Trial of abciximab with and without low-dose reteplase for acute myocardial infarction. Strategies for Patency Enhancement in the Emergency Department (SPEED) Group.
BACKGROUND
Low-dose alteplase with standard-dose abciximab enhances reperfusion 90 minutes after acute myocardial infarction (MI). We combined standard-dose abciximab with low-dose reteplase for acute MI in 2 phases. Two heparin doses were also explored.


RESULTS
Phase A patients were randomized 4:1 to receive an abciximab bolus with infusion alone (n=63) or with 5 U, 7.5 U, 10 U, 5 U+2.5 U, or 5 U+5 U of reteplase (total n=241). Phase B tested the best phase A strategy (abciximab plus 5 U+5 U reteplase, expressed as abciximab-reteplase 5+5 U; n=115) against 10 U+10 U reteplase alone (n=109). The primary end point was Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow at 60 to 90 minutes. In phase A, 62% of the abciximab-reteplase 5+5 U group had TIMI grade 3 flow versus 27% of the abciximab-only patients (P=0.001). In phase B, 54% of the abciximab-reteplase 5+5 U group had grade 3 flow versus 47% of the reteplase-only patients (P=0.32). Grade 3 flow rates were 61% for a 60 U/kg heparin bolus and abciximab-reteplase 5+5 U, 51% for a 40 U/kg heparin bolus and abciximab-reteplase 5+5 U (P=0.22), and 47% for reteplase alone (P=0.05 versus the 60 U/kg heparin group). Major bleeding rates in phase A were 3.3% for abciximab alone and 5.3% for abciximab-reteplase 5+5 U; rates in phase B were 9.8% for abciximab-reteplase 5+5 U and 3.7% for reteplase alone. Major bleeding was similar with standard- or low-dose heparin (6.3% versus 10.5%, P=0.30).


CONCLUSIONS
In this phase II trial, adding reteplase to abciximab treatment of acute MI versus reteplase alone enhanced the incidence of early complete reperfusion after the initiation of therapy in the emergency department.
D000077284:Abciximab; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001803:Blood Transfusion; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced / Q000628:therapy; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D015425:Myocardial Reperfusion / Q000379:methods; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D011994:Recombinant Proteins; C087896:reteplase; D010959:Tissue Plasminogen Activator; D000077284:Abciximab