Background: We undertook an angiographic, dose-finding study of staphylokinase (SAK42D variant) to evaluate its efficacy and safety in patients with acute ST-segment myocardial infarction.
Methods and results: Patients were studied within 6 hours of symptom onset and received SAK42D as a 30-minute infusion with 20% of the total dose given as a bolus. Eighty-two patients with a median age of 60 years (interquartile range 52 to 69 years), 84% male and 43% with an anterior myocardial infarction, were studied at a median time from symptom onset of 2.7 hours. There was a high degree of Thrombolysis in Myocardial Infarction (TIMI) 3 flow achieved with 15 mg of SAK42D, that is, 62%. Therefore after 21 patients had been studied at this dose the next dose of 30 mg was used and 65% TIMI 3 patency was achieved. At the peak dose of 45 mg, TIMI 3 90-minute patency was 63%. There were no allergic reactions, and no patient had intracranial hemorrhage. Four patients had major and 9 moderate bleeding during the study; 2 of the major and 5 of the moderate bleeding events occurred within 48 hours of commencement of treatment. The majority (62%) of these were related to vascular instrumentation, and there was no relation between the extent of bleeding and dose of SAK42D used. Forty-five minutes after cessation of SAK42D, there were small percent decrements in plasma fibrinogen and plasminogen levels that did not reach statistical significance. However, there were dose-related changes in alpha(2) anti-plasmin that revealed a borderline significant reduction that was dose related (P =.053).
Conclusion: These data revealed similar fibrinolytic efficacy across a 3-fold increment in dose, indicating that this study operated on a flat portion of the dose-response curve. The favorable efficacy/safety profile achieved with staphylokinase is encouraging, and further investigation is warranted.