Lancet. 1999 Feb 6;353(9151):429-38.
Despite the use of heparin and aspirin, 5-10% of patients with unstable angina develop myocardial infarction or refractory angina in hospital. We tested the hypothesis that recombinant hirudin (lepirudin), a direct thrombin inhibitor, would be superior to heparin, an indirect thrombin inhibitor, in patients with acute ischaemic syndromes who were receiving aspirin.
10,141 patients with unstable angina or suspected acute myocardial infarction without ST elevation were randomly assigned heparin (5000 units bolus then 15 units kg(-1) h(-1); n=5058) or hirudin (0.4 mg/kg bolus then 0.15 mg kg(-1) h(-1) infusion; n=5083) for 72 h in a double-blind trial. The primary outcome measure was cardiovascular death or new myocardial infarction at 7 days. Analysis was by intention to treat.
At 7 days, 213 (4.2%) patients in the heparin group and 182 (3.6%) in the hirudin group had experienced cardiovascular death or new myocardial infarction (relative risk 0.84 [95% CI 0.69-1.02]; p=0.077). The numbers with cardiovascular death, new myocardial infarction, or refractory angina at 7 days were 340 (6.7%) with heparin and 284 (5.6%) with hirudin (0.82 [0.70-0.96]; p=0.0125). These differences were primarily observed during the 72 h treatment period (cardiovascular death or myocardial infarction relative risk 0.76 [0.59-0.99], p=0.039: cardiovascular death, myocardial infarction, or refractory angina 0.78 [0.63-0.96], p=0.019). Although there was an excess of major bleeding requiring transfusion with hirudin (59 [1.2%] vs 34 [0.7%] with heparin; p=0.01), there was no excess in life-threatening episodes (20 in each group) or strokes (14 in each group).
The data from OASIS-2 suggest that recombinant hirudin is superior to heparin in preventing cardiovascular death, myocardial infarction, and refractory angina with an acceptable safety profile in patients with unstable angina or acute myocardial infarction without ST elevation. Thus, a direct thrombin inhibitor is more effective than an indirect thrombin inhibitor.
尽管使用了肝素和阿司匹林，但仍有5% - 10%的不稳定型心绞痛患者在住院期间发生心肌梗死或难治性心绞痛。我们检验了这样一个假设：对于正在服用阿司匹林的急性缺血综合征患者，直接凝血酶抑制剂重组水蛭素（lepirudin）优于间接凝血酶抑制剂肝素。
10141例无ST段抬高的不稳定型心绞痛或疑似急性心肌梗死患者在一项双盲试验中被随机分配接受肝素（静脉推注5000单位，然后以15单位·kg⁻¹·h⁻¹持续静脉滴注；n = 5058）或水蛭素（静脉推注0.4mg/kg，然后以0.15mg·kg⁻¹·h⁻¹持续静脉滴注；n = 5083）治疗72小时。主要结局指标为7天时的心血管死亡或新发心肌梗死。分析采用意向性分析。
7天时，肝素组有213例（4.2%）患者发生心血管死亡或新发心肌梗死，水蛭素组有182例（3.6%）（相对风险0.84 [95%可信区间0.69 - 1.02]；p = 0.077）。7天时发生心血管死亡、新发心肌梗死或难治性心绞痛的患者数量，肝素组为340例（6.7%），水蛭素组为284例（5.6%）（0.82 [0.70 - 0.96]；p = 0.0125）。这些差异主要在72小时治疗期间观察到（心血管死亡或心肌梗死相对风险0.76 [0.59 - 0.99]，p = 0.039；心血管死亡、心肌梗死或难治性心绞痛0.78 [0.63 - 0.96]，p = 0.019）。尽管使用水蛭素后需要输血的严重出血事件有所增加（59例 [1.2%] 对比肝素组的34例 [0.7%]；p =
