Abciximab facilitates the rate and extent of thrombolysis - Results of thethrombolysis in myocardial infarction (TIMI) 14 trial

Background-The TIMI 14 trial tested the hypothesis that abciximab, the Fab fragment of a monoclonal antibody directed to the platelet glycoprotein (GP ) IIb/IIIa receptor, is a potent and safe addition to reduced-dose thrombol ytic regimens for ST-segment elevation MI. Methods and Results - Patients (n=888) with ST-elevation MI presenting <12 hours from onset of symptoms were treated with aspirin and randomized initi ally to either 100 mg of accelerated-dose alteplase (control) or abciximab (bolus 0.25 mg/kg and 12-hour infusion of 0.125 mu g . kg(-1) . min(-1)) al one or in combination with reduced doses of alteplase (20 to 65 mg) or stre ptokinase (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 th ose treated with a regimen including abciximab received low-dose heparin (6 0-U/kg bolus; infusion of 7 U . k(-1) . h(-1)) The rate of TIMI 3 flow at 9 0 minutes for patients treated with accelerated alteplase alone was 57% com pared with 32% for abciximab alone and 34% to 46% for doses of streptokinas e 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 admini stration of alteplase, progressing from a bolus alone to a bolus followed b y either a 30- or 60-minute infusion (P<0.02), The most promising regimen w as 50 mg of alteplase (15-mg bolus; infusion of 35 mg over 60 minutes), whi ch produced a 76% rate of TIMI 3 flow at 90 minutes and was tested subseque ntly in conjunction with either low-dose or very-low-dose (30-U/kg bolus; i nfusion of 4 U . kg(-1) h(-1)) heparin, TIMI 3 flow rates were significantl y higher in the 50-mg alteplase plus abciximab group versus the alteplase-o nly group at both 60 minutes (72% versus 43%; P = 0.0009) and 90 minutes (7 7% versus 62%; P=0.02), The rates of major hemorrhage were 6% in patients r eceiving alteplase alone (n = 235), 3% with abciximab alone (n = 32), 10% w ith 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 p lus abciximab with very-low-dose heparin (n = 70), Conclusions-Abciximab facilitates the rate and extent of thrombolysis, prod ucing early, marked increases in TIMI 3 flow when combined with half the us ual dose of alteplase. This improvement in reperfusion with alteplase occur red without an increase in the risk of major bleeding. Substantial reductio ns in heparin dosing may reduce the risk of bleeding even further. Modest i mprovements in TIMI 3 flow were seen when abciximab was combined with strep tokinase, but there was an increased risk of bleeding.