VBWG

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OASIS-5

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

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US hospital discharges in ACS
Acute coronary syndromes
1.67 million hospital discharges/year
STEMI
UA/NSTEMI
1.17 million
500,000
AHA. Heart Disease and Stroke Statistics2005
Update.
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OASIS-5 Background

• The combined use of anticoagulants, antiplatelet
  agents, and invasive coronary procedures in a
  routine early invasive strategy reduces ischemic
  coronary events but also increases bleeding in
  selected patients with ACS
• OASIS-5 was conducted to assess whether
  fondaparinux, a selective inhibitor of factor Xa,
  would preserve the anti-ischemic benefits of
  enoxaparin and further reduce bleeding

MICHELANGELO OASIS 5 Steering Committee. Am
Heart J. 20051501107-14.OASIS-5 Investigators.
N Engl J Med. 20063541464-76.
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OASIS-5 Hypotheses

• In the acute treatment of patients with UA/NSTEMI
• fondaparinux is
• Noninferior to enoxaparin in preventing death,
  MI, or refractory ischemia through day 9
• Superior to enoxaparin as determined by lower
  major bleeding events through day 9
• Superior to enoxaparin in benefit/risk balance as
  determined by lower rate of death, MI, refractory
  ischemia, and major bleeding

MICHELANGELO OASIS 5 Steering Committee. Am
Heart J. 20051501107-14.OASIS-5 Investigators.
N Engl J Med. 20063541464-76.
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OASIS-5 Study design
Patients with NSTE ACS, chest discomfort lt24
hours,?2 Age gt60 y, ? ST segment, ? cardiac
biomarkers
ASA, clopidogrel, GP IIb/IIIa,planned cath/PCI
per local practice
Randomize N 20,078
Fondaparinux2.5 mg sc qd
Enoxaparin1 mg/kg sc bid
Outcomes Primary Efficacy Death, MI, refractory
ischemia at 9 d Safety Major bleeding at 9
d Benefit/risk Death, MI, refractory ischemia,
major bleeding at 9 d Secondary Primary outcomes
plus each component at 30 d and 6 mo
MICHELANGELO OASIS 5 Steering Committee. Am
Heart J. 20051501107-14.
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OASIS-5 Baseline characteristics
OASIS-5 Investigators. N Engl J Med.
20063541464-76.
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OASIS-5 Medical history

OASIS-5 Investigators. N Engl J Med.
20063541464-76.
8
OASIS-5 Concomitant in-hospital medications
following randomization

OASIS-5 Investigators. N Engl J Med.
20063541464-76.
9
OASIS-5 Treatment effect on primary efficacy
outcome at 9 days
Death, MI, refractory ischemia
HR 1.01
0.06
(0.90-1.13)
0.05
Fondaparinux
0.04
Cumulativeevent rate
0.03
0.02
Enoxaparin
0.01
0
0
1
2
3
4
5
6
7
8
9
Time (days)
OASIS-5 Investigators. N Engl J Med.
20063541464-76.
10
OASIS-5 Treatment effect on primary safety
outcome at 9 days
Major bleeding
0.06
Enoxaparin
0.04
HR 0.52 (0.44-0.61) P lt 0.001
0.03
Cumulativeevent rate
0.02
Fondaparinux
0.01
0
0
1
2
3
4
5
6
7
8
9
Time (days)
OASIS-5 Investigators. N Engl J Med.
20063541464-76.
11
OASIS-5 Net clinical benefit at 9 days
Death, MI, refractory ischemia, major bleeding
HR 0.81
(0.73-0.89)
0.08
P lt 0.001
Enoxaparin
0.06
Fondaparinux
Cumulativeevent rate
0.04
0.02
0
0
1
2
3
4
5
6
7
8
9
Time (days)
OASIS-5 Investigators. N Engl J Med.
20063541464-76.
12
OASIS-5 Primary and secondary efficacy outcomes
at 9 days

Fondaparinuxbetter
Enoxaparin better
Death/MI/RI
Prespecifiednoninferiority margin 1.185 P
0.007
Death/MI
Death
MI
RI
0.6
0.8
1
1.2
Hazard ratio (95 CI)
RI refractory ischemia
OASIS-5 Investigators. N Engl J Med.
20063541464-76.
13
OASIS-5 Primary and secondary efficacy outcomes
at 30 days

Fondaparinux (n 10,057)
Enoxaparin (n 10,021)
Fondaparinuxbetter
Enoxaparin better
Death/MI/RI
8.0
8.6
Death/MI
6.2
6.8
Death
2.9
3.5
MI
3.9
4.1
RI
2.2
2.2
0.6
0.8
1
1.2
Hazard ratio
P 0.13P 0.02
OASIS-5 Investigators. N Engl J Med.
20063541464-76.
14
OASIS-5 Death, MI, refractory ischemia at 6
months
Enoxaparin
HR 0.93(0.86-1.00) P 0.06
0.14
0.12
Fondaparinux
0.10
Cumulativeevent rate
0.08
0.06
0.04
0.02
0
0
20
40
60
80
100
120
140
160
180
Time (days)
OASIS-5 Investigators. N Engl J Med.
20063541464-76.
15
OASIS-5 Net clinical benefit at 6 months
Death, MI, refractory ischemia, major bleeding
HR 0.86(0.81-0.93) P lt 0.001
Enoxaparin
0.20
0.15
Fondaparinux
0.10
Cumulativeevent rate
0.05
0
0
20
40
60
80
100
120
140
160
180
Time (days)
OASIS-5 Investigators. N Engl J Med.
20063541464-76.
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OASIS-5 Primary and secondary efficacy outcomes
at 6 months

Fondaparinuxbetter
Enoxaparin better
Death/MI/RI
Death/MI
Death
MI
RI
0.6
0.8
1
1.2
Hazard ratio (95 CI)
P 0.06P 0.05
OASIS-5 Investigators. N Engl J Med.
20063541464-76.
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OASIS-5 Summary
At 9 days

• Primary outcome (death, MI, refractory ischemia)
• Fondaparinux was similar to enoxaparin in
  reducing the risk of ischemic events
• Primary safety outcome
• Rate of major bleeding was significantly lower
  for fondaparinux vs enoxaparin
• Benefit/risk assessment
• Rate of combined death, MI, refractory ischemia,
  and major bleeding was significantly lower for
  fondaparinux vs enoxaparin

OASIS-5 Investigators. N Engl J Med.
20063541464-76.
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OASIS-5 Summary, contd

• Overall, durable long-term results were observed
  with fondaparinux vs enoxaparin results occurred
  early and remained consistent through study end
• Strong trend toward lower rate of death, MI, or
  refractory ischemia at 30 days (P 0.13) through
  6 months (P 0.06)

• Net clinical benefit in favor of fondaparinux at
  6 months was demonstrated by significantly lower
  rate of combined death, MI, refractory ischemia,
  major bleeding (P lt 0.001)

OASIS-5 Investigators. N Engl J Med.
20063541464-76.