Montalescot Gilles, White Harvey D, Gallo Richard, Cohen Marc, Steg P Gabriel, Aylward Philip E G, Bode Christoph, Chiariello Massimo, King Spencer B, Harrington Robert A, Desmet Walter J, Macaya Carlos, Steinhubl Steven R
Institut de Cardiologie, Centre Hospitalier Universitaire Pitié-Salpêtrière, Paris, France.
N Engl J Med. 2006 Sep 7;355(10):1006-17. doi: 10.1056/NEJMoa052711.
Despite its limitations, unfractionated heparin has been the standard anticoagulant used during percutaneous coronary intervention (PCI). Several small studies have suggested that intravenous enoxaparin may be a safe and effective alternative. Our primary aim was to assess the safety of enoxaparin as compared with that of unfractionated heparin in elective PCI.
In this prospective, open-label, multicenter, randomized trial, we randomly assigned 3528 patients with PCI to receive enoxaparin (0.5 or 0.75 mg per kilogram of body weight) or unfractionated heparin adjusted for activated clotting time, stratified according to the use or nonuse of glycoprotein IIb/IIIa inhibitors. The primary end point was the incidence of major or minor bleeding that was not related to coronary-artery bypass grafting. The main secondary end point was the percentage of patients in whom the target anticoagulation levels were reached.
Enoxaparin at a dose of 0.5 mg per kilogram was associated with a significant reduction in the rate of non-CABG-related bleeding in the first 48 hours, as compared with unfractionated heparin (5.9% vs. 8.5%; absolute difference, -2.6; 95% confidence interval [CI], -4.7 to -0.6; P=0.01), but the higher enoxaparin dose was not (6.5% vs. 8.5%; absolute difference, -2.0; 95% CI, -4.0 to 0.0; P=0.051). The incidence of major bleeding was significantly reduced in both enoxaparin groups, as compared with the unfractionated heparin group. Target anticoagulation levels were reached in significantly more patients who received enoxaparin (0.5-mg-per-kilogram dose, 79%; 0.75-mg-per-kilogram dose, 92%) than who received unfractionated heparin (20%, P<0.001).
In elective PCI, a single intravenous bolus of 0.5 mg of enoxaparin per kilogram is associated with reduced rates of bleeding, and a dose of 0.75 mg per kilogram yields rates similar to those for unfractionated heparin, with more predictable anticoagulation levels. The trial was not large enough to provide a definitive comparison of efficacy in the prevention of ischemic events. (ClinicalTrials.gov number, NCT00077844 [ClinicalTrials.gov].).
尽管普通肝素存在局限性，但它一直是经皮冠状动脉介入治疗（PCI）期间使用的标准抗凝剂。多项小型研究表明，静脉注射依诺肝素可能是一种安全有效的替代药物。我们的主要目的是评估在择期PCI中，依诺肝素与普通肝素相比的安全性。
在这项前瞻性、开放标签、多中心、随机试验中，我们将3528例接受PCI的患者随机分配，使其接受依诺肝素（0.5或0.75毫克/千克体重）或根据活化凝血时间调整剂量的普通肝素，并根据是否使用糖蛋白IIb/IIIa抑制剂进行分层。主要终点是与冠状动脉旁路移植术无关的严重或轻微出血的发生率。主要次要终点是达到目标抗凝水平的患者百分比。
与普通肝素相比，每千克体重0.5毫克剂量的依诺肝素在最初48小时内与非冠状动脉旁路移植术相关出血率的显著降低相关（5.9%对8.5%；绝对差异为-2.6；95%置信区间[CI]，-4.7至-0.6；P = 0.01），但较高剂量的依诺肝素则不然（6.5%对8.5%；绝对差异为-2.0；95% CI，-4.0至0.0；P = 0.051）。与普通肝素组相比，两个依诺肝素组的严重出血发生率均显著降低。接受依诺肝素（每千克体重0.5毫克剂量，79%；每千克体重0.75毫克剂量，92%）的患者达到目标抗凝水平的比例显著高于接受普通肝素的患者（20%，P<0.001）。
在择期PCI中，每千克体重单次静脉推注0.5毫克依诺肝素与出血率降低相关，每千克体重0.75毫克的剂量产生的出血率与普通肝素相似，且抗凝水平更可预测。该试验规模不足以对预防缺血事件的疗效进行明确比较。（ClinicalTrials.gov编号，NCT00077844 [ClinicalTrials.gov]。）
