Probability of No Urgent Repeated Percutaneous Revascularization Procedures in the Three Treatment Groups (Kaplan-Meier Plots) Figure 1. Probability of No Urgent Repeated Percutaneous Revascularization Procedures in the Three Treatment Groups (Kaplan-Meier Plots). Events began to occur shortly after the index procedure in the placebo group, between 6 and 12 hours after the procedure in the group given the bolus of c7E3 Fab, and even later in the group given both the bolus and the infusion. The y axis is truncated at 97 percent to demonstrate the differences in this end point, which occurred with low frequency. Accessed from: The EPIC Investigators. N Engl J Med 1994;330:956-961

EPIC: Risk of Bleeding with Placebo, Bolus, and Bolus and Infusion Variable Placebo (n=696) C7E3Fab Bolus (n=695) c7E3 Fab Bolus + Infusion (n=708) Major Bleeding – no. (%) 46 (7) 76 (11) 99 (14) Site of Major Bleeding – no. (%) Groin 20 49 58 Need for Surgical Repair 7 (1.0) 16 (2.3) 6 (0.8) Retroperitoneal 3 12 Coronary Artery 23 21 26 Intracranial 2 1 Hematemesis 5 11 Transfusions -- no. (%) Red cells 49 (7) 92 (13) 109 (15) Platelets 18 (3) 29 (4) 39 (6) Accessed from: The EPIC Investigators. N Engl J Med 1994;330:956-961

Reanalysis of EPIC: Early outcomes: Composite rate of death, MI, urgent intervention Time endpoint assessed postrandomization Placebo Bolus P Bolus+ Infusion p vs placebo 6 hour 5.3% 2.9% 0.22 2.4% 0.005 12 hour 6.7% 4.7% 0.129 4.2% 0.047 Marmur JD et al. Am Heart J 2006

EPIC: Heparin Dosing was High Heparin was given intravenously in an initial bolus dose of 10,000 to 12,000 units followed by incremental bolus doses of up to 3000 units at 15-minute intervals, but no more than 20,000 units was given during the procedure; the goal was to keep the activated clotting time between 300 and 350 seconds during the operation. Heparin was continued by constant infusion for at least 12 hours to maintain the activated partial-thromboplastin time at 1.5 to 2.5 times the control value. The EPIC Investigators. N Engl J Med 1994;330:956-961

Limitations of EPIC in the Assessment of Bolus Vs Infusion High doses of heparin cloud assessment of safety Late events after 24 hours in the era of conventional balloon angioplasty may be abrupt closure which has been reduced with the use of stents Clopidogrel loading was not practiced in EPIC Placebo arm in EPIC was UFH and not Enox or Bival Gibson CM, 2006