Thrombolytic Therapy for Acute Myocardial Infarction: GUSTO Criticized

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Abstract
After an intensive marketing campaign by Genentech, the report by the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) investigators (Sept. 2 issue)1 has finally appeared. In view of the small survival advantage conferred by tissue plasminogen activator (t-PA) (0.9 percent -- an effect evident only when it is administered within four hours after the onset of symptoms), the increased risk of stroke, and the striking difference in the expense of therapy (a difference of $220,000 to save a single life: $2,300 - $320 × 100 divided by 0.9), the fact that t-PA is the most frequently used thrombolytic agent in the United States is indeed puzzling. Sharp differences in patient grouping and the lack of a consistent number of patients in the groups render the statistical differences suspect. The conclusions about the effects of treatment according to age are also of concern: the 0.9 percent increase in the incidence of hemorrhagic stroke observed with t-PA in patients older than 75 years had no effect on the resulting differences in the outcomes of death or nonfatal disabling stroke, whereas in patients ≤ 75 years a 0.1 percent increase in this complication resulted in a 0.1 percent reduction in the combined outcome. The occurrence of revascularization in 24 percent of the patients may be an important confounder; however, the distribution of revascularization according to groups has been pointedly omitted: in fact, 0.5 percent more patients had coronary angioplasty and 0.8 percent more had coronary-bypass surgery in the t-PA group than in the two streptokinase groups combined. Also, even though more than 75 percent of the study group received thrombolytic therapy within four hours of the onset of symptoms, the median time for a patient with an acute myocardial infarction to arrive at a treatment facility exceeds the length of time in which treatment can confer a possible advantage. Indeed, if t-PA was the only drug used to treat myocardial infarction, it might result in no overall benefit and possibly in a worsening of outcome.