Abstract :
Background
Plasminogen activator therapy for acute myocardial infarction is limited by lack of achievement of early, complete, and sustained reperfusion in a substantial proportion of patients. Many phase II trials have supported the potential of combined fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition for improving reperfusion. We did a randomised, open-label trial to compare the effect of reteplase alone with reteplase plus abciximab in patients with acute myocardial infarction.
Methods
16 588 patients in the first 6 h of evolving ST-segment elevation myocardial infarction were randomly assigned standard-dose reteplase (n=8260) or half-dose reteplase and full-dose abciximab (n=8328). The primary endpoint was 30-day mortality, and secondary endpoints included various complications of myocardial infarction. Analysis was by intention to treat.
Findings
At 30 days, 488 (5·9%) of patients in the reteplase group had died, compared with 468 (5·6%) in the combined reteplase and abciximab group (odds ratio 0·95 [95% CI 0·83–1·08], p=0·43). There were fewer deaths or non-fatal reinfarctions with the combination than with reteplase alone, and there was less need for urgent revascularisation and fewer major non-fatal ischaemic complications of acute myocardial infarction. On the other hand, there were more non-intracranial bleeding complications in the combination group. The rates of intracranial haemorrhage and non-fatal disabling stroke were similar.
Interpretation
Although combined reteplase and abciximab was not superior to standard reteplase, the 0·3% absolute (5% relative) decrease in 30-day mortality fulfilled the criteria of non-inferiority. Combination therapy led to a consistent reduction in key secondary complications of myocardial infarction including reinfarction, which was partly counterbalanced by increased non-intracranial bleeding complications.
