Rubboli Andrea
Cardiac Catheterization Laboratory, Division of Cardiology, Maggiore Hospital, Bologna, Italy.
Curr Cardiol Rev. 2008 Feb;4(1):63-71. doi: 10.2174/157340308783565438.
A 48-hour course of intravenous unfractionated heparin (UFH) is the standard of treatment in conjunction with fibrin-specific thrombolysis in ST-elevation myocardial infarction (STEMI). In recent trials, the efficacy and safety of in-hospital administration of subcutaneous low-molecular-weight heparins (LMWH), previously proven effective in non-ST-elevation acute coronary syndromes, have been investigated in the setting of STEMI. The aim of this review was to evaluate the available evidence supporting the use of LMWH in STEMI.Overall, about 27,000 patients treated with various thrombolytic regimens, were included in 12 open-label randomized clinical trials, where dalteparin, reviparin or enoxaparin were administered. While acknowledging the wide variability in study dimensions, designs and end-points, a higher efficacy of LMWH was observed overall as compared to placebo, and also to UFH (mainly as regards the occurrence of reinfarction). As regards safety, bleedings were more frequent than placebo and comparable to UFH in LMWH groups, with the exception of the pre-hospital ASSENT-3 PLUS trial, where in elderly patients, enoxaparin had an incidence of intracranial hemorrhage twice higher than UFH. In a recent double-blind, randomized, mega-trial including over 20,000 patients, the superior efficacy on in-hospital and 30-day adverse cardiac events (namely reinfarction), and comparable safety on intracranial bleedings, of enoxaparin compared to UFH, was shown.In conclusion, in-hospital subcutaneous administration of dalteparin, reviparin and enoxaparin, as an adjunct to various thrombolytics in STEMI, appears feasible and at least as effective and safe as 48-hour intravenous treatment with UFH. In accordance with the available strongest evidence, an initial intravenous bolus of enoxaparin followed by twice daily subcutaneous administration for about 1 week should be the preferred regimen, and should be strongly considered instead of intravenous UFH. Along with its easiness of use, not requiring laboratory monitoring, subcutaneous administration of LMWH following STEMI treated with thrombolysis allows extended antithrombotic treatment, while permitting early mobilization (and rehabilitation) of patients.
在ST段抬高型心肌梗死(STEMI)中,静脉注射普通肝素(UFH)48小时是与纤维蛋白特异性溶栓联合使用的标准治疗方法。在最近的试验中,已经在STEMI的背景下研究了皮下注射低分子量肝素(LMWH)在医院内给药的疗效和安全性,LMWH先前已被证明在非ST段抬高型急性冠状动脉综合征中有效。本综述的目的是评估支持在STEMI中使用LMWH的现有证据。总体而言,12项开放标签随机临床试验纳入了约27000例接受各种溶栓方案治疗的患者,这些试验中使用了达肝素、瑞肝素或依诺肝素。尽管承认研究规模、设计和终点存在很大差异,但总体上观察到LMWH的疗效高于安慰剂,也高于UFH(主要在再梗死发生率方面)。在安全性方面,LMWH组的出血比安慰剂更频繁,与UFH相当,但院前ASSENT-3 PLUS试验除外,在该试验中,老年患者中依诺肝素的颅内出血发生率比UFH高两倍。在一项最近的包括超过20000例患者的双盲、随机、大型试验中,显示依诺肝素与UFH相比,对院内和30天不良心脏事件(即再梗死)具有更高的疗效,对颅内出血具有相当的安全性。总之,在STEMI中,皮下注射达肝素、瑞肝素和依诺肝素作为各种溶栓药物的辅助治疗似乎是可行的,并且至少与静脉注射UFH 48小时治疗一样有效和安全。根据现有最有力的证据,初始静脉推注依诺肝素,然后每日两次皮下给药约1周应是首选方案,并且应强烈考虑替代静脉注射UFH。除了使用方便,无需实验室监测外,STEMI溶栓治疗后皮下注射LMWH还允许延长抗血栓治疗,同时允许患者早期活动(和康复)。