1. 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

2. 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.

3. 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)

4. Baseline Characteristics
EPT BIV P-value
n = n = 284
Age (yrs) ± ± NS
Male (%) 66 68 NS
Prior MI (%) 22 20
Prior PCI (%) 25 24
Prior CABG (%) 7
Prior CHF (%) 5 6
Hypertension (%) 65
Cigarette Smoker (%) 38 36
Diabetes (%) 44
0.026
Dyslipidemia (%) 54 56
Mike, Since we present data from all 3 arms, shouldn’t we present the demographics from all three groups rather than just the two?
I enlarged title font

5. Presenting Characteristics
EPT BIV P-value
n = n = 284
ST Depression
30.8
27.5
Elevated Troponin I (%)
52.4
54.8
Elevated Troponin I > 10X ULN (%)
30.2
26.2
Elevated CK-MB (%)
20.1
18.3
Pre-PCI TMPG 0/1/2
Pre-PCI TMPG 3 NS NS NS NS
43.8
44.2 NS
56.2
55.8 NS

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

7. Change in TIMI Frame Count After PCI vs After Adenosine
Eptifibatide
Bivalirudin
p - value
Pre-PCI CTFC 32
30.6 NS
Post-PCI CTFC 19 21
0.16
Favors Eptifibatide
Improvement in CTFC following PCI (Post PCI – Pre PCI, or delta in CTFC from pre to post PCI) 10 8
0.10
Post-Adeno CTFC 14
Improvement in CTFC following Adenosine (Post adenosine – Post PCI)
4.7 6
0.12
Favors Bival
CFR Based Upon Improvement in CTFC After Adenosine
(Post-PCI CTFC ÷ Post-Adeno CTFC)
1.33
1.43
0.036
P-value After Pre-Specified Adjustment for Abrupt Closure and Thrombotic Bail Out
0.13
Values expressed as a median.

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

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

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

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

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

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

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

15. 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

16. 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

17. Myocardial Infarction - Major Bleeding: Net Clinical Benefit
Favors Bivalirudin
Favors GP IIbIIIa / Eptifibatide
0.3
0.8
∆ 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 (%)