低分子量肝素与抗血小板药物联合用于非ST段抬高型急性冠状动脉综合征:最新进展
Combination of low molecular weight heparins with antiplatelet agents in non-ST elevation acute coronary syndromes: an update.
作者信息
Cohen Marc
机构信息
Division of Cardiology, MCP-Hahnemann School of Medicine, Philadelphia, Pennsylvania 19102-1192, USA.
出版信息
Drugs. 2002;62(12):1755-70. doi: 10.2165/00003495-200262120-00005.
This article reviews the use of low molecular weight heparin (LMWH) and antiplatelet agents in the treatment of unstable angina and non-ST segment elevation myocardial infarction (NSTEMI), which together account for 1 million hospitalisations annually in the US alone. Mortality and recurrent myocardial infarction (MI) in these conditions is currently approximately 8 to 16% at 1 month, and there is a need to optimise treatment further. Since their introduction, LMWHs have been shown to be successful and well tolerated in the treatment of unstable angina and NSTEMI, but differences have been seen in their efficacy compared with the parent compound, unfractionated heparin (UFH). A meta-analysis of all LMWHs, grouped, versus UFH showed equivalent efficacy and safety. The LMWHs dalteparin sodium and nadroparin calcium have independently been shown to be as effective as UFH. However, enoxaparin sodium has been shown to have greater clinical efficacy than UFH in patients with unstable angina (UA)/NSTEMI. One area of new research is patients with UA/NSTEMI who later undergo percutaneous coronary interventions (PCI), and early data suggest enoxaparin can be safely used as an anticoagulant instead of UFH in these patients. There is a wealth of data for glycoprotein (GP) IIb/IIIa receptor antagonists (abciximab, eptifibatide, lamifiban, and tirofiban), although some are conflicting. Recent meta-analyses suggest that some benefit is conferred by using these compounds, particularly in patients who undergo PCI. Recent trials have focussed on combining GP IIb/IIIa antagonists with LMWH, and although data is still scant, the ACUTE (Anti-thrombotic Combination Using Tirofiban and Enoxaparin) and ACUTE II studies indicate the safety and potential clinical benefit of combining enoxaparin with tirofiban in patients with UA/NSTEMI not undergoing PCI, compared with UFH and tirofiban. The NICE (National Investigators Collaborating on Enoxaparin) 4 study collected data on the combination of enoxaparin and abciximab in patients undergoing PCI, and both safety and efficacy data compared well with historical data collected on the use of UFH with abciximab. The more recent NICE 3 study extended this finding to the combination of enoxaparin with abciximab, tirofiban or eptifibatide. The safety of two doses of dalteparin and abciximab had also been investigated, with the higher dose the efficacious, and also with safety, in patients undergoing PCI. In addition, a GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes) IV substudy found that dalteparin had equivalent safety to UFH when co-administered with abciximab in patients not undergoing PCI. The NICE 3 and 4 trials were not randomised comparisons, and as such there results must be interpreted with caution. Recently, the CRUISE (Coronary Revascularisation Utilizing Integrelin [eptifibatide] and Single-bolus Enoxaparin) and INTERACT (Integrelin and Enoxaparin randomised assessment of Acute Coronary Syndromes Treatment) studies have provided evidence for both the safety and efficacy of enoxaparin combined with eptifibatide in non-ST elevation patients with acute coronary syndromes. A further study (SYNERGY [Superior Yield of the New strategy of Enoxaparin, Revascularization and GlYcoprotein IIb/IIIa inhibitors]) will investigate the efficacy of the combination of enoxaparin with abciximab versus that of UFH and abciximab in a large cohort of 8000 patients. The use of GP IIb/IIIa agents and LMWH in patients with UA/STEMI has led to their use in those with ST-elevation MI, and studies indicate LMWH is efficacious and can be used safely as an adjunct to thrombolysis. New studies will investigate the use of these agents in patients with STEMI not undergoing thrombolysis and we await the results of these studies.
本文综述了低分子量肝素(LMWH)和抗血小板药物在不稳定型心绞痛和非ST段抬高型心肌梗死(NSTEMI)治疗中的应用,仅在美国,这两种疾病每年就导致100万例住院治疗。目前,这些疾病在1个月时的死亡率和复发性心肌梗死(MI)约为8%至16%,因此有必要进一步优化治疗。自引入以来,LMWH已被证明在不稳定型心绞痛和NSTEMI的治疗中是成功的且耐受性良好,但与母体化合物普通肝素(UFH)相比,其疗效存在差异。一项对所有LMWH与UFH进行分组比较的荟萃分析显示,二者疗效和安全性相当。达肝素钠和那屈肝素钙已被独立证明与UFH疗效相当。然而,依诺肝素钠在不稳定型心绞痛(UA)/NSTEMI患者中已被证明比UFH具有更高的临床疗效。一个新的研究领域是UA/NSTEMI患者随后接受经皮冠状动脉介入治疗(PCI)的情况,早期数据表明依诺肝素可安全地用作这些患者的抗凝剂,替代UFH。关于糖蛋白(GP)IIb/IIIa受体拮抗剂(阿昔单抗、依替巴肽、拉米非班和替罗非班)有大量数据,尽管有些相互矛盾。最近的荟萃分析表明,使用这些化合物有一定益处,特别是在接受PCI的患者中。最近的试验集中在将GP IIb/IIIa拮抗剂与LMWH联合使用,尽管数据仍然稀少,但ACUTE(使用替罗非班和依诺肝素的抗血栓组合)和ACUTE II研究表明,与UFH和替罗非班相比,依诺肝素与替罗非班联合用于未接受PCI的UA/NSTEMI患者具有安全性和潜在的临床益处。NICE(国家依诺肝素研究协作组)4研究收集了接受PCI患者中依诺肝素与阿昔单抗联合使用的数据,其安全性和疗效数据与使用UFH和阿昔单抗收集的历史数据相比良好。更近的NICE 3研究将这一发现扩展到依诺肝素与阿昔单抗、替罗非班或依替巴肽的联合使用。还研究了两种剂量的达肝素与阿昔单抗的安全性,较高剂量在接受PCI的患者中有效且安全。此外,GUSTO(急性冠状动脉综合征中开放闭塞冠状动脉策略的全球应用)IV子研究发现,在未接受PCI的患者中,达肝素与阿昔单抗联合使用时与UFH安全性相当。NICE 3和4试验不是随机对照比较,因此其结果必须谨慎解读。最近,CRUISE(利用依替巴肽[依替巴肽]和单次推注依诺肝素进行冠状动脉血运重建)和INTERACT(依替巴肽和依诺肝素对急性冠状动脉综合征治疗的随机评估)研究为依诺肝素与依替巴肽联合用于非ST段抬高急性冠状动脉综合征患者的安全性和疗效提供了证据。另一项研究(SYNERGY[依诺肝素、血运重建和糖蛋白IIb/IIIa抑制剂新策略的卓越疗效])将在8000名患者的大型队列中研究依诺肝素与阿昔单抗联合使用相对于UFH与阿昔单抗联合使用的疗效。在UA/STEMI患者中使用GP IIb/IIIa药物和LMWH已导致其在ST段抬高型心肌梗死患者中的应用,研究表明LMWH有效且可安全地用作溶栓的辅助药物。新的研究将调查这些药物在未接受溶栓的STEMI患者中的应用,我们期待这些研究的结果。