OBJECTIVE This study sought to demonstrate the equivalence of saruplase and streptokinase in terms of 30-day mortality. BACKGROUND The use of thrombolytic agents in the treatment of acute myocardial infarction is well established and has been shown to substantially reduce post-myocardial infarction mortality. METHODS Three thousand eighty-nine patients with symptoms compatible with those of acute myocardial infarction for < 6 h entered the study at a total of 104 centers and were randomized to receive streptokinase (1.5-MU infusion over 60 min) or saruplase (20-mg bolus and 60-mg infusion over 60 min). In the saruplase group, a bolus of heparin (5,000 IU) was administered before saruplase, and a corresponding blinded double-dummy placebo bolus was administered before streptokinase. All patients received intravenous heparin infusions for > or = 24 h starting 30 min after the end of the thrombolytic infusions; the infusions were titrated to maintain an activated partial thromboplastin time at 1.5 to 2.5 times that of normal. RESULTS Death of any cause up to 30 days after randomization occurred in 88 (5.7%) of 1,542 patients randomized to receive saruplase and 104 (6.7%) of 1,547 patients randomized to receive streptokinase (odds ratio 0.84, p < 0.01 for equivalence). Hemorrhagic strokes occurred more often in patients receiving saruplase (0.9% vs. 0.3%), whereas thromboembolic strokes were more prevalent in the streptokinase-treated patients (0.5% vs. 1.0%). The rate of bleeding was similar in the two treatment groups (10.4% vs. 10.9%). Hypotension and cardiogenic shock occurred less frequently in the saruplase group. Reinfarction rates were similar. CONCLUSIONS Saruplase is a clinically safe and effective thrombolytic medication. This profile ranks saruplase favorably among the currently available thrombolytic agents.