Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial.
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.


RESULTS
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.


CONCLUSIONS
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.
Topol
E J
EJ
Desk F25, Cleveland Clinic Foundation, 9500 Euclid Avenue, 44195, Cleveland, OH, USA. topole@ccf.org
D000077284:Abciximab; D000284:Administration, Oral; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D015425:Myocardial Reperfusion; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D015996:Survival Rate; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; C087896:reteplase; D010959:Tissue Plasminogen Activator; D001241:Aspirin; D000077284:Abciximab