Tebbe U, Windeler J, Boesl I, Hoffmann H, Wojcik J, Ashmawy M, Rüdiger Schwarz E, von Loewis P, Rosemeyer P, Hopkins G
Gruenenthal GmbH, Aachen, Germany.
J Am Coll Cardiol. 1995 Aug;26(2):365-73. doi: 10.1016/0735-1097(95)80008-5.
The Liquemin in Myocardial Infarction During Thrombolysis With Saruplase (LIMITS) study was instituted to evaluate and characterize the effect of a prethrombolytic heparin bolus (5,000 IU) on the efficacy and safety of saruplase in patients with acute myocardial infarction.
Heparin has been used after thrombolytic therapy for acute myocardial infarction to prevent reocclusion of the infarct-related artery.
The study was designed as a randomized, parallel-group, double-blind, multicenter trial. Patients were treated within 6 h of onset of symptoms with either a bolus of 5,000 IU of heparin (Liquemin) (n = 56, HSH group) or placebo (n = 62, PSH group) before thrombolytic treatment with saruplase given as a 20-mg bolus followed by an infusion of 60 mg over 60 min. Thirty minutes after completion of thrombolysis, an intravenous heparin infusion was administered for 5 days. Before coronary angiography was performed at 6 to 12 h after start of lysis, an additional bolus of 5,000 IU heparin was given to all patients. End points studied were patency of the infarct-related artery, changes in the hemostatic system and bleeding complications.
In the HSH group (heparin-saruplase-heparin), 78.6% of patients had an open infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] flow grade 2 or 3) compared with 56.5% in the PSH group (placebo-saruplase-heparin) (intention-to-treat analysis, p = 0.01). No significant difference was observed between the two groups with regard to changes in fibrinogen and fibrin/fibrinogen degradation products. A total of eight bleeding complications (14.3%) were observed in the HSH group and five (8.1%) in the PSH group; no cerebrovascular event occurred, and no allergic reaction was reported. A total of 12 patients died during the hospital stay, 3 in the HSH group (5.4%) and 9 in the PSH group (14.5%).
In acute myocardial infarction, the administration of a heparin bolus before thrombolytic therapy with saruplase is associated with a significantly higher patency at angiography 6 to 12 h after the start of thrombolysis without any appreciable increase in risk of bleeding.
开展纤溶酶原激活剂溶栓治疗急性心肌梗死期间使用肝素（LIMITS）研究，以评估和描述溶栓前静脉推注肝素（5000IU）对急性心肌梗死患者使用纤溶酶原激活剂的疗效和安全性的影响。
肝素已用于急性心肌梗死后的溶栓治疗，以防止梗死相关动脉再闭塞。
该研究设计为一项随机、平行组、双盲、多中心试验。症状发作6小时内的患者，在使用纤溶酶原激活剂进行溶栓治疗前，随机接受5000IU肝素静脉推注（力抗栓）（n = 56，HSH组）或安慰剂（n = 62，PSH组），纤溶酶原激活剂以20mg静脉推注给药，随后在60分钟内输注60mg。溶栓完成30分钟后，静脉输注肝素5天。在溶栓开始后6至12小时进行冠状动脉造影前，所有患者均额外静脉推注5000IU肝素。研究的终点是梗死相关动脉的通畅情况、止血系统的变化和出血并发症。
在HSH组（肝素-纤溶酶原激活剂-肝素）中，78.6%的患者梗死相关血管通畅（心肌梗死溶栓[TIMI]血流分级为2级或3级），而PSH组（安慰剂-纤溶酶原激活剂-肝素）为56.5%（意向性分析，p = 0.01）。两组之间纤维蛋白原和纤维蛋白/纤维蛋白原降解产物的变化无显著差异。HSH组共观察到8例出血并发症（14.3%），PSH组观察到5例（8.1%）；未发生脑血管事件，也未报告过敏反应。住院期间共有12例患者死亡，HSH组3例（5.4%），PSH组9例（14.5%）。
在急性心肌梗死中，溶栓治疗前静脉推注肝素与溶栓开始后6至12小时血管造影时更高的血管通畅率相关，且出血风险无明显增加。
