Holding GUSTO up to the light. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, a recent randomized "megatrial" of thrombolytic therapies in acute myocardial infarction, showed a statistically significant decrease of 30-day mortality in patients treated with accelerated-dose tissue plasminogen activator (tPA) compared with streptokinase. The therapeutic and cost implications of the results have been intensely scrutinized, and several commentaries have been written on the interpretation of the study. Questions have been raised about the treatment benefit in certain subgroups, the validity of the results because of the open-label design, the relevance of a 1% absolute benefit in mortality rates, the cost-effectiveness of the drug, and the generalizability of the results. These issues are all important considerations for translating the results of this study into clinical practice worldwide. This article sheds additional light on the interpretation of GUSTO, clarifies misconceptions that may have clouded understanding of the trial results, and discusses the contributions of this trial in advancing our understanding of modern myocardial reperfusion therapy.