THROMBOLYSIS WITH RECOMBINANT UNGLYCOSYLATED SINGLE-CHAIN UROKINASE-TYPE PLASMINOGEN-ACTIVATOR (SARUPLASE) IN ACUTE MYOCARDIAL-INFARCTION - INFLUENCE OF HEPARIN ON EARLY PATENCY RATE (LIMITS STUDY)

Objectives. 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. Background. Heparin has been used after thrombolytic therapy for acute myocardial infarction to prevent reocclusion of the infarct related artery. Methods. 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. Results. In the HSH group (heparin-saruplase-heparin), 78.6% of patients had an open infarct-related vessel (Thrombolysis in Myocardial Infarction [TIMI] how 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%). Conclusions. 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.