1. Intracoronary Eptifibatide Bolus Administration During Percutaneous Coronary Revascularization for Acute Coronary Syndromes With Evaluation of Platelet Glycoprotein IIb/IIIa Receptor Occupancy and Platelet Function. The Intracoronary Eptifibatide (ICE) Trial Albert J. Deibele MD, Lisa K. Jennings PhD, James E. Tcheng MD, Cathy Neva RN, Angela D. Earhart BS, C. Michael Gibson MS, MD

3. Background Distal embolization of thrombotic debris occurs during PCI for acute coronary syndromes Impaired microvascular perfusion, myonecrosis and increased mortality may result Glycoprotein IIb/IIIa inhibitors have improved outcomes during PCI for acute coronary syndromes by reducing major adverse cardiac events In Vitro studies suggest that very high local concentrations of GP IIb/IIIa inhibitors are effective in disaggregating thrombus

4. Higher levels of GP IIb/IIIa receptor occupancy has led to improved myocardial perfusion in myocardial infarction Intracoronary administration of eptifibatide may result in higher local concentration High local concentration of eptifibatide may lead to increased GP IIb/IIIa receptor occupancy thereby promoting thrombus disaggregation and improved myocardial perfusion Background (cont.)

5. Intracoronary (IC) administration of eptifibatide will result in higher local levels of platelet Glycoprotein IIb/IIIa Receptor Occupancy (RO), reduced thrombus burden and improved measures of coronary flow than intravenous (IV) administration during PCI for acute coronary syndromes. Hypothesis

6. Non ST Elevation Myocardial Infarction Unstable Angina with either ST segment shifts, elevated biomarkers or visible thrombus ST Elevation Myocardial Infarction > 24 hours from treatment with thrombolytics Stenosis > 70% by visual estimate Lesion suitable for coronary stent Informed consent Age > 18 years old Negative pregnancy test for women of child bearing potential Inclusion Criteria

7. Planned PCI within 30 days of index PCI Severe coronary calcification Acute ST elevation Myocardial Infarction Occluded target vessel SVG as the target vessel Left main stenosis > 50% INR > 1.4 Previous stent at the target lesion Contraindication to GP IIb/IIIa Inhibitor therapy DVT Presence of an IVC Filter Exclusion Criteria

8. 43 patients with acute coronary syndromes randomized to IC vs IV bolus of eptifibatide during coronary stenting 2 boluses of 180 mcg/Kg of eptifibatide administered over 2 minutes Second bolus administered 10 minutes after the initial bolus A continuous infusion of eptifibatide 2 mcg/Kg/min started with the initial bolus IC eptifibatide buffered to pH 7.0-7.4 with 2 cc 8% sodium bicarbonate Methods

9. 2 boluses of eptifibatide either administered IC over 2 minutes via guide catheter or over 2 minutes via peripheral IV A Castillo catheter seated in the coronary sinus Coronary sinus samples obtained for GP IIb/IIIa RO during the bolus of eptifibatide – IC at 30 secs and IV at 60 secs Peripheral samples obtained for GP IIb/IIIa RO immediately after the CS sample during the bolus Peripheral studies of the inhibition of platelet aggregation obtained at time 0, 15, 30 and 60 minutes PCI performed after both boluses of eptifibatide were administered Methods (cont.)

11. RESULTS No adverse events occurred during IC administration of eptifibatide No arrhythmias occurred. No occurrences of pericardial effusion, cardiac tamponade or myocardial rupture.

19. IC vs IV administration of eptifibatide results in similar levels of systemic inhibition of platelet aggregation. IC administration of eptifibatide results in higher local levels of GP IIb/IIIa RO. IC treatment with eptifibatide was associated with improved coronary flow and microvascular perfusion by an improved cTFC. Conclusions

20. High first bolus GP IIb/IIIa RO in the coronary sinus was the only factor in a multivariate analysis associated with an improved cTFC. Further prospective, randomized studies to explore the angiographic and clinical efficacy of this strategy are warranted. Conclusions (cont.)

21. This study was supported by a grant from the SMDC Foundation and the University of Tennessee Vascular Biology Center of Excellence SMDC Research Staff Jennifer Gunderson Christine Leone Lezlie Swanson Colleen Renier Jeanette Palcher University of Tennessee Mary Jacoski Angela Earhart Melanie White