AN INTERNATIONAL RANDOMIZED TRIAL COMPARING 4 THROMBOLYTIC STRATEGIESFOR ACUTE MYOCARDIAL-INFARCTION

Background. The relative efficacy of streptokinase and tissue plasmino gen activator and the roles of intravenous as compared with subcutaneo us heparin as adjunctive therapy in acute myocardial infarction are un resolved questions. The current trial was designed to compare new, agg ressive thrombolytic strategies with standard thrombolytic regimens in the treatment of acute myocardial infarction. Our hypothesis was that newer thrombolytic strategies that produce earlier and sustained repe rfusion would improve survival. Methods. In 15 countries and 1081 hosp itals, 41,021 patients with evolving myocardial infarction were random ly assigned to four different thrombolytic strategies, consisting of t he use of streptokinase and subcutaneous heparin, streptokinase and in travenous heparin, accelerated tissue plasminogen activator (t-PA) and intravenous heparin, or a combination of streptokinase plus t-PA with intravenous heparin. (''Accelerated'' refers to the administration of t-PA over a period of 1 1/2 hours - with two thirds of the dose given in the first 30 minutes - rather than the conventional period of 3 ho urs.) The primary end point was 30-day mortality. Results. The mortali ty rates in the four treatment groups were as follows: streptokinase a nd subcutaneous heparin, 7.2 percent; streptokinase and intravenous he parin, 7.4 percent; accelerated t-PA and intravenous heparin, 6.3 perc ent; and the combination of both thrombolytic agents with intravenous heparin, 7.0 percent. This represented a 14 percent reduction (95 perc ent confidence interval, 5.9 to 21.3 percent) in mortality for acceler ated t-PA as compared with the two streptokinase-only strategies (P = 0.001). The rates of hemorrhagic stroke were 0.49 percent, 0.54 percen t, 0.72 percent, and 0.94 percent in the four groups, respectively, wh ich represented a significant excess of hemorrhagic strokes for accele rated t-PA (P = 0.03) and for the combination strategy (P<0.001), as c ompared with streptokinase only. A combined end point of death or disa bling stroke was significantly lower in the accelerated-t-PA group tha n in the streptokinase-only groups (6.9 percent vs. 7.8 percent, P = 0 .006). Conclusions. The findings of this large-scale trial indicate th at accelerated t-PA given with intravenous heparin provides a survival benefit over previous standard thrombolytic regimens.