Randomised, double-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction (INJECT): trial to investigate equivalence. International Joint Efficacy Comparison of Thrombolytics.
Streptokinase and alteplase are established therapies in acute myocardial infarction. Reteplase is a new thrombolytic agent that can be given 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 from 208 centres in nine countries (n = 6010) with symptoms and electrocardiographic criteria consistent with acute myocardial infarction were randomised to receive double-blind either streptokinase 1.5 MU intravenously over 60 min or reteplase two boluses of 10 MU given 30 min apart. Treatment could be started up to 12 h from onset of symptoms. All patients received intravenous heparin for at least 24 h. The primary endpoint was 35-day outcome. There were 270 deaths (9.02%) in the reteplase and 285 deaths (9.53%) in the streptokinase group, a non-significant difference (95% CI -1.98% to 0.96%). Among patients who received treatment (98.8%) there were 263 deaths (8.90%) in the reteplase compared with 279 deaths (9.43%) in the streptokinase group (a difference of -0.53%). Because the upper limit of the 90% CI for this difference is 0.71%, this result shows that reteplase is at least as effective as streptokinase. In-hospital stroke rates were 1.23% for reteplase and 1.00% for streptokinase. Bleeding events were similar in the two treatment groups (0.7% reteplase, 1.0% streptokinase). The incidence of recurrent myocardial infarction was similar, but there were significantly fewer cases of atrial fibrillation, asystole, cardiac shock, heart failure, 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.
D000368:Aged; D002561:Cerebrovascular Disorders / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D010960:Plasminogen Activators / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013300:Streptokinase / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013810:Therapeutic Equivalency; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D006493:Heparin; C087896:reteplase; D013300:Streptokinase; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator