Download - 30 Day to 6 Month Death
![Page 1: 30 Day to 6 Month Death](https://reader036.vdocument.in/reader036/viewer/2022062314/568148b2550346895db5c959/html5/thumbnails/1.jpg)
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)
![Page 2: 30 Day to 6 Month Death](https://reader036.vdocument.in/reader036/viewer/2022062314/568148b2550346895db5c959/html5/thumbnails/2.jpg)
How Might Bleeding Increase Long -Term Mortality?
•Hemodynamic compromise
•Hyperadrenergic state
•Transfusion – induced microcirculatory disorder, NO depletion, immunologic effects
•Inflammatory response
•Discontinuation of antithrombotics
![Page 3: 30 Day to 6 Month Death](https://reader036.vdocument.in/reader036/viewer/2022062314/568148b2550346895db5c959/html5/thumbnails/3.jpg)
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
![Page 4: 30 Day to 6 Month Death](https://reader036.vdocument.in/reader036/viewer/2022062314/568148b2550346895db5c959/html5/thumbnails/4.jpg)
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
![Page 5: 30 Day to 6 Month Death](https://reader036.vdocument.in/reader036/viewer/2022062314/568148b2550346895db5c959/html5/thumbnails/5.jpg)
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)
![Page 6: 30 Day to 6 Month Death](https://reader036.vdocument.in/reader036/viewer/2022062314/568148b2550346895db5c959/html5/thumbnails/6.jpg)
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
![Page 7: 30 Day to 6 Month Death](https://reader036.vdocument.in/reader036/viewer/2022062314/568148b2550346895db5c959/html5/thumbnails/7.jpg)
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)
![Page 8: 30 Day to 6 Month Death](https://reader036.vdocument.in/reader036/viewer/2022062314/568148b2550346895db5c959/html5/thumbnails/8.jpg)
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
![Page 9: 30 Day to 6 Month Death](https://reader036.vdocument.in/reader036/viewer/2022062314/568148b2550346895db5c959/html5/thumbnails/9.jpg)
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
![Page 10: 30 Day to 6 Month Death](https://reader036.vdocument.in/reader036/viewer/2022062314/568148b2550346895db5c959/html5/thumbnails/10.jpg)
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
![Page 11: 30 Day to 6 Month Death](https://reader036.vdocument.in/reader036/viewer/2022062314/568148b2550346895db5c959/html5/thumbnails/11.jpg)
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
![Page 12: 30 Day to 6 Month Death](https://reader036.vdocument.in/reader036/viewer/2022062314/568148b2550346895db5c959/html5/thumbnails/12.jpg)
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
![Page 13: 30 Day to 6 Month Death](https://reader036.vdocument.in/reader036/viewer/2022062314/568148b2550346895db5c959/html5/thumbnails/13.jpg)
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
(%
)