RANDOMIZED, DOUBLE-BLIND COMPARISON OF RETEPLASE DOUBLE-BOLUS ADMINISTRATION WITH STREPTOKINASE IN ACUTE MYOCARDIAL-INFARCTION (INJECT) - TRIAL TO INVESTIGATE EQUIVALENCE

Streptokinase and alteplase are established therapies in acute myocard ial infarction. Reteplase is a new thrombolytic agent that can be give n as a double bolus. This trial was designed to determine whether the effect of reteplase on survival was at least equivalent (within 1% of fatality rate) to that of a standard streptokinase regimen. Patients f rom 208 centres in nine countries (n=6010) with symptoms and electroca rdiographic criteria consistent with acute myocardial infarction were randomised to receive double-blind either streptokinase 1.5 MU intrave nously over 60 min or reteplase two boluses of 10 MU given 30 min apar t. Treatment could be started up to 12 h from onset of symptoms. All p atients received intravenous heparin for at least 24 h. The primary en dpoint was 35-day outcome. There were 270 deaths (9.02%) in the retepl ase and 285 deaths (9.53%) in the streptokinase group, a non-significa nt difference (95% Cl -1.98% to 0.96%). Among patients who received tr eatment (98.8%) there were 263 deaths (8.90%) in the reteplase compare d with 279 deaths (9.43%) in the streptokinase group (a difference of -0.53%). Because the upper limit of the 90% Cl for this difference is 0.71%, this result shows that reteplase is at least as effective as st reptokinase. In-hospital stroke rates were 1.23% for reteplase and 1.0 0% for streptokinase. Bleeding events were similar in the two treatmen t groups (0.7% reteplase, 1.0% streptokinase). The incidence of recurr ent myocardial infarction was similar, but there were significantly fe wer cases of atrial fibrillation, asystole, cardiac shock, heart failu re, and hypotension in the reteplase group. We conclude that reteplase is an effective drug in the treatment of acute myocardial infarction. It is clinically safe, its administration is simple, and it will be a useful addition to the range of thrombolytic agents available.