30 day to 6 month death
DESCRIPTION
-. 2, CURE (n=34,146). OASIS Registry, OASIS. bleeding. Death. no bleeding. days. Bleeding and Outcomes. 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. -. According to Bleeding. - PowerPoint PPT PresentationTRANSCRIPT
30 Day to 6 Month Death
According to Bleeding
Bleeding and 30 - Day Risk*
Event HR
Death 5.37
MI 4.44
Stroke 6.46
Eikelboom Circulation 2006;114: 774 - 782; published online August 14 2006
Dea
th
days
bleeding
no bleeding
*adjusted with bleeding as time -dependent covariate, baseline factors, propensity
Bleeding and Outcomes
OASIS Registry, OASIS - 2, CURE (n=34,146)
How Might Bleeding Increase Long -Term Mortality?
•Hemodynamic compromise
•Hyperadrenergic state
•Transfusion – induced microcirculatory disorder, NO depletion, immunologic effects
•Inflammatory response
•Discontinuation of antithrombotics
Through Q2 2004 (n=74,271)
CRUSADE Bleeding Risks – Transfusion by Age
4.5
10.3
14.1
9.7
17.9 18.5
0
5
10
15
20
<65 yrs 65-75 yrs > 75 yrs
% R
BC
Tra
nsf
usi
on
Non-CABG Overall
Yang, J Am Coll Cardiol 2005;46:1490-5
14.9% overall10.3% non -CABG
Algorithm for Management of NSTE ACS
Likely ACS Possible ACS
Risk Stratify
High Risk Indeterminate Risk
ASA 160-325mg stat then 81mg dailyClopidogrel 300mg stat, then 75mg dailyFondaparinux 2.5mg sc/day or Enoxaparin 1mg/kg BID or UFH Initiate referral to cardiac catheterisation labUnstable NSTE ACS
Eptifibatide or TirofibanConsider Intra-aortic balloon pumpEmergency referral to cath lab
Cardiac catheterization
in < 48 hours
ASA 160-325mg stat then 81mg dailyEnoxaparin 1mg/kg bid or Fondaparinux 2.5mg/sc/day for patients with prior cardiac history, non CVD or diabetes
Observe 8 - 12 hrsHigh Risk
FeaturesNo High Risk Features
Stress ECG/ Perfusion ScanHigh Risk Features
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 <0.001
*HR (95% Cl): 0.44 (0.39-0.50); **HR (95* Cl): 0.55 (0.41-0.74)
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 7 NS
Requiring surgery to
stop bleeding
77 41 <0.001
Transfusion 287 164 <0.001
Retroperitoneal 37 9 <0.001
Associated with death
at study end
79 38 <0.001
OASIS 5 Investigators. N Engl J Med 2006; 354:1464-76
Maj
or B
leed
GFR mL/min/1.73m2
0.10
0.00
0.02
0.08
40 60 80
0.04
0.06
100 120 140
Enoxaparin
Fondaparinux
Fox KAA. Ann Int Med 2007; 147: 304-310
Major Bleeding Lower with Fondaparinux Irrespective of Renal Function
(dose adjusted for renal function)
The Benefit of Fondaparinux is Consistent Irrespective of the GRACE Risk Score, Supporting its Use in a Broad Range of Patients with NSTEMI
0
2
4
6
8
10
12
<100 100 - 126 >126Low risk Intermediate risk High risk
GRACE Score GRACE Score
<100 100 - 126 >126Low risk Intermediate risk High risk
4.55.2 5.3 5.2
7.5 7.2
HR 1.170.93-1.48
HR 0.960.79-1.18
HR 0.960.81-1.15
Death, MI and RI at 9 days (%) Major bleeding at 9 days (%)
HR 0.420.28-0.63
HR 1.680.53-0.88
HR 0.450.35-1.58
2.7
1.1
4.0
2.7
5.4
2.5
Enoxaparin Fondaparinus
Joyner C. et al. JACC 2006;47(4) Suppl A:abstract 1018-223
0
2
4
6
8
10
12
20.0
10.0
30.0
40.0
50.0
<2 hrs 2 – 12 hrs 12 – 24 hrs
Time from randomisation
1432723
Angiography
PCl
0.0
24 – 72 hrs Total < 72 hrs
2199
1039
3651
1658
8919
4254
1637
834
A High Proportion of Patients Underwent an Early Invasive Strategy
Mehta S. Presented at ESC 2007 Scientific Session Oral Presentation
Net Clinical Benefit Favours Fondaparinux in Patients Undergoing PCl and Early PCl
Mehta SR. JAAC 2007, in press
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 <0.00001
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
Major Bleeding 4.9 2.3 0.48 0.0005
Death, MI Stroke, Major Bleeing
9.5 7.3 0.76 0.005
No UFH Prior to PCl UFH Prior to PCl
Enox
(%)
Fonda (%)
HR
(95% Cl)
Enox
(%)
Fonda
(%)
HR
(95% Cl)
No. randomized 810 793 80 75
Death/MI/Stroke 60 (7.4) 57 (7.2) 0.97
(0.68-1.40)
5 (6.3) 3 (4.0) 0.62
(0.15-2.61)
Major Bleed 35 (4.3) 25 (3.3) 0.75
(0.45-1.25)
5 (6.2) 1 (1.3) 0.21
(0.02-1.79)
Catheter Thrombus 4 (0.5) 9 (1.1) 2.30
(0.71-7.4)
0 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
Catheter Thrombus in Both Groups Virtually Eliminated After Protocal Amendment
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 0.18-1.11
UFH or equivalent placebo mandated by protocol during PCl
1.1
(n=1229)
0.4
(n=1279)
0.34 0.12-0.95
Open label UFH 2.7
(n=598)
1.3
(n=543)
0.48 0.20-1.17
Overall 1.5
(n=3104)
0.6
(n=3135)
0.42 0.24-071
Mean Dose of UFH for PCI Used in OASIS 5:47 units/kg
Yusuf S. et al. N Engl J Med 2006; 354:2829
Overall Enoxaparin Fondaparinux
(during blind study drug administration)
3.5%
1.6%
4.8%
2.4%2.3%
0.9%
Fondaparinux Reduces Major Bleeding in PCl Patients with Both Radial and Femoral Access
Hamon M, Mehta S. et al. AHA Scientific Sessions 2006 Abstract No. 9796
Femoral Radial
9 da
y ev
ents
(%
)