Streptokinase is a thrombolytic agent derived originally from streptococcal bacteria. It needs to combine with plasminogen to form an activated complex, which subsequently acts to activate another plasminogen molecule, ie it requires two plasminogen molecules to produce one plasmin. A pharmacological variant is Apsac which is an activated complex of plasminogen and streptokinase, stabilised with an acyl group.
Streptokinase activation of plasminogen occurs in an environment probably hostile to the streptokinase - most individuals have antibodies to streptokinase as a result of streptococcal infection and a few 100,000 molecules are needed to neutralise these antibodies. There is thus a bell shaped dose response curve, and in the first 24 hours, nearly all plasminogen disappears.
Two placebo-controlled trials were instrumental in establishing the efficacy of streptokinase in reducing mortality. The GISSI trial (published in 1986) included 11,712 patients, and the ISIS-2 trial (published in 1988) included 17,187 patients. In the GISSI study, 21-day mortality was 10.7% in patients treated with streptokinase and 13% in those treated with placebo. This represents a statistically significant absolute reduction of 2.3% (risk ratio 0.81; 95% confidence ratio [CI] 0.72 to 0.9). In the ISIS-2 study, vascular mortality at 5 weeks was 9.2% in patients treated with streptokinase and 12% in those treated with placebo. This represents a statistically significant absolute reduction of 2.8%. These benefits were independent of those of early aspirin treatment.
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