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Can J Cardiol. 1999 Sep;15(9):999-1005.

Evidence-based medicine and reteplase: inductive arguments over deductive reasoning.

[Article in English, French]

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  • 1London Health Sciences Centre, London, Canada.


Two trials of thrombolysis for acute myocardial infarction are contrasted and compared using a systematic approach developed for the interpretation of studies where equivalence is claimed. Reteplase has been compared with streptokinase in a true equivalence trial (International Joint Efficacy Comparison of Thrombolytics [INJECT] trial) and with tissue plasminogen activator in a failed superiority trial (Global Use of Strategies to Open Occluded Coronary Arteries [GUSTO] III). Important methodological distinctions and economic insights are highlighted. Using this approach one can conclude that the INJECT investigators have shown that reteplase is at least as effective as streptokinase and that the test for equivalence was satisfied. The point estimate of the treatment effect for the primary outcome event favours reteplase over streptokinase, and the confidence intervals essentially eliminate the possibility of streptokinase superiority. The GUSTO III primary outcome event, 30-day mortality, provides no convincing evidence that reteplase is equivalent to tissue plasminogen activator. Selective emphasis on one or two post hoc outcome event clusters, such as death and nonfatal stroke, or death and disabling stroke, provides some suggestive, but not conclusive, evidence for equivalence. Moreover, for some of the outcome events, and in particular the primary outcome event, the point estimate suggests that reteplase is, in fact, slightly less effective than tissue plasminogen activator.

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