1. Bleeding and Outcomes OASIS Registry, OASIS - 2, CURE (n=34,146) Death
days
bleeding
no bleeding
Bleeding and 30 -
Day Risk*
Event HR
Death
5.37 MI
4.44
Stroke
6.46
30 Day to 6 Month Death
*adjusted with bleeding as time -
dependent covariate, baseline factors,
According to Bleeding
propensity
Eikelboom
Circulation 2006;114: 774 -
782; published online August

2. How Might Bleeding Increase Long - Term Mortality?
Hemodynamic compromise
Hyperadrenergic state
Transfusion – induced microcirculatory disorder, NO depletion, immunologic effects
Inflammatory response
Discontinuation of antithrombotics
Discontinuation of antithrombotics
Discontinuation of antithrombotics

3. CRUSADE Bleeding Risks – Transfusion by Age20
14.9% overall
18.5
17.9
10.3% non -
CABG
14.1 15
10.3
9.7 10
% RBC Transfusion
4.5 5
<65 yrs
65-75 yrs
> 75 yrs
Through Q (n=74,271)
Non-CABG
Overall
Yang, J Am Coll Cardiol 2005;46:1490 - 5

4. Algorithm for Management of NSTE ACS
Likely ACS
Possible ACS
Risk Stratify
High Risk
Indeterminate Risk
ASA 160 -
325mg stat then 81mg daily
ASA 160 -
325mg stat then 81mg daily
Clopidogrel 300mg stat, then 75mg daily
Enoxaparin 1mg/kg bid or Fondaparinux
Fondaparinux 2.5mg sc/day
2.5mg/sc/day for patients with prior cardiac
or Enoxaparin 1mg/kg BID or UFH
history, non CVD or diabetes
Initiate referral to cardiac
catheterisation
lab
Unstable NSTE ACS
Observe 8 -
12 hrs
Eptifibatide or Tirofiban
High Risk
Consider Intra -
aortic balloon pump
Features
Emergency referral to
cath
lab
No High Risk Features
Cardiac catheterization
High Risk
Stress ECG/ Perfusion Scan
in < 48 hours
Features

5. All Types of Bleeding were Reduced in the Fondaparinux Group at Day 9
Outcome
Enoxaparin
(%)
Fondaparinux
P value
No. Randomized
10,021
10,057
Fatal bleeds
0.2
0.1
0.005
TIMI major bleeds
1.3
0.7
<0.001**
Total bleeds (OASIS 5 def’n)
7.3
3.3
<0.001*
Major bleeds
4.1
2.2
<0.001
Minor bleeds
3.2
1.1
*HR (95% Cl): 0.44 ( ); **HR (95* Cl): 0.55 ( )

6. The Reduction in Major Bleeding was
Consistent in Almost All Categories
Major bleeding
at day 9
Enoxaparin
(No. patients)
Fondaparinux
(No. Patients)
P value
No. Randomized
10,021
10,057
Total Major Bleeds
421 (4.1%)
217 (2.2%)
<0.001
Intracranial 7 NS
Requiring surgery to
stop bleeding 77 41
Transfusion
287
164
Retroperitoneal 37 9
Associated with death
at study end 79 38
OASIS 5 Investigators. N Engl J Med 2006; 354:

7. Major Bleeding Lower with Fondaparinux Irrespective of Renal Function
0.10
Enoxaparin
(dose adjusted for renal function)
0.08
Fondaparinux
0.06
Major Bleed
0.04
0.02
0.00 40 60 80
100
120
140
GFR mL/min/1.73m2
Fox KAA. Ann Int Med 2007; 147:

8. The Benefit of Fondaparinux is Consistent Irrespective of the GRACE Risk Score, Supporting its Use in a Broad Range of Patients with NSTEMI
Death, MI and RI at 9 days (%)
Major bleeding at 9 days (%) 12 12
HR 1.17
HR 0.96
HR 0.96
HR 0.42
HR 1.68
HR 0.45 10 10 8
7.5 8
7.2 6
5.2 6
5.3
5.2
5.4
4.5
4.0 4 4
2.7
2.7
2.5 2 2
1.1
<100
>126
<100
>126
Low risk
Intermediate risk
High risk
Low risk
Intermediate risk
High risk
GRACE Score
GRACE Score
Enoxaparin
Fondaparinus
Joyner C. et al. JACC 2006;47(4) Suppl A:abstract

9. A High Proportion of Patients Underwent an Early Invasive Strategy
50.0
8919
Angiography
PCl
40.0
30.0
4254
20.0
3651
2199
10.0
1637
1658
1432
1039
834
723
0.0
<2 hrs
2 – 12 hrs
12 – 24 hrs
24 – 72 hrs
Total < 72 hrs
Time from randomisation
Mehta S. Presented at ESC 2007 Scientific Session Oral Presentation

10. Net Clinical Benefit Favours Fondaparinux
in Patients Undergoing PCl and Early PCl
Outcome Day 9
Enox
N = 3072
Fonda
N = 3105 HR
P value
Death, MI or Stroke
6.2
6.3
1.03
0.79
Major Bleeding
5.1
2.4
0.46
<
Death, MI, Stroke, Major Bleeding
10.4
8.2
0.78
0.004
Early PCl < 24 hours
Death, MI, Stroke
5.4
5.3
0.98
0.89
4.9
2.3
0.48
0.0005
Death, MI Stroke, Major Bleeing
9.5
7.3
0.76
0.005
Mehta SR. JAAC 2007, in press

11. Catheter Thrombus in Both Groups Virtually Eliminated
After Protocal Amendment
No UFH Prior to PCl
UFH Prior to PCl
Enox
(%)
Fonda (%) HR
(95% Cl)
Fonda
No. randomized
810
793 80 75
Death/MI/Stroke
60 (7.4)
57 (7.2)
0.97
( )
5 (6.3)
3 (4.0)
0.62
( )
Major Bleed
35 (4.3)
25 (3.3)
0.75
( )
5 (6.2)
1 (1.3)
0.21
( )
Catheter Thrombus
4 (0.5)
9 (1.1)
2.30
( )
1 (1.3)* -
Final 1758 patients randomized
*represents 1 patient with low dose of UFH 5 units/kg vs. mean dose of 47 units/kg
Mehta SR. JAAC 2007, in press

12. Adding UFH to Fondaparinux for PCl is Safe and Preserves the Lower Bleeding with Fondaparinux versus Enoxaparin
Enox
Fonda HR Cl
No UFH post-randomization
1.2
(n=1277)
0.5
(n=1313)
0.45
UFH or equivalent placebo mandated by protocol during PCl
1.1
(n=1229)
0.4
(n=1279)
0.34
Open label UFH
2.7
(n=598)
1.3
(n=543)
0.48
Overall
1.5
(n=3104)
0.6
(n=3135)
0.42
Mean Dose of UFH for PCI Used in OASIS 5:47 units/kg
Yusuf S. et al. N Engl J Med 2006; 354:2829

13. Fondaparinux Reduces Major Bleeding in
PCl Patients with Both Radial and Femoral Access
Radial
Femoral
9 day events (%)
4.8%
3.5%
2.4%
2.3%
1.6%
0.9%
Overall
Enoxaparin
Fondaparinux
(during blind study drug administration)
Hamon M, Mehta S. et al. AHA Scientific Sessions 2006 Abstract No. 9796