Weaver W D, Hartmann J R, Anderson J L, Reddy P S, Sobolski J C, Sasahara A A
Myocardial Infarction Triage and Intervention (MITI) Project Group, University of Washington, Seattle.
J Am Coll Cardiol. 1994 Nov 1;24(5):1242-8. doi: 10.1016/0735-1097(94)90105-8.
Three dosage regimens of a new recombinant glycosylated prourokinase (A-74187) were evaluated by measuring coronary artery patency at 90 min in patients with acute myocardial infarction.
Prourokinase is a thrombolytic drug with unique pharmacologic properties that may be clinically advantageous.
Aspirin (325 mg), intravenous heparin and prourokinase (60- or 80-mg monotherapy or 60 mg "primed" with a preceding bolus dose of 250,000 IU of recombinant urokinase) were administered to 128 patients. Coronary angiography was performed at 60 min (wherever possible), 90 min (primary end point) and 24 h to determine arterial patency and reocclusion rates. Plasma was collected serially to measure fibrinogen, plasminogen, thrombin antithrombin III and fibrinopeptide A. Clinical events until hospital discharge were recorded.
The coronary artery patency rate at 90 min was similar for all three regimens, averaging 73% (95% confidence interval [CI] 64% to 80%); Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow rates averaged 52% (95% CI 42% to 61%). Arterial patency at 60 min was 62% (95% CI 50% to 73%), and reocclusion occurred in 1.4% (95% CI 0.1% to 4.1%). Prourokinase demonstrated relative fibrin specificity at all doses studied. Fibrinopeptide A and thrombin antithrombin III levels were elevated at baseline and declined rapidly during the 1st 12 h. There was no difference in the baseline values of these thrombin markers between patients with patent versus closed arteries at 90 min. There was one death; no strokes occurred.
A-74187 prourokinase is a rapid-acting, effective fibrin-specific thrombolytic agent. Reocclusion was unusual, possibly because of aggressive anticoagulation with intravenous heparin or unique features of the drug. Full definition of the clinical effectiveness of this drug merits examination in future randomized trials evaluating clinical and angiographic effectiveness.
通过测量急性心肌梗死患者90分钟时的冠状动脉通畅情况，对一种新型重组糖基化单链尿激酶原（A - 74187）的三种给药方案进行评估。
单链尿激酶原是一种具有独特药理特性的溶栓药物，可能具有临床优势。
对128例患者给予阿司匹林（325毫克）、静脉注射肝素和单链尿激酶原（60毫克或80毫克单一疗法，或60毫克先用250,000国际单位重组尿激酶推注进行“预充”）。在60分钟（尽可能）、90分钟（主要终点）和24小时进行冠状动脉造影，以确定动脉通畅率和再闭塞率。连续采集血浆以测量纤维蛋白原、纤溶酶原、凝血酶 - 抗凝血酶III和纤维肽A。记录直至出院的临床事件。
三种给药方案在90分钟时的冠状动脉通畅率相似，平均为73%（95%置信区间[CI]64%至80%）；心肌梗死溶栓（TIMI）3级血流率平均为52%（95%CI 42%至61%）。60分钟时的动脉通畅率为62%（95%CI 50%至73%），再闭塞发生率为1.4%（95%CI 0.1%至4.1%）。在所有研究剂量下，单链尿激酶原均表现出相对的纤维蛋白特异性。纤维肽A和凝血酶 - 抗凝血酶III水平在基线时升高，并在最初12小时内迅速下降。90分钟时动脉通畅与闭塞的患者之间，这些凝血酶标志物的基线值无差异。有1例死亡；未发生中风。
A - 74187单链尿激酶原是一种起效迅速、有效的纤维蛋白特异性溶栓剂。再闭塞不常见，可能是由于静脉注射肝素的积极抗凝作用或该药物的独特特性。该药物临床有效性的全面定义值得在未来评估临床和血管造影有效性的随机试验中进行研究。
