N Engl J Med. 1997 Oct 16;337(16):1124-30. doi: 10.1056/NEJM199710163371604.
Accelerated infusion of alteplase (tissue plasminogen activator) over a period of 90 minutes induces more rapid lysis of coronary-artery thrombi than a 3-hour infusion. With two bolus doses of alteplase, further shortening the duration of administration, complete reperfusion was achieved in more than 85 percent of the patients in initial angiographic studies. We tested the hypothesis that double-bolus alteplase is at least as effective as accelerated infusion.
In 398 hospitals, 7169 patients with acute myocardial infarction were randomly assigned to weight-adjusted, accelerated infusion of 100 mg of alteplase or to a bolus of 50 mg of alteplase over a period of 1 to 3 minutes followed 30 minutes later by a second bolus of 50 mg (or 40 mg for patients who weighed less than 60 kg). The primary end point was death from any cause at 30 days. The trial was stopped prematurely because of concern about the safety of the double-bolus injection.
Thirty-day mortality was higher in the double-bolus group than in the accelerated-infusion group: 7.98 percent as compared with 7.53 percent. The absolute difference was 0.44 percent, with a one-sided 95 percent upper boundary of 1.49 percent, which exceeded the prespecified upper limit of 0.40 percent to indicate equivalence in 30-day mortality between the two regimens. The respective rates of any stroke and of hemorrhagic stroke were 1.92 and 1.12 percent after double-bolus alteplase, as compared with 1.53 and 0.81 percent after an accelerated infusion of alteplase (P=0.24 and P=0.23, respectively).
Double-bolus alteplase was not shown to be equivalent, according to the prespecified criteria, to accelerated infusion with regard to 30-day mortality. There was also a slightly higher rate of intracranial hemorrhage with the double-bolus method. Therefore, accelerated infusion of alteplase over a period of 90 minutes remains the preferred regimen.
与3小时输注相比，在90分钟内加速输注阿替普酶（组织纤溶酶原激活剂）能更快速地溶解冠状动脉血栓。在最初的血管造影研究中，使用两次推注剂量的阿替普酶，进一步缩短给药时间，超过85%的患者实现了完全再灌注。我们检验了双推注阿替普酶至少与加速输注一样有效的假设。
在398家医院，7169例急性心肌梗死患者被随机分配接受按体重调整的100mg阿替普酶加速输注，或在1至3分钟内推注50mg阿替普酶，30分钟后再推注50mg（体重小于60kg的患者为40mg）。主要终点是30天时任何原因导致的死亡。由于担心双推注注射的安全性，试验提前终止。
双推注组30天死亡率高于加速输注组：分别为7.98%和7.53%。绝对差异为0.44%，单侧95%上限为1.49%，超过了预先设定的0.40%上限，该上限用于表明两种方案30天死亡率的等效性。双推注阿替普酶后任何卒中及出血性卒中的发生率分别为1.92%和1.12%，而加速输注阿替普酶后分别为1.53%和0.81%（P分别为0.24和0.23）。
根据预先设定的标准，双推注阿替普酶在30天死亡率方面与加速输注不等效。双推注方法导致的颅内出血发生率也略高。因此，90分钟内加速输注阿替普酶仍是首选方案。
