Acute myocardial infarction: thrombolysis.

nfarction is the most intensively studied medical intervention in the history of clinical investigation, with more than 200 000 patients enrolled in large scale, worldwide trials. The results of these trials have led to an irrevocably altered approach, with routine use of reperfusion treatment. Streptokinase, tissue plasminogen activator (t-PA), and new plas-minogen activators have been shown to reduce mortality significantly, and the reduction is inversely proportional to the time that treatment is initiated from symptom onset. For patients treated in the first 60 minutes of symptom onset, the so called " golden hour " , mortality is reduced by more than 50%. Even frank prevention of the event can be assured in many patients treated in this very early time frame. Nevertheless, there are some major obstacles to optimal reperfusion treatment that have been increasingly recognised in recent years, which new directions in this field will hopefully circumvent. This paper will review the substantive progress in the field, including recognition of major pitfalls, and lay the groundwork for future improvements in phar-macologic myocardial reperfusion treatment. " Patency centric " approaches With the validation of intravenous thrombo-lytic treatment versus placebo in the classic GISSI 1 and ISIS 2 trials, 1 2 the next step was to determine whether a higher level of early infarct vessel patency would result in improved survival. This was the focus of the GUSTO 1 trial which showed that a significant increase in patency at 90 minutes after treatment was initiated , from 30% with streptokinase to 54% with accelerated t-PA, was associated with a 15% reduction in mortality (fig 1). 3 The term " patency " refers to brisk flow and clearance of angiographic contrast dye through the aVected epicardial artery. More recently, trials of new plasminogen activators have gone forward using accelerated t-PA as the " gold " standard for comparison. The new plasminogen activators are bioengi-neered mutants of wild type t-PA. All have longer half lives and are administered as a single or double bolus. Three new agents, reteplase (r-PA), tenectaplase (TNK), and lan-etoplase (n-PA) have each been studied in trials of 15 000 to 17 000 patients. None of these trials have shown superior mortality outcomes with the new plasminogen activators compared with t-PA. For TNK, " equivalence " was demonstrated with virtually the same mortality for TNK as with t-PA, 2 but for r-PA and n-PA there were very small gaps in …