Transcript OASIS-5 Results - Clinical Trial Results
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 Xa AT Xa Fondaparinux Recycled
Turpie AGG et al. N Engl J Med. 2001;344:619.
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
UFH indicated
Randomization
Fondaparinux 2.5 mg Placebo Fondaparinux 2.5 mg UFH
Primary Efficacy Outcome Death/MI at 30 Days
UFH/Placebo Fondaparinux HR 0.86 95% CI 0.77-0.96
P=0.008
0 3 6 9 12 15 Days 18 21 24 27 30
Primary Efficacy Outcome Death/MI at 30 Days
No. of Patients Death or Re-MI
No. of Events (%) Control Fonda HR
6056 11.2
6036 9.7
0.86
95% CI
0.77-0.96
P
0.008
Death Reinfarction 8.9
3.0
7.8
0.87
0.77-0.98
0.026
2.5
0.81
0.65-1.01
0.057
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 Days 108 126 144 162 180
Efficacy of Fondaparinux by Strata on Death/MI at Study End No. of Events (%) Control Fonda HR 95% CI
15.9
0.87
0.76-0.99
Stratum I (n = 5658) (Fonda vs. Placebo) 17.3
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 N
12092
UFH/Placebo
11.2%
Fonda
9.7%
Interaction P value Overall Initial Reperfusion Rx
None Thrombolytic Primary PCI 2867 5436 3789
GRACE Risk Score
< 112 >=112 5958 6134 15.1
13.6
4.9
4.3
18.0
12.2
10.9
6.0
4.6
14.5
0.04
0.03
0.5
0.7 0.8
1.0 1.2 1.4 1.6
2.0
Fonda better 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 Fatal ICH
Control Fonda
79 (1.3%) 49 61 (1.0%) 35 10 11 Retroperitoneal 2 0 Cardiac Tamponade Hg drop ≥ 5 g/dL 48 17 28 19
HR
0.77
0.72
1.10
0.59
1.12
95% CI
0.55-1.08
P
0.13
0.47-1.10
0.47-2.60
0.58-2.15
0.13
0.82
0.37-0.93
0.02
0.74
Severe Hemorrhage by type of reperfusion therapy at 180 Days No. of Events
None Thrombolytics Primary PCI
Control Fonda HR 95% CI
1.8% 2.3% 1.0% 1.6% 1.6% 0.84
0.47-1.50
0.66
0.44-0.98
1.2% 1.18
0.63-2.22
P
0.55
0.04
0.60
No Reperfusion
Death and Net Clinical Benefit at Study End
Death HR (95% CI)
0.84
(0.69-1.01)
P
0.06
Death/MI/Stroke/ Severe Hemorrhage HR (95% CI)
0.81
(0.69-0.96)
P
0.016
Thrombolytic 1 o PCI Overall 0.85
(0.73-0.99) 1.09
(0.83-1.44) 0.88
(0.79-0.99) 0.04
0.52
0.029
0.83
(0.73-0.95) 1.12
(0.90-1.39) 0.88
(0.80-0.97) 0.007
0.29
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
≥ 75 Yr ≥ 75 Yr ≥ 75 Yr ≥ 75 Yr
Death and MI at 30 days
≥ 75 Yr ≥ 75 Yr ≥ 75 Yr ≥ 75 Yr
Death and MI at 30 days
Severe hemorrhage at 30 days
Net clinical benefit
Death/MI/s ev.hemorr
hage Control Fonda difference <75 >= 75 10.0% 25.6% 8.6% 22.5% 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