Thrombolysis in acute myocardial infarction: analysis of studies comparing accelerated t-PA and streptokinase

To compare outcomes from accelerated alteplase (recombinant tissue plasminogen activator, t-PA) and streptokinase use in acute myocardial infarction.

Review of available studies identified by Medline and other literature searches that met the criteria of being a prospective, randomised clinical trial enrolling over 1000 patients with acute myocardial infarction. The studies had to contain an intervention arm comprising accelerated infusion t-PA, or an intervention arm comprising streptokinase provided accelerated t-PA that was compared in the same trial. Interventions compared were streptokinase 1.5 million units given over one hour compared with accelerated t-PA infusion, with concomitant use of aspirin and heparin, and main outcome measure of 30 day mortality.

Four studies met prespecified criteria, these being the GUSTO I, GUSTO IIb Angioplasty Substudy, GUSTO III, and COBALT trials. There was a total study population of 64,387 patients of whom 20,251 received streptokinase, 19,474 received t-PA, with others receiving different treatment. Pooled data show that accelerated t-PA produces a marginal 30 day mortality advantage compared with streptokinase (6.6% v 7.3%, p = 0.02, Bonferroni adjusted p = 0.12, that is borderline significance, relative risk 0.918, 95% confidence interval 0.854 to 0.986). Any benefit is attributable entirely to patients recruited in the United States in the GUSTO I study. There is an increased incidence of stroke with t-PA.

The data do not consistently show a 30 day mortality benefit from using t-PA compared with streptokinase in acute myocardial infarction, but do show increased risk of stroke. Streptokinase can be considered the thrombolytic agent of choice.