711-3-A Multicenter, Randomized, Double-Blind Pilot Trial of Standard Versus Low Dose Weight-Adjusted Heparin in Patients Treated with the Platelet GP IIb/IIIa Receptor Antibody c7E3 During Percutaneous Coronary Revascularization

Abstract

Blockade of the platelet GP IIb/IIIa receptor by the monoclonal antibody c7E3 during high-risk coronary intervention reduced the 30-day endpoint of death, MI, or urgent revascularization by 35% in the EPIC trial, but was accompanied by an increase in the rate of major bleeding. In EPIC, heparin was administered as non-weight adjusted bolus doses to a therapeutic activated clotting time (ACT): bleeding increased with maximal in-lab ACT and relative heparin dose. To evaluate the safety and efficacy of weight-adjusted heparin dosing during c7E3 administration (0.25 mg/kg bolus, 10 mcg/min infusion × 12 hrs). 103 pts undergoing coronary intervention were randomized to 1 of 2 regimens of heparin in a blinded fashion: 100 U/kg bolus + additional doses to achieve ACT > 300 sec ( Standard Dose , n = 51), or 70 U/kg bolus without ACT adjustment ( Low Dose , n = 52). ACT values immediately prior to intervention (median and interquartile range) and bleeding complications (unrelated to CABG) during the first 36 hrs (compared to 708 EPIC pts receiving same c7E3 dose). femoral hematoma > 5 cm in size, and in-hospital death or MI were: EPIC Non Wt-Adjusted Standard Wt-Adjusted Low Wt-Adjusted Heparin Heparin Heparin ACT (sec) 398 330 257 (25th, 75th) (356,468) (308,374) (229,288) Major bleeds 7.8% 1.9% 2.0% Minor bleeds 17.9% 7.7% 7.8% Hematoma N/A 15.4% 3.9% Transfusions 15.5% 7.7% 2.0% Thus, reduced weight-adjusted heparin dosing with c7E3 antiplatelet therapy during coronary intervention in this pilot study did not increase ischemic events, and at the same time appeared to decrease bleeding complications. Weight-adjusted heparin strategies will be further tested in a large-scale, randomized trial (EPILOG).