OASIS-5 Results - Clinical Trial Results

Report
Efficacy and Safety of
Fondaparinux in Elderly Patients
With ST-Segment Elevation
Myocardial Infarction:
Data From the OASIS 6 Trial
Ron J.G. Peters, MD
Cardiologist
Department of Cardiology
University of Amsterdam
Amsterdam, Netherlands
Efficacy and safety of
fondaparinux in
elderly patients with STEMI
results of the OASIS 6 trial
RJ Peters, C Joyner, JP Bassand,
R Afzal, S Chrolavicius, JW Eikelboom,
SR Mehta, Fox KAA, S Yusuf,
For the OASIS 6 investigators
Disclosure
Funded by Organon, Sanofi-Aventis, GSK
All authors have received grants and honoraria
from these companies and from several others
Fondaparinux:
Mechanism of Action
Intrinsic
pathway
Extrinsic
pathway
Antithrombin
AT
AT
Fondaparinux
Recycled
Turpie AGG et al. N Engl J Med. 2001;344:619.
AT
Xa
Xa
II
Fibrinogen
IIa THROMBIN
Fibrin clot
OASIS 6: Randomized, Double Blind,
Double Dummy
12,000 Patients with STEMI < 12 h of symptom onset
Inclusion: ST   2 mm prec leads or  1 mm limb leads
Exclusion: Contra-ind. for anticoagulant, INR>1.8, pregnancy, ICH<12 mo.
Lytics (SK, TPA, TNK, RPA), Primary PCI or no reperfusion (eg. late)
Stratification
UFH not indicated
Randomization
Fondaparinux
2.5 mg
Placebo
UFH indicated
Randomization
Fondaparinux
2.5 mg
UFH
0.02 0.04 0.06 0.08 0.10 0.12
UFH/Placebo
Fondaparinux
HR 0.86
95% CI 0.77-0.96
P=0.008
0.0
Cumulative Hazard
Primary Efficacy Outcome
Death/MI at 30 Days
0
3
6
9
12
15
Days
18
21
24
27
30
Primary Efficacy Outcome
Death/MI at 30 Days
No. of Events (%)
Control Fonda HR 95% CI
P
No. of Patients
6056
6036
Death or Re-MI
11.2
9.7
0.86
0.77-0.96
0.008
Death
8.9
7.8
0.87
0.77-0.98
0.026
Reinfarction
3.0
2.5
0.81
0.65-1.01
0.057
0.0 0.02 0.04 0.06 0.08 0.10 0.12
Cumulative Hazard
Death at Study End
(3 or 6 months)
UFH/Placebo
Fondaparinux
HR 0.88
95% CI 0.79-0.99
P=0.029
0
18
36
54
72
90
108
Days
126
144
162
180
Efficacy of Fondaparinux by Strata
on Death/MI at Study End
No. of Events (%)
Control Fonda
HR
95% CI
Stratum I (n = 5658)
(Fonda vs. Placebo)
17.3
15.9
0.87
0.76-0.99
Stratum II (n = 6434)
(Fonda vs. UFH)
12.7
11.2
0.88
0.76-1.02
Pre-Specified Subgroup Analyses
Death or MI at 30 days
Overall
N UFH/Placebo
12092
11.2%
Interaction
P value
Fonda
9.7%
Initial Reperfusion Rx
0.04
None
2867
15.1
12.2
Thrombolytic
5436
13.6
10.9
Primary PCI
3789
4.9
6.0
GRACE Risk Score
0.03
< 112
5958
4.3
4.6
>=112
6134
18.0
14.5
0.5
0.7 0.8
Fonda better
1.0 1.2 1.4 1.6
2.0
UFH/Plac better
Hazard Ratio
Severe Hemorrhage
definition




Fatal
Intracranial
Cardiac tamponade
Clinically significant hemorrhage with
decrease Hb > 5 gm/dl with each unit of
transfusion counting for 1 gm/dl Hb
Severe Hemorrhage at 9 Days
No. of Events
Severe Hemorrhage
Control Fonda HR
79
61
0.77
(1.3%) (1.0%)
95% CI
P
0.55-1.08 0.13
Fatal
49
35
0.72
0.47-1.10
0.13
ICH
10
11
1.10
0.47-2.60
0.82
Retroperitoneal
2
0
-
-
-
Cardiac Tamponade
48
28
0.59
0.37-0.93
0.02
Hg drop ≥ 5 g/dL
17
19
1.12
0.58-2.15
0.74
Severe Hemorrhage by type of
reperfusion therapy at 180 Days
No. of Events
Control Fonda HR 95% CI
P
None
1.8%
1.6% 0.84
0.47-1.50
0.55
Thrombolytics
2.3%
1.6% 0.66
0.44-0.98
0.04
Primary PCI
1.0%
1.2% 1.18
0.63-2.22
0.60
Death and Net Clinical Benefit at
Study End
Death
No
Reperfusion
HR
(95% CI)
0.84
(0.69-1.01)
P
0.06
Death/MI/Stroke/
Severe Hemorrhage
HR
P
(95% CI)
0.81
0.016
(0.69-0.96)
Thrombolytic
0.85
(0.73-0.99)
0.04
0.83
(0.73-0.95)
0.007
1o PCI
1.09
(0.83-1.44)
0.52
1.12
(0.90-1.39)
0.29
Overall
0.88
(0.79-0.99)
0.029
0.88
(0.80-0.97)
0.009
Elderly patients with STEMI




Higher risk of adverse outcome
Higher risk of bleeding with thrombolytics
Higher risk of bleeding with
anticoagulants
Net clinical outcome not predictable
Elderly patients in OASIS 6
methods




Post hoc analysis
≥ 75 years versus < 75 years
Primary endpoints as in main study
Net clinical benefit: death, MI, severe
hemorrhage at 30 days
Death and MI at 30 days
≥ 75 Yr
≥ 75 Yr
≥ 75 Yr
≥ 75 Yr
Death and MI at 30 days
≥ 75 Yr
≥ 75 Yr
≥ 75 Yr
≥ 75 Yr
Severe hemorrhage at 30 days
Net clinical benefit
Death/MI/s
ev.hemorr
hage
<75
>= 75
Control
10.0%
25.6%
Fonda
8.6%
22.5%
difference
HR
1.4%
0.85
(0.74-0.97)
3.2%
0.87
(0.72-1.05)
conclusions
In patients with STEMI who are not
treated with PPCI:


The efficacy and safety of fondaparinux
as compared to control treatment are
consistent across age groups
Consequently, the net clinical benefit of
fondaparinux is consistent across age
groups

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