST 段分辨率。
70 例患者被纳入剂量递增研究，但由于行政原因试验提前终止，故未开始剂量确认阶段。出血事件发生率较低，且依诺格雷各剂量组与安慰剂组之间似乎相似。依诺格雷与安慰剂组之间在严重不良事件、实验室值、校正的血栓溶解心肌梗死帧数或 ST 分辨率方面无差异。
受研究样本量小的限制，这项初步研究提供了关于直接作用、可逆、静脉内 P2Y12 二磷酸腺苷受体拮抗剂依诺格雷递增剂量作为 STEMI 直接 PCI 辅助治疗的可行性和耐受性的初步数据。
