Cannon C P, McCabe C H, Diver D J, Herson S, Greene R M, Shah P K, Sequeira R F, Leya F, Kirshenbaum J M, Magorien R D
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
J Am Coll Cardiol. 1994 Dec;24(7):1602-10. doi: 10.1016/0735-1097(94)90163-5.
The aim of our study was to determine a superior thrombolytic regimen from three: anistreplase (APSAC), front-loaded recombinant tissue-type plasminogen activator (rt-PA) or combination thrombolytic therapy.
Although thrombolytic therapy has been shown to reduce mortality and morbidity after acute myocardial infarction, it has not been clear whether more aggressive thrombolytic-antithrombotic regimens could improve the outcome achieved with standard regimens.
To address this issue, 382 patients with acute myocardial infarction were randomized to receive in a double-blind fashion (along with intravenous heparin and aspirin) APSAC, front-loaded rt-PA or a combination of both agents. The primary end point "unsatisfactory outcome" was a composite clinical end point assessed through hospital discharge.
Patency of the infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) at 60 min after the start of thrombolysis was significantly higher in rt-PA-treated patients (77.8% vs. 59.5% for APSAC-treated patients and 59.3% for combination-treated patients [rt-PA vs. APSAC, p = 0.02; rt-PA vs. combination, p = 0.03]). At 90 min, the incidence of both infarct-related artery patency and TIMI grade 3 flow was significantly higher in rt-PA-treated patients (60.2% had TIMI grade 3 flow vs. 42.9% and 44.8% of APSAC- and combination-treated patients, respectively [rt-PA vs. APSAC, p < 0.01; rt-PA vs. combination, p = 0.02]). The incidence of unsatisfactory outcome was 41.3% for rt-PA compared with 49% for APSAC and 53.6% for the combination (rt-PA vs. APSAC, p = 0.19; rt-PA vs. combination, p = 0.06). The mortality rate at 6 weeks was lowest in the rt-PA-treated patients (2.2% vs. 8.8% for APSAC and 7.2% for combination thrombolytic therapy [rt-PA vs. APSAC, p = 0.02; rt-PA vs. combination, p = 0.06]).
Front-loaded rt-PA achieved significantly higher rates of early reperfusion and was associated with trends toward better overall clinical benefit and survival than those achieved with a standard thrombolytic agent or combination thrombolytic therapy. These findings support the concept that more rapid reperfusion of the infarct-related artery is associated with improved clinical outcome.
我们研究的目的是从三种溶栓方案中确定一种更优方案：茴酰化纤溶酶原链激酶激活剂复合物（APSAC）、负荷剂量重组组织型纤溶酶原激活剂（rt-PA）或联合溶栓治疗。
尽管溶栓治疗已被证明可降低急性心肌梗死后的死亡率和发病率，但更积极的溶栓-抗栓方案是否能改善标准方案的治疗效果尚不清楚。
为解决这一问题，382例急性心肌梗死患者被随机双盲接受（联合静脉肝素和阿司匹林）APSAC、负荷剂量rt-PA或两种药物联合治疗。主要终点“不满意结局”是一个通过出院时评估的综合临床终点。
溶栓开始后60分钟时，rt-PA治疗组梗死相关动脉通畅率（心肌梗死溶栓试验[TIMI]2级或3级血流）显著高于APSAC治疗组（77.8%对59.5%）和联合治疗组（59.3%）[rt-PA与APSAC相比，p = 0.02；rt-PA与联合治疗相比，p = 0.03]。90分钟时，rt-PA治疗组梗死相关动脉通畅率和TIMI 3级血流发生率均显著更高（60.2%有TIMI 3级血流，而APSAC治疗组和联合治疗组分别为42.9%和44.8%）[rt-PA与APSAC相比，p < 0.01；rt-PA与联合治疗相比，p = 0.02]。rt-PA组不满意结局发生率为41.3%，APSAC组为49%，联合治疗组为53.6%（rt-PA与APSAC相比，p = 0.19；rt-PA与联合治疗相比，p = 0.06）。rt-PA治疗组6周时死亡率最低（2.2%，而APSAC组为8.8%，联合溶栓治疗组为7.2%）[rt-PA与APSAC相比，p = 0.02；rt-PA与联合治疗相比，p = 0.06]。
负荷剂量rt-PA实现了显著更高的早期再灌注率，与标准溶栓剂或联合溶栓治疗相比，在总体临床获益和生存方面有更好趋势。这些发现支持梗死相关动脉更快再灌注与改善临床结局相关的概念。
