VBWG

1
OASIS-6

• The Sixth Organization to Assess Strategies in
  Acute Ischemic Syndromes trial

2
OASIS-6 Background and hypothesis

• There is a clear need for safe and effective
  antithrombotic agents for STEMI patients
• In clinical trials, unfractionated heparin,
  direct thrombin inhibitors, and enoxaparin have
  failed to demonstrate significant mortality
  reductions and lower bleeding rates in STEMI
  patients
• Compared to standard antithrombotic therapies,
  does fondaparinux prevent CV events,
  revascularization, and mortality when initiated
  early in a broad range of STEMI patients?

OASIS-6 Trial Group. JAMA. 20062951519-30.
3
OASIS-6 Study design
Patients with STEMI randomized lt12 h of symptom
onsetN 12,092
Stratum IUFH not indicated (receiving
thrombolytics)(n 5658)
Stratum IIUFH indicated(receiving tPA or
scheduled PCI)(n 6434)
UFH 60 IU/kg IV bolus/12 IU/kg 2448 h infusion
placebo(n 3221)
Fondaparinux 2.5 mg qd placebo(n 3213)
Placebo(n 2835)
Fondaparinux 2.5 mg qd(n 2823)
Primary outcome Composite of death or
reinfarction at 30 days Main safety
outcome Severe bleeding
OASIS-6 Trial Group. JAMA. 20062951519-30.
Up to 8 days (or earlier discharge)
4
OASIS-6 Baseline characteristics
Strata 1 and 2 combined
OASIS-6 Trial Group. JAMA. 20062951519-30.
5
OASIS-6 Medical history
Strata 1 and 2 combined

OASIS-6 Trial Group. JAMA. 20062951519-30.
6
OASIS-6 Concomitant in-hospital medications
following randomization
Strata 1 and 2 combined

OASIS-6 Trial Group. JAMA. 20062951519-30.
Other medications lt1 each
7
OASIS-6 Treatment effect on primary efficacy
outcome at 30 days
Composite of death, MI
0.14
0.12
0.10
0.08
Cumulative event rate
0.06
HR 0.86(0.770.96)P 0.008
0.04
0.02
0
0
3
6
9
12
16
18
21
24
27
30
Days
UFH or placebo
Fondaparinux
OASIS-6 Trial Group. JAMA. 20062951519-30.
8
OASIS-6 Severe bleeding at 30 days
Modified TIMI criterion
0.016
0.014
0.012
0.010
Cumulative event rate
0.008
HR 0.79(0.581.09)P 0.15
0.006
0.004
0.002
0
0
3
6
9
12
16
18
21
24
27
30
Days
UFH or placebo
Fondaparinux
OASIS-6 Trial Group. JAMA. 20062951519-30.
9
OASIS-6 Net clinical benefit
Death, MI, severe bleeding

UFH or placebo
Favors fondaparinux
Favors UFH or placebo
Fondaparinux
P
9.3 11.6 14.7
7.7 10.0 12.9
9 days 30 days 6 months
0.003 0.005 0.005
0.8
1.0
1.2
Hazard ratio(95 CI)
OASIS-6 Trial Group. JAMA. 20062951519-30.
10
OASIS-6 Treatment effect on primary outcome at
30 daysSubgroup analyses
Composite of death, MI at 30 days

Favors fondaparinux
Favors UFH or placebo
UFH or placebo
Fondaparinux
Characteristic
11.2 8.3 12.2 10.9 6.0
14.08.7 15.1 13.6 4.9
Stratum UFH not indicated UFH
indicated Initial reperfusion therapy None Thro
mbolytic Primary PCI
0.5
1
2.0
Hazard ratio(95 CI)
OASIS-6 Trial Group. JAMA. 20062951519-30.
11
OASIS-6 Reduction in death and MI at study end
Death
MI
0.16
0.16
0.14
0.14
HR 0.81(0.670.97)P 0.03
0.12
0.12
0.10
0.10
Cumulativeevent rate
0.08
0.08
HR 0.88(0.790.99)P 0.03
0.06
0.06
0.04
0.04
0.02
0.02
0
0
0
30
60
90
120
150
180
0
30
60
90
120
150
180
Days
Days
UFH or placebo
Fondaparinux
All patients followed for 3 months n 6976
followed for 6 months
OASIS-6 Trial Group. JAMA. 20062951519-30.
12
OASIS-6 Conclusion

• Primary efficacy outcome at 30 days
• Fondaparinux significantly reduced death and
  reinfarction vs UFH/placebo
• Main safety outcome
• Trend to lower rate of severe bleeding
• Overall, results occurred early (9 days) and
  remained consistent through study end
• Significant reduction in death (12, P 0.03)
  and MI (19, P 0.03)
• Benefit/risk balance
• Rate of combined death, MI, and severe bleeding
  was significantly lower for fondaparinux vs
  UFH/placebo
• Subgroup analysis
• Benefit shown in 5436 patients who received
  thrombolytic therapyLittle benefit in 3789
  patients who underwent primary PCI

OASIS-6 Trial Group. JAMA. 20062951519-30.
13
OASIS-6 Summary

• Fondaparinux demonstrated a moderate reduction in
  mortality and reinfarction vs UFH/placebo
• Unlike other antithrombotic agents (eg, LMW
  heparin, direct thrombin inhibitors, intravenous
  antiplatelet agents), fondaparinux reduced deaths
  and reinfarction without increased bleeding or
  hemorrhagic stroke
• There appears to be little advantage in using
  fondaparinux as the initial treatment in patients
  undergoing primary PCI

OASIS-6 Trial Group. JAMA. 20062951519-30.
14
The OASIS program Safety and efficacy of
fondaparinux in a broad range of patients with ACS

• OASIS-5 N 20,078 with UA/NSTEMI Fondaparinux
  vs enoxaparin
• Similar efficacy in reducing risk of death, MI,
  and refractory ischemiaat 9 days
• Significantly lower rate of major bleeding (P lt
  0.001) at 9 days
• OASIS-6 N 12,092 with STEMI Fondaparinux vs
  UFH/placebo
• Significantly lower rate of death and
  reinfarction at 30 days (P 0.008)
• Benefit principally in patients who did not
  undergo primary PCI
• Nonsignificant trend towards lower rate of severe
  bleeding at 30 days
• In both trials, efficacy and net clinical benefit
  remained consistent through study end

OASIS-5 Investigators. N Engl J Med. 2006
epublished March 14.OASIS-6 Trial Group. JAMA.
20062951519-30.