Turpie A G
McMaster University, Hamilton, Ont., Canada.
Haemostasis. 1997;27 Suppl 1:19-24. doi: 10.1159/000217478.
Thrombosis is responsible for most acute manifestations of coronary artery disease, including unstable angina and non-Q-wave myocardial infarction (MI). Antiplatelet therapy plays a major role in reducing the risk of ischaemic events in such patients. Since thrombin generation is key in the pathogenesis of thrombosis, recent studies have focussed on thrombin inhibition in the management of acute ischaemia. Heparin is the most widely used anticoagulant for acute management of thrombosis and is the treatment of choice in the prevention and treatment of venous thromboembolism. Heparin given in therapeutic doses intravenously has been shown to be more effective than aspirin at reducing the risk of death or MI in patients with unstable angina. Low-molecular-weight heparins (LMWHs) have improved pharmacologic and pharmacokinetic properties over standard heparin that may result in greater efficiency and safety. LMWH may be given in fixed doses subcutaneously without monitoring, resulting in greater clinical utility and cost-effectiveness compared with standard heparin. A number of LMWHs-dalteparin, enoxaparin and nadroparin-have been evaluated in unstable angina. In a small open trial, nadroparin reduced the risk of ischaemic outcomes compared with aspirin alone or a combination of aspirin and standard heparin. Dalteparin has been evaluated in two large clinical trials in the management of unstable angina. The low-Molecular-Weight Heparin (Fragmin) During Instability in Coronary Artery Disease (FRISC) trial showed that dalteparin resulted in a 63% reduction in risk of death or acute MI compared with aspirin alone. The Fragmin in Unstable Coronary Artery Disease (FRIC) trial showed that dalteparin was as effective as intravenous heparin. Enoxaparin resulted in a statistically significant 16% reduction in the combined outcome of death, MI and recurrence of angina in comparison with standard heparin in the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) trial. There is accumulating evidence that LMWHs are safe and effective alternatives to standard heparin in unstable coronary artery disease and that they offer practical and therapeutic advantages.
血栓形成是冠状动脉疾病大多数急性表现的原因，包括不稳定型心绞痛和非Q波心肌梗死（MI）。抗血小板治疗在降低此类患者缺血事件风险方面发挥着重要作用。由于凝血酶生成是血栓形成发病机制的关键，最近的研究集中在急性缺血管理中的凝血酶抑制。肝素是血栓形成急性管理中使用最广泛的抗凝剂，也是预防和治疗静脉血栓栓塞的首选治疗方法。静脉注射治疗剂量的肝素已被证明在降低不稳定型心绞痛患者死亡或心肌梗死风险方面比阿司匹林更有效。低分子量肝素（LMWHs）比标准肝素具有更好的药理学和药代动力学特性，这可能导致更高的效率和安全性。LMWH可以皮下固定剂量给药而无需监测，与标准肝素相比，具有更大的临床实用性和成本效益。多种LMWH——达肝素、依诺肝素和那屈肝素——已在不稳定型心绞痛中进行了评估。在一项小型开放试验中，与单独使用阿司匹林或阿司匹林与标准肝素联合使用相比，那屈肝素降低了缺血性结局的风险。达肝素已在两项治疗不稳定型心绞痛的大型临床试验中进行了评估。冠状动脉疾病不稳定期低分子量肝素（Fragmin）试验（FRISC）表明，与单独使用阿司匹林相比，达肝素使死亡或急性心肌梗死风险降低了63%。不稳定冠状动脉疾病中的Fragmin试验（FRIC）表明，达肝素与静脉注射肝素一样有效。在非Q波冠状动脉事件中皮下注射依诺肝素的疗效和安全性（ESSENCE）试验中，与标准肝素相比，依诺肝素使死亡、心肌梗死和心绞痛复发的综合结局在统计学上显著降低了16%。越来越多的证据表明，在不稳定型冠状动脉疾病中，LMWH是标准肝素安全有效的替代品，并且它们具有实际和治疗优势。
