Secondary Efficacy Endpoints

Secondary Efficacy Endpoints • Secondary Efficacy Endpoints: • Frequency/extent of myonecrosis post-PCI • Assessed with serial CK-MB, cTnI/T • Total duration of ischemia post-PCI • Continuous ST-segment monitoring for 24 hours • Criterion: 1mm of ST-deviation for at least one minute • Composite of death/MI or Holter ischemia within 48 hours

Other Efficacy Endpoints • Inflammatory response post-PCI: Peak rise* in sCD40L Peak rise* hsCRP • Thrombin generation post-PCI Peak rise* in F 1.2 * Peak rise is defined as the rise in the biomarker from baseline to its peak value by 24 hours (-6 / +12 hours) post-PCI based on Core Laboratory analysis.

Primary Safety Endpoint • Primary Safety Endpoint: • TIMI Major Hemorrhage Adjudicated by CEC • Either of the following: • (1) Intracranial or • (2) Hemorrhage (including via imaging study) that is associated with a fall in hemoglobin of >5 g/dL (or, when hemoglobin is not available, a fall in hematocrit of >15%) • Transfusion adjusted for (1 unit = 1g/dl)

Baseline Characteristics EPT BIV P-value n = 573 n = 284 Age (yrs) 60.0 ± 11.1 59.7 ± 9.8 NS

Presenting Characteristics EPT BIV P-value n = 573 n = 284 NS NS NS NS 43.8 NS 44.2 NS 56.2 55.8

Primary Endpoint: Coronary Flow Reserve CFR Post Adenosine CTFC p = 0.036 open arteries p = 0.13 all pts p=NS Coronary Flow Reserve Corrected TIMI Frame Count N=516 N=238 N=501 N=232

Change in TIMI Frame Count After PCI vs After Adenosine Values expressed as a median.

Eptifibatide Bivalirudin (Post PCI) 45 MPH 42 MPH Speeds up by a factor of 1.33 Speeds up by a factor of 1.43 (Adenosine) (Post Adenosine) 60 MPH 60 MPH

TIMI Myocardial Perfusion Grade 3 Post-PCI O.R. 1.44 (95% CI 1.003-2.06) p = 0.048 pre-specified adjustment for baseline TMPG Post-PCI TMPG 3 N=506 N=232

Duration of Ischemia on Holter Monitoring through 24 Hours Post-PCI Duration of Ischemia in Patients with an Event Ischemic Event by 24 hours p=NS p=0.013 % Median Duration (minutes) N=525 N=265 N=28 N=15

Death, MI or Ischemia on Holter Monitoring through 48 Hours O.R. 1.38 (95% CI 0.93-2.06) for Death/MI/Ischemia (p=0.11) O.R. 1.45 (95% CI 0.85-2.46) for Death/MI (6.3% vs 8.8%) 18.0% 13.8% Ischemia 11.6% % Ischemia 8.7% D / MI 8.8% MI 8.5% D / MI 6.3% MI 6.3% Death 0.4% Death 0% N=267 N=530

Peak Rise in Troponin I Post-PCI p=0.147 Median troponin I (ng/ml) N=498 N=255

TIMI Major & Minor Hemorrhage within 48 Hours TIMI Major Hemorrhage EPT + ENOX vs BIV: p = 0.053 p=0.308 % TIMI Minor Hemorrhage EPT + ENOX vs BIV: p=0.201 EPT + UFH vs BIV: p=0.021 p=0.027 %

Transfusions within 48 Hours EPT + ENOX vs BIV: p = 0.001 EPT + UFH vs BIV: p = 0.003 p<0.001 %

PROTECT Trial: Summary • The primary endpoint, the improvement in flow after adenosine or coronary flow reserve, was significantly greater for bivalirudin in open arteries, but when abrupt closure/bail out was adjusted for as pre-specified, the strategies were similar • Final post adenosine CTFC (flow) was identical in the two arms • Post-PCI myocardial perfusion was significantly improved by Eptifibatide • Ischemia duration on the post-PCI Holter was significantly shorter with Eptifibatide • Death / MI trended to be lower for Eptifibatide • Peak rise in Tn trended to be lower for Eptifibatide • The primary safety endpoint, TIMI major bleeding did not differ between strategies, TIMI minor bleeding and transfusion was significantly less with bivalirudin

PROTECT Trial: Conclusions Compared with Bivalirudin, Eptifibatide significantly improved myocardial perfusion and significantly reduced the duration of post-PCI ischemia; it also directionally reduced clinical events and myonecrosis, but these benefits came at the expense of an increase in non-fatal bleeding

Myocardial Infarction - Major Bleeding: Net Clinical Benefit Favors GP IIbIIIa / Eptifibatide Favors Bivalirudin 0.8 0.3 ∆ Major Bleeding ∆ MI REPLACE 2: 0.5 Net Benefit 0.7 2.2 ∆ Major Bleeding ∆ MI PROTECT: 1.5 40% DM, > 50% Tn+ Net Benefit Event Rate (%)

Secondary Efficacy Endpoints