Thrombolysis with recombinant unglycosylated single-chain urokinase-type plasminogen activator (saruplase) in acute myocardial infarction : influence of heparin on early patency rate (LIMITS study)

Abstract 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] 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%). 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.