Background The success of streptokinase in acute myocardial infarction is hampered by the high failure rate to achieve early reperfusion. This study evaluates the possible benefit of Hirulog (Biogen, Cambridge, Mass), a direct thrombin inhibitor, as adjunct therapy to streptokinase to enhance early patency and prevent rethrombosis. Heparin has been shown to be of very limited benefits in this setting.Methods and Results Forty-five patients were randomized to Hirulog or heparin (2:1 ratio). Coronary angiography documented a TIMI 2 or 3 flow after 90 minutes in 77% of the patients treated with Hirulog and streptokinase and in 47% of patients treated with heparin and streptokinase (P<.05) and after 120 minutes in 87% and 47% of patients, respectively (P<.01). TIMI 3 flow was established in 77% of patients with Hirulog compared with 40% with heparin (P<.02). The clinical outcome and the bleeding rate were also favorable to Hirulog; no reocclusion was observed at late angiography performed 4.7 days later.Conclusions Hirulog in this pilot study significantly improved the early patency rate of the infarct-related artery with a favorable clinical profile. This new direct thrombin inhibitor exhibits promise as adjunctive therapy to thrombolysis. (Circulation. 1994;89:1567-1572.)