Goodman Shaun G, Fitchett David, Armstrong Paul W, Tan Mary, Langer Anatoly
Canadian Heart Research Centre and Terrence Donnelly Heart Centre, Division of Cardiology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Circulation. 2003 Jan 21;107(2):238-44. doi: 10.1161/01.cir.0000050144.67910.13.
Current pharmacotherapeutic options for high-risk non-ST-segment elevation acute coronary syndrome patients include aspirin, clopidogrel, heparin, and platelet glycoprotein IIb/IIIa inhibition. A key issue of uncertainty is the safety and efficacy of combination glycoprotein IIb/IIIa inhibitor and low-molecular-weight heparin therapy.
We randomized 746 patients with rest ischemic discomfort within 24 hours after the onset of symptoms and ST-segment deviation and/or elevation of serum cardiac markers to receive open-label enoxaparin (1 mg/kg subcutaneously twice daily) or unfractionated heparin (70-U/kg bolus; 15 U x kg(-1) x h(-1) infusion, titrated to an activated partial thromboplastin time of 1.5 to 2 times control) for 48 hours. All patients received aspirin and eptifibatide (180- microg/kg bolus; 2 microg x kg(-1) x min(-1) infusion). Major non-coronary artery bypass surgery-related bleeding at 96 hours (primary safety outcome) was significantly lower among enoxaparin-treated patients than among heparin-treated patients (1.8% versus 4.6%, P=0.03). Minor bleeding was more frequent in the enoxaparin group (30.3% versus 20.8%, P=0.003). Patients in the enoxaparin group were less likely to experience ischemia as detected by continuous ECG evaluation (primary efficacy outcome) during the initial (14.3% versus 25.4%, P=0.0002) and subsequent (12.7% versus 25.9%, P<0.0001) 48-hour monitoring periods. Death or myocardial infarction at 30 days was significantly lower in the enoxaparin group (5% versus 9%, P=0.031).
When aspirin and eptifibatide are used in high-risk non-ST-segment elevation acute coronary syndrome patients, enoxaparin improves outcomes (determined on the basis of better safety and efficacy) compared with currently recommended unfractionated heparin therapy and provides a useful novel alternative therapeutic strategy.
目前针对高危非ST段抬高型急性冠脉综合征患者的药物治疗选择包括阿司匹林、氯吡格雷、肝素以及血小板糖蛋白IIb/IIIa抑制。一个关键的不确定问题是糖蛋白IIb/IIIa抑制剂与低分子量肝素联合治疗的安全性和有效性。
我们将746例在症状发作后24小时内有静息性缺血性不适且伴有ST段偏移和/或血清心肌标志物升高的患者随机分组，分别接受开放标签的依诺肝素（1mg/kg皮下注射，每日两次）或普通肝素（70U/kg静脉推注；15U·kg⁻¹·h⁻¹静脉输注，调整至活化部分凝血活酶时间为对照值的1.5至2倍）治疗48小时。所有患者均接受阿司匹林和依替巴肽（180μg/kg静脉推注；2μg·kg⁻¹·min⁻¹静脉输注）治疗。依诺肝素治疗的患者96小时时主要非冠状动脉搭桥手术相关出血（主要安全性结局）显著低于肝素治疗的患者（1.8%对4.6%，P = 0.03）。依诺肝素组轻微出血更常见（30.3%对20.8%，P = 0.003）。在初始（14.3%对25.4%，P = 0.0002）和随后（12.7%对25.9%，P < 0.0001）的48小时监测期内，依诺肝素组患者经连续心电图评估检测到缺血（主要有效性结局）的可能性较小。依诺肝素组30天时死亡或心肌梗死发生率显著低于肝素组（5%对9%，P = 0.031）。
当阿司匹林和依替巴肽用于高危非ST段抬高型急性冠脉综合征患者时，与目前推荐的普通肝素治疗相比，依诺肝素可改善结局（基于更好的安全性和有效性判定），并提供了一种有用的新型替代治疗策略。
