E J Topol1. 1. Desk F25, Cleveland Clinic Foundation, 9500 Euclid Avenue, 44195, Cleveland, OH, USA. topole@ccf.org
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:16588 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.
RCT Entities:
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: 16588 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.
Authors: Ulf Bertram; Martin Moser; Karlheinz Peter; Helmut F Kuecherer; Raffi Bekeredjian; Andreas Straub; Thomas K Nordt; Christoph Bode; Johannes Ruef Journal: J Thromb Thrombolysis Date: 2002-12 Impact factor: 2.300