Heart Care Centers of Illinois

Design –Single arm, open label, 13 U.S. centers –Patients with ST-segment elevation myocardial infarction (STEMI) Less than 12 hours duration No prior thrombolytic therapy Primary PCI required –Patient population matched to CADILLAC by inclusion and exclusion criteria –Comparable efficacy endpoints

Design (cont.) –Treatment: Bivalirudin 0.75mg/kg bolus, 1.75mg/kg/hr infusion for duration of procedure –Optional post-procedure infusion: 0.25mg/kg/hr –Abciximab if TIMI flow <3 at end of procedure –Primary endpoints of safety and efficacy evaluated at 7 days/hospital discharge, 30 days and 6 months

Inclusion Criteria –Symptoms of STEMI for at least 30 min within previous 12 hours AND ST-segment elevation in at least 2 contiguous leads or new LBBB or existing LBBB with positive troponin Residual high grade stenosis and associated abnormalities in regional wall motion. –Planned primary PCI in native coronary vessel

Exclusion Criteria –Prior LMWH, Thrombolytics, GP IIb/IIIa inhibitors –Cardiogenic shock (SBP 30 min or a need for intravenous pressors) –Stroke or neurosurgery within 3 months –Severe hypertension not adequately controlled by antihypertensive therapy at the time of study entry (BP >180/110 mm Hg) –Life expectancy <1 year –Heparin only therapy allowed prior to PCI 30 minute washout, or ACT <250

Primary Endpoints –Efficacy Evaluated at 7 days/hospital discharge, at 30 days, and 6 months composite and individual components of: Death (cardiac and unknown cause) Reinfarction Repeat intervention/revascularization of target lesion as a result of ischemia Disabling stroke Rate of subacute thrombosis at 7 days/hospital discharge and at 30 days

Primary Endpoints –Safety Evaluated at 7 days/hospital discharge: Clinically significant bleeding defined as: –Intracranial, retroperitoneal, or ocular bleeding –Access site hemorrhage requiring surgical intervention or a >5cm diameter hematoma –Reduction in Hgb concentration of >3g/dL with overt bleeding –Any blood transfusion –Any reoperation for bleeding Thrombocytopenia ( 50% from baseline)

BIAMI Sites Joseph StellaHeart Care Centers of Illinois / Heart Care Research Foundation at St. Francis Hospital and MacNeal Hospital Jay GanjiMoses Cone Memorial Hospital LeBauer Cardiovascular Research Foundation Garry MacKenzieMcKay-Dee Hospital Center John McKnightMonongalia General Hospital Kevin BrowneLakeland Regional Medical Center Watson Clinic Center for Research Anil Sahijwani & Monica ValGarijo University Community Hospital Pepin Heart & Vascular Institute Abnash JainWest Virginia University Hospital Ron WaksmanCardiovascular Research Institute Washington Hospital Center Michael AttubatoNew York University Medical Center Ali Rizvi & Matthew French The Care Group at The Heart Center of Indiana and St Vincent Hospital of Indianapolis J. Kern BucknerSouth Denver Cardiology Associates Robert ApplegateWake Forest Baptist Medical Center

Patients Enrolled 201 Safety day day patients lost to f/u ITT 201 PCI unsuccessful 3 PCI successful 194 Cath Only 4 Enrollment and Follow-up 6-month patients lost to f/u Ed. 4/19

CADILLAC Comparison with CADILLAC entry criteria and efficacy prespecified in protocol CADILLAC, 2082 AMI patients, 2x2 factorial design (PTCA or stent with and without abciximab) Abciximab/stent group (n=524) used as comparison –Highest % TIMI 3 flow rate end of procedure –Lowest composite endpoint at 30 days and 6 months G. Stone M.D., C. Grines M.D., D. Cox M.D. N Engl J Med, Vol. 346, No. 13 March 28, 2002

Patient Characteristics BIAMI (N=201) Abciximab/Stent (N=524) Age, yr 6059 Weight, Kg Male sex, % Diabetes mellitus, % Current smoking, % Prior infarction, % Prior percutaneous intervention, % Prior bypass surgery, % Prior stroke or transient ischemic attack, % Left ventricular ejection fraction, Median CADILLAC Comparison

Target Vessel/ Lesion Characteristics BIAMI (N=197) Abciximab/ Stent (N=524) Infarct Vessel % Left anterior descending coronary artery Left circumflex artery Right coronary artery Target Lesion % A B1 B2 C VISIBLE THROMBUS na Ed 5/9

PCI Therapy Stents n –Drug Eluting Stents 123 –Cypher 69 –Taxus 64 –Bare Metal Stents54 –Drug Eluting and Bare Metal10 –Thrombectomy 16

Anticoagulation –All patients received bivalirudin during their PCI 60% of patients received UFH before their intervention 40% of patients received NO UFH, only bivalirudin NO significant bleeding occurred in the patient population that received BOTH UFH and bivalirudin Mean ACT 189 seconds in patients who received UFH.

Concomitant Meds Clopidogrel % Prior to Enrollment12.4 Prior to PCI After PCI

Concomitant Meds Abciximab bolus and infusion –Administration for less than TIMI-3 flow post procedure –TIMI-3 flow achieved post-Abcixmab n/N 20/197 12/20 %

Of the 194 patients with a successful PCI, 86 required post-procedure anticoagulation: Angiomax ® 64 patients Heparin 14 patients Both 8 patients

Post Procedure Heparin (non CABG) Heparin (N=22) Unfractionated heparin IABP Low molecular weight heparin5 Reasons for heparin continuation IABP Transition to Warfarin DVT / PE prophylaxis Other

Post Procedure Angiomax ® (non CABG) * Only 25 patients had greater than 30 minutes Angiomax Angiomax (N=72*) Dose0.25 mg/kg/hr Duration, median4 hrs

Pre/Post-Procedure TIMI Flow Pre-TIMI Flow (N=197) % Post-TIMI Flow (N=197) % TIMI TIMI TIMI TIMI * Visible Thrombus present prior to procedure in 61.2% of patients. Ed 4/21

Primary Endpoint Efficacy 7-Day (N=201) % 30-Day (N=196) % 6-Month (N=190) % Ischemic Composite Death Reinfarction Ischemic TLR Stroke* Subacute Thrombosis**1.0 * Both strokes post CABG ** SAT not collected to 6 months Ed. 5/9

Efficacy 30 days: Patient Details Endpoint Revasc Proc/ Days post primary PCI Age DM Pre Clop Concomitant Meds Infarct lesion stent Narrative Reinfarction Revascularization Subacute Thrombosis #01005 PCI 5 days 60 yr Female No Heparin For IABP post primary procedure BMS (2.0 x 13mm) Experienced chest pain 5 days post PCI Heparin post procedure for IABP No abciximab. Angiography revealed SAT to previously placed stent in LAD. Repeat stent LAD/RCA. Revascularization Death #14004 PCI 1 day 83 yr Female No Angiomax (low dose 4 hrs) Post primary procedure 4 stents in index vessel 2 BMS 2 Cypher Staged procedure. Post PCI. 3VD, BMS & Cypher (4 stents) in LAD. Next day PTCA in LAD, stents in RCA. Acute anterior wall MI with 3VD PCI of all 3 vessels Death secondary to CHF Revascularization #07004 CABG 19 days 72 yr Male No Abciximab IC – NTG Cypher (3.0 x 28) (2.5 x 18) Ant-LAT MI Cypher 2 LAD/DIAG Recath next day Residual disease LAD/Ischemia 19 days later - CABG 03/23

Efficacy 30 days: Patient Details contd. Endpoint Revasc Proc/ Days post primary PCI Age DM Pre Clop Concomitant Meds Infarct lesion stent Narrative Revascularization Stroke #1011 CABG 22 days 66 yr Female No -BMS (3.0 x 24) No post procedure anticoag Presented with ischemia Stroke #10003 CABG 2 days 63 yr Male YesNo-Taxus (3.0 x 20) Heparin for CABG and 15 days for ventrical apical thrombus Subacute Thrombosis #2013 Planned PCI 2 days 70 yr Male NoYes-Taxus (3.5 x 24) Finding of SAT in primary lesion when undergoing PCI for 2 nd lesion in staged procedure 03/23

Deaths at 30 days : Patient Details Endpoint Days post primary PCI Age DM Pre Clop Concomitant Meds Infarct lesion stent Narrative Cardiac Death 2 days89 yr Female No Angiomax for 6 hrs 1 Cypher 3.0 x 13mm LAD Death – arrest 2 nd day post procedure 3 VD Cardiac Death 2 days77 yr Female Yes AbciximabCypherDiabetic. Remained hypotensive post procedure Death – multisystem organ failure. Non Cardiac Death 26 days78 yr Female No -2 BMS 3x13 3.5x 3.5 COPD, hypertension. Anemia prior to index procedure. 2VD Readmitted with lower GI bleeding. Death – cardiac arrest. Cardiac Death 30 days83 yr Female No Angiomax continued Low dose MultipleAnterior wall MI 3 VD. Two procedures, stents in all 3 vessels. Death – complications of CHF.

Bleeding Endpoint –All bleeds had post procedural anticoagulation Safety 7-Day (N=201) % Clinically Significant Bleed3.0 Blood Product Transfusion2.5 Intracranial Hemorrhage0.0 Thrombocytopenia1.5 i. Abciximab & IABP #9002 ii. IABP Bleed #12005 ii. No PCI / on table arrest #6003 Ed 5/9

Clinically Significant Bleeding : Details AgeGenderSiteTx Hgb g/dL Decrease Clopidogrel PriorPost Procedure Meds 85 #07011 FemaleGroin hematomaYesNoYesAbciximab 78 #14013 FemaleNone identifiedYes3.3NoAngiomax 4.2 hrs. 79 #14012 FemaleNone identifiedYes YesAngiomax 4 hrs, no PCI Delayed PCI with Heparin Heparin continued 7 hrs post PCI Transfusion post PCI 82 #07002 FemaleNone identifiedYes1.8NoAngiomax 4 hrs post index for persistent thrombus 64 #14018 FemalePseudoaneurysmNo5.0YesAngiomax 4 hrs post index procedure 45 #1046 FemaleRetroperitonealYes4.7NoHeparin post procedure All bleeds had post procedural anticoagulation/antiplatelet Ed 04/21

30-Day Clinical Outcomes Comparison to CADILLAC BIAMI (N=196) Abciximab/Stent (N=524) 30-Days % Ischemic Composite Death Reinfarction Ischemic TLR Disabling Stroke * * Two Strokes Post CABG Ed. 5/9

6-Month Clinical Outcomes Comparison to CADILLAC BIAMI (N=190) Abciximab/Stent (N=524) 6-Months % Ischemic Composite Death Reinfarction Ischemic TLR Disabling Stroke* * Two Strokes Post CABG Ed. 4/18