Ibbotson Tim, Goa Karen L
Adis International Limited, Auckland, New Zealand.
Drugs. 2002;62(9):1407-30. doi: 10.2165/00003495-200262090-00017.
Enoxaparin (enoxaparin sodium) is a low molecular weight heparin (LMWH) indicated for use in the treatment of ischaemic complications of unstable angina and non-Q wave myocardial infarction (MI). Unfractionated heparin (UFH) has for many years represented the standard in anticoagulant therapy for patients with acute coronary syndromes; however, recent studies suggest that enoxaparin is also a viable option for anticoagulant therapy in these patients. The ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events) and the TIMI 11B (Thrombolysis in Myocardial Infarction) studies reported that twice daily enoxaparin was significantly more effective than a continuous infusion of UFH in reducing the composite triple endpoint of death, MI, or recurrent angina or urgent revascularisation. Follow-up of both patient populations showed continued benefit associated with enoxaparin. Enoxaparin has been compared with tinzaparin in the treatment of unstable coronary artery disease using a nonblind study design. There was no difference between treatment groups in the therapeutic endpoints. Three nonblind studies have also compared the effects of enoxaparin and UFH in patients receiving thrombolytic therapy following acute MI. The HART II (Heparin and Aspirin Reperfusion Therapy), the ASSENT 3 (Assessment of the Safety and Efficacy of a New Thrombolytic Regimen) and the ENTIRE-TIMI 23 (Enoxaparin and Tenecteplase with or without glycoprotein IIb/IIIa Inhibitor as Reperfusion strategy in ST Elevation MI - Thrombolysis in Myocardial Infarction) studies have revealed that enoxaparin in combination with alteplase or tenecteplase is at least equivalent (HART II and ENTIRE-TIMI 23), and possibly superior (ASSENT 3) to UFH. Enoxaparin is administered as a twice-daily subcutaneous injection. In contrast, UFH is administered as an intravenous infusion which requires routine monitoring of the activated partial thromboplastin time to ensure adequate levels of anticoagulation are maintained. During the acute phase of the the ESSENCE and TIMI 11B studies, the incidence of major bleeding was similar in patients receiving enoxaparin to that in patients receiving UFH. In contrast, the rates of minor bleeding were higher in patients receiving enoxaparin than in those receiving UFH throughout these studies.
Data from the ESSENCE, TIMI 11B and ASSENT 3 studies have prompted calls for those LMWHs which have been shown to be superior to UFH, to be considered as first choice treatment for anticoagulation in unstable coronary syndromes. To date, these suggestions are not reflected in current guidelines which consider UFH and LMWHs equally. Irrespective, the clinical data reported in this review support the use of enoxaparin in the treatment of acute coronary syndromes. These data suggest that enoxaparin shows certain clinical and practical advantages over standard treatment with UFH and represents an important development in the treatment of acute coronary syndromes.
依诺肝素(依诺肝素钠)是一种低分子量肝素(LMWH),适用于治疗不稳定型心绞痛和非Q波心肌梗死(MI)的缺血性并发症。普通肝素(UFH)多年来一直是急性冠状动脉综合征患者抗凝治疗的标准药物;然而,最近的研究表明,依诺肝素也是这些患者抗凝治疗的一个可行选择。ESSENCE(皮下注射依诺肝素在非Q波冠状动脉事件中的疗效和安全性)和TIMI 11B(心肌梗死溶栓)研究报告称,每日两次皮下注射依诺肝素在降低死亡、心肌梗死或复发性心绞痛或紧急血运重建的复合三联终点方面明显比持续静脉输注UFH更有效。对这两组患者的随访显示,依诺肝素持续有益。在一项非盲研究设计中,已将依诺肝素与替扎肝素用于不稳定冠状动脉疾病的治疗进行了比较。治疗组在治疗终点方面没有差异。三项非盲研究还比较了依诺肝素和UFH对急性心肌梗死后接受溶栓治疗患者的影响。HART II(肝素和阿司匹林再灌注治疗)、ASSENT 3(一种新溶栓方案的安全性和有效性评估)和ENTIRE-TIMI 23(依诺肝素和替奈普酶联合或不联合糖蛋白IIb/IIIa抑制剂作为ST段抬高型心肌梗死的再灌注策略——心肌梗死溶栓)研究表明,依诺肝素与阿替普酶或替奈普酶联合使用至少与UFH等效(HART II和ENTIRE-TIMI 23),并且可能优于UFH(ASSENT 3)。依诺肝素通过每日两次皮下注射给药。相比之下,UFH通过静脉输注给药,这需要常规监测活化部分凝血活酶时间以确保维持足够的抗凝水平。在ESSENCE和TIMI 11B研究的急性期期间,接受依诺肝素治疗的患者大出血发生率与接受UFH治疗的患者相似。相比之下,在这些研究中,接受依诺肝素治疗的患者轻微出血发生率高于接受UFH治疗的患者。
ESSENCE、TIMI 11B和ASSENT 3研究的数据促使人们呼吁将已被证明优于UFH的那些低分子量肝素视为不稳定冠状动脉综合征抗凝治疗的首选药物。迄今为止,这些建议未反映在目前同等看待UFH和低分子量肝素的指南中。尽管如此,本综述中报告的临床数据支持依诺肝素用于治疗急性冠状动脉综合征。这些数据表明,依诺肝素相对于UFH标准治疗显示出某些临床和实际优势,并且代表了急性冠状动脉综合征治疗中的一项重要进展。