Patients (n=888) with ST-elevation MI presenting <12 hours from onset of symptoms were treated with
aspirin and randomized initially to either 100 mg of accelerated-dose
alteplase (control) or
abciximab (bolus 0.25 mg/kg and 12-hour infusion of 0.125 microg. kg-1. min-1) alone or in combination with reduced doses of
alteplase (20 to 65 mg) or
streptokinase (500 000 U to 1.5 MU). Control patients received standard weight-adjusted
heparin (70-U/kg bolus; infusion of 15 U. kg-1. h-1), whereas those treated with a regimen including
abciximab received low-dose
heparin (60-U/kg bolus; infusion of 7 U. kg-1. h-1). The rate of TIMI 3 flow at 90 minutes for patients treated with accelerated
alteplase alone was 57% compared with 32% for
abciximab alone and 34% to 46% for doses of
streptokinase between 500 000 U and 1.25 MU with
abciximab. Higher rates of TIMI 3 flow at both 60 and 90 minutes were observed with increasing duration of administration of
alteplase, progressing from a bolus alone to a bolus followed by either a 30- or 60-minute infusion (P<0.02). The most promising regimen was 50 mg of
alteplase (15-mg bolus; infusion of 35 mg over 60 minutes), which produced a 76% rate of TIMI 3 flow at 90 minutes and was tested subsequently in conjunction with either low-dose or very-low-dose (30-U/kg bolus; infusion of 4 U. kg-1. h-1)
heparin. TIMI 3 flow rates were significantly higher in the 50-mg
alteplase plus
abciximab group versus the
alteplase-only group at both 60 minutes (72% versus 43%; P=0.0009) and 90 minutes (77% versus 62%; P=0.02). The rates of major
hemorrhage were 6% in patients receiving
alteplase alone (n=235), 3% with
abciximab alone (n=32), 10% with
streptokinase plus
abciximab (n=143), 7% with 50 mg of
alteplase plus
abciximab and low-dose
heparin (n=103), and 1% with 50 mg of
alteplase plus
abciximab with very-low-dose
heparin (n=70).
CONCLUSIONS:
Abciximab facilitates the rate and extent of thrombolysis, producing early, marked increases in TIMI 3 flow when combined with half the usual dose of
alteplase. This improvement in reperfusion with
alteplase occurred without an increase in the risk of major
bleeding. Substantial reductions in
heparin dosing may reduce the risk of
bleeding even further. Modest improvements in TIMI 3 flow were seen when
abciximab was combined with
streptokinase, but there was an increased risk of
bleeding.