依替巴肽与小剂量替奈普酶联合再灌注治疗ST段抬高型心肌梗死：急性心肌梗死中依替巴肽与替奈普酶（INTEGRITI）II期血管造影试验结果

Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction: results of the integrilin and tenecteplase in acute myocardial infarction (INTEGRITI) Phase II Angiographic Trial.

作者信息

Giugliano Robert P, Roe Matthew T, Harrington Robert A, Gibson C Michael, Zeymer Uwe, Van de Werf Frans, Baran Kenneth W, Hobbach Hans Peter, Woodlief Lynn H, Hannan Karen L, Greenberg Sally, Miller Joanne, Kitt Michael M, Strony John, McCabe Carolyn H, Braunwald Eugene, Califf Robert M

机构信息

TIMI Study Group, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

出版信息

J Am Coll Cardiol. 2003 Apr 16;41(8):1251-60. doi: 10.1016/s0735-1097(03)00123-2.

DOI:10.1016/s0735-1097(03)00123-2

PMID:12706917

Abstract

OBJECTIVES

The goal of this study was to evaluate combinations of eptifibatide with reduced-dose tenecteplase (TNK) in ST-elevation myocardial infarction (STEMI).

BACKGROUND

Glycoprotein IIb/IIIa inhibitors enhance thrombolysis. The role of combination therapy in clinical practice remains to be established.

METHODS

Patients (n = 438) with STEMI <6 h were enrolled. In dose-finding, 189 patients were randomized to different combinations of double-bolus eptifibatide and reduced-dose TNK. In dose-confirmation, 249 patients were randomized 1:1 to eptifibatide 180 microg/kg bolus, 2 microg/kg/min infusion, and 180 microg/kg bolus 10 min later (180/2/180) plus half-dose TNK (0.27 mg/kg) or standard-dose (0.53 mg/kg) TNK monotherapy. All patients received aspirin and unfractionated heparin (60 U/kg bolus; infusion 7 U/kg/h [combination], 12 U/kg/h [monotherapy]). The primary end point was Thrombolysis In Myocardial Infarction (TIMI) grade 3 epicardial flow at 60 min.

RESULTS

In dose-finding, TIMI grade 3 flow rates were similar across groups (64% to 68%). Arterial patency was highest for eptifibatide 180/2/180 plus half-dose TNK (96%, p = 0.02 vs. eptifibatide 180/2/90 plus half-dose TNK). In dose-confirmation, this combination, compared with TNK monotherapy, tended to achieve more TIMI 3 flow (59% vs. 49%, p = 0.15), arterial patency (85% vs. 77%, p = 0.17), and ST-segment resolution (median 71% vs. 61%, p = 0.08) but was associated with more major hemorrhage (7.6% vs. 2.5%, p = 0.14) and transfusions (13.4% vs. 4.2%, p = 0.02). Intracranial hemorrhage occurred in 1.0%, 0.6%, and 1.7% of patients treated with any combination, eptifibatide 180/2/180 and half-dose TNK, and TNK monotherapy, respectively.

CONCLUSIONS

Double-bolus eptifibatide (180/2/180) plus half-dose TNK tended to improve angiographic flow and ST-segment resolution compared with TNK monotherapy but was associated with more transfusions and non-cerebral bleeding. Further study is needed before this combination can be recommended for general use.

摘要

目的

本研究旨在评估依替巴肽与小剂量替奈普酶（TNK）联合应用于ST段抬高型心肌梗死（STEMI）的效果。

背景

糖蛋白IIb/IIIa抑制剂可增强溶栓效果。联合治疗在临床实践中的作用仍有待确定。

方法

纳入发病时间<6小时的STEMI患者438例。在剂量探索阶段，189例患者随机接受双剂量依替巴肽与小剂量TNK的不同联合方案。在剂量确认阶段，249例患者按1:1随机分组，分别接受依替巴肽180μg/kg静脉推注、2μg/kg/min静脉滴注、10分钟后再推注180μg/kg（180/2/180）加半量TNK（0.27mg/kg）或标准剂量（0.53mg/kg）TNK单药治疗。所有患者均接受阿司匹林和普通肝素治疗（静脉推注60U/kg；联合治疗组静脉滴注7U/kg/h，单药治疗组静脉滴注12U/kg/h）。主要终点为60分钟时心肌梗死溶栓（TIMI）3级心外膜血流。

结果

在剂量探索阶段，各组TIMI 3级血流率相似（64%至68%）。依替巴肽180/2/180加半量TNK组的动脉通畅率最高（96%，与依替巴肽180/2/90加半量TNK组相比，p = 0.02）。在剂量确认阶段，与TNK单药治疗相比，该联合方案倾向于获得更多TIMI 3级血流（59%对49%，p = 0.15）、更高的动脉通畅率（85%对77%，p = 0.17）和更高的ST段回落幅度（中位数71%对61%，p = 0.08），但与更多的严重出血（7.6%对2.5%，p = 0.14）和输血（13.4%对4.2%，p = 0.02）相关。接受任何联合方案、依替巴肽180/2/180加半量TNK以及TNK单药治疗的患者颅内出血发生率分别为1.0%、0.6%和1.7%。