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依诺肝素、达肝素与普通肝素对不稳定型心绞痛或非ST段抬高型急性心肌梗死患者血细胞活化标志物影响的比较(ARMADA研究)

Comparison of effects on markers of blood cell activation of enoxaparin, dalteparin, and unfractionated heparin in patients with unstable angina pectoris or non-ST-segment elevation acute myocardial infarction (the ARMADA study).

作者信息

Montalescot Gilles, Bal-dit-Sollier Claire, Chibedi Daniela, Collet Jean-Philippe, Soulat Thierry, Dalby Miles, Choussat Rémi, Cohen Ariel, Slama Michel, Steg Phillipe-Gabriel, Dubois-Randé Jean-Luc, Metzger Jean-Philippe, Tarragano François, Guermonprez Jean L, Drouet Ludovic

机构信息

Institut de Cardiologie, Bureau 2-236, Groupe Hospitalier Pitié-Salpêtrière Hospital, AP-HP, 47 Boulevard de l'Hôpital, 75013 Paris, France.

出版信息

Am J Cardiol. 2003 Apr 15;91(8):925-30. doi: 10.1016/s0002-9149(03)00105-x.

Abstract

The low-molecular-weight heparins (LMWHs) enoxaparin and dalteparin have shown superior and equivalent efficacy, respectively, over unfractionated heparin (UFH) in patients with unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI). This study aimed to identify markers of blood cell activation that are independent predictors of outcomes at 1 month and to compare the effects of enoxaparin, dalteparin, and UFH on any such markers. In this multicenter, prospective, open-label study, 141 patients with UAP or NSTEMI were randomized to treatment for 48 to 120 hours with enoxaparin (n = 46), dalteparin (n = 48), or UFH (n = 47). Blood samples were taken at the time of randomization and after > or =48 hours of treatment but before catheterization. Multivariate analysis identified increased plasma levels of von Willebrand factor (vWF) and decreased platelet levels of glycoprotein Ib/IX complexes as independent predictors of 1-month adverse outcome (a composite of death, myocardial infarction, and recurrent ischemia). vWF release was strongly related to and may have been released by inflammation as measured by C-reactive protein. Both LMWHs reduced the release of vWF in plasma (as well as C-reactive protein) compared with UFH. Enoxaparin had a more favorable effect on glycoprotein Ib/IX complexes than either dalteparin or UFH. The incidence of the composite clinical efficacy end point was: 13% (enoxaparin), 19% (dalteparin), and 28% (UFH). vWF and its receptor glycoprotein Ib/IX play a key role in acute coronary syndromes. vWF is linked to inflammation and, like glycoprotein Ib/IX, is affected more favorably by the LWMHs than by UFH.

摘要

低分子量肝素依诺肝素和达肝素,在不稳定型心绞痛(UAP)或非ST段抬高型心肌梗死(NSTEMI)患者中,分别显示出优于普通肝素(UFH)和与之等效的疗效。本研究旨在确定血细胞活化标志物,这些标志物是1个月时预后的独立预测指标,并比较依诺肝素、达肝素和普通肝素对任何此类标志物的影响。在这项多中心、前瞻性、开放标签研究中,141例UAP或NSTEMI患者被随机分为三组,分别接受依诺肝素(n = 46)、达肝素(n = 48)或普通肝素(n = 47)治疗48至120小时。在随机分组时以及治疗≥48小时后但在导管插入术前采集血样。多变量分析确定,血管性血友病因子(vWF)血浆水平升高和血小板糖蛋白Ib/IX复合物水平降低是1个月不良预后(死亡、心肌梗死和复发性缺血的综合指标)的独立预测因素。vWF释放与炎症密切相关,并且可能由炎症释放,炎症通过C反应蛋白测量。与普通肝素相比,两种低分子量肝素均降低了血浆中vWF的释放(以及C反应蛋白)。依诺肝素对糖蛋白Ib/IX复合物的影响比达肝素或普通肝素更有利。复合临床疗效终点的发生率分别为:13%(依诺肝素)、19%(达肝素)和28%(普通肝素)。vWF及其受体糖蛋白Ib/IX在急性冠状动脉综合征中起关键作用。vWF与炎症相关,并且与糖蛋白Ib/IX一样,低分子量肝素对其影响比普通肝素更有利。

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