N Engl J Med. 1997 Oct 16;337(16):1118-23. doi: 10.1056/NEJM199710163371603.
Reteplase (recombinant plasminogen activator), a mutant of alteplase tissue plasminogen activator, has a longer half-life than its parent molecule and produced superior angiographic results in pilot studies of acute myocardial infarction. In this large clinical trial, we compared the efficacy and safety of these two thrombolytic agents.
A total of 15,059 patients from 807 hospitals in 20 countries who presented within 6 hours after the onset of symptoms with ST-segment elevation or bundle-branch block were randomly assigned in a 2:1 ratio to receive reteplase, in two bolus doses or 10 MU each given 30 minutes apart, or an accelerated infusion of alteplase, up to 100 mg infused over a period of 90 minutes. The primary hypothesis was that mortality at 30 days would be significantly lower with reteplase.
The mortality rate at 30 days was 7.47 percent for reteplase and 7.24 percent for alteplase (adjusted P=0.54; odds ratio, 1.03; 95 percent confidence interval, 0.91 to 1.18). The 95 percent confidence interval for the absolute difference in mortality rates was -1.1 to 0.66 percent. Stroke occurred in 1.64 percent of patients treated with reteplase and in 1.79 percent of those treated with alteplase (P= 0.50). The respective rates of the combined end point of death or nonfatal, disabling stroke were 7.89 percent and 7.91 percent (P=0.97; odds ratio, 1.0; 95 percent confidence interval, 0.88 to 1.13).
As compared with an accelerated infusion of alteplase, reteplase, although easier to administer, did not provide any additional survival benefit in the treatment of acute myocardial infarction. Other results, particularly for the combined end point of death or nonfatal, disabling stroke, were remarkably similar for the two plasminogen activators.
瑞替普酶（重组纤溶酶原激活剂）是阿替普酶（组织纤溶酶原激活剂）的一种突变体，其半衰期比母体分子更长，并且在急性心肌梗死的初步研究中产生了更好的血管造影结果。在这项大型临床试验中，我们比较了这两种溶栓药物的疗效和安全性。
来自20个国家807家医院的15059例患者在症状发作后6小时内出现ST段抬高或束支传导阻滞，按2:1的比例随机分配，接受瑞替普酶治疗，分两次推注，每次10MU，间隔30分钟，或加速输注阿替普酶，在90分钟内输注高达100mg。主要假设是瑞替普酶治疗30天时的死亡率会显著降低。
瑞替普酶治疗30天的死亡率为7.47%，阿替普酶为7.24%（校正P=0.54；优势比，1.03；95%置信区间，0.91至1.18）。死亡率绝对差异的95%置信区间为-1.1至0.66%。接受瑞替普酶治疗的患者中有1.64%发生卒中，接受阿替普酶治疗的患者中有1.79%发生卒中（P=0.50）。死亡或非致死性致残性卒中联合终点的发生率分别为7.89%和7.91%（P=0.97；优势比，1.0；95%置信区间，0.88至1.13）。
与加速输注阿替普酶相比，瑞替普酶虽然给药更容易，但在急性心肌梗死治疗中并未提供任何额外的生存益处。两种纤溶酶原激活剂的其他结果，特别是死亡或非致死性致残性卒中联合终点的结果非常相似。
