VBWG OASIS-5 The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes trial.

VBWG

OASIS-5OASIS-5

The Fifth The Fifth OOrganization to rganization to AAssess ssess SStrategies trategies in Acute in Acute IIschemic schemic SSyndromes trial yndromes trial

VBWG

US hospital discharges in ACS

AHA. Heart Disease and Stroke Statistics–2005 Update.

1.67 million hospital discharges/year

STEMI

1.17 million 500,000

Acute coronary syndromes

UA/NSTEMI

VBWG

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. 2005;150:1107-14.

OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.

VBWG

OASIS-5: Hypotheses

In the acute treatment of patients with UA/NSTEMIfondaparinux 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



VBWG

OASIS-5: Study design

Patients with NSTE ACS, chest discomfort <24 hours,2: Age >60 y, ST segment, cardiac biomarkers

Outcomes

Primary: Efficacy Death, MI, refractory ischemia at 9 dSafety Major bleeding at 9 dBenefit/risk Death, MI, refractory ischemia, major bleeding at 9 d

Secondary: Primary outcomes plus each component at 30 d and 6 mo


ASA, clopidogrel, GP IIb/IIIa,planned cath/PCI per local practice

Randomize

N = 20,078Fondaparinux2.5 mg sc qd

Enoxaparin1 mg/kg sc bid

VBWG

OASIS-5: Baseline characteristics

Enoxaparin(n = 10,021)

Fondaparinux(n = 10,057)

Age (years) 66.6 66.6

Male (%) 61.4 62.0

Time from pain onset (hours) 12.7 12.7

Heart rate (bpm) 73.0 73.0

Systolic BP (mm Hg) 136.3 136.6

Diagnosis at study entry (%) UA Suspected MI

45.154.9

45.654.4


VBWG

OASIS-5: Medical history



MI 25.7 25.7

PCI/CABG 19.5 20.1

Stroke 6.5 5.9

Heart failure 13.8 13.9

Hypertension 67.1 67.4

Diabetes 25.0 25.6

Current/former smoker 54.6 54.1

Any ECG abnormality 79.8 80.6

ST ≥1 mm 50.3 51.7

%


VBWG

OASIS-5: Concomitant in-hospital medications following randomization



ASA 97.5 97.5

Clopidogrel/ticlopidine 67.2 67.6

UFH 31.2 22.0

ACEI/ARB 76.1 74.9

β-blocker 87.7 87.2

Lipid-lowering agent 78.4 79.4

%


VBWG

OASIS-5: Treatment effect on primary efficacy outcome at 9 days

Death, MI, refractory ischemia

0 10

0.01

0.02

0.03

0.04

0.05

0.06

2 3

Enoxaparin

Cumulativeevent rate

Time (days)

Fondaparinux

4 5 6 7 8 9

HR 1.01 (0.90-1.13)


VBWG

OASIS-5: Treatment effect on primary safety outcome at 9 days

0.04

0.03

0.02

0.01

00 1 2 3 4 5 6 7 8 9

HR 0.52 (0.44-0.61)P < 0.001

Enoxaparin

Fondaparinux

Time (days)

0.06

Major bleeding



VBWG

OASIS-5: Net clinical benefit at 9 days

Death, MI, refractory ischemia, major bleeding

0 1

0

0.02

0.04

0.06

0.08

2 3

Enoxaparin

Time (days)

Fondaparinux

4 5 6 7 8 9

HR 0.81 (0.73-0.89) P < 0.001



VBWG

OASIS-5: Primary and secondary efficacy outcomes at 9 days

Prespecifiednoninferiority margin = 1.185

P = 0.007

RI = refractory ischemia

0.6 0.8 1 1.2

Hazard ratio (95% CI)

Fondaparinuxbetter

Enoxaparin better

Death/MI/RI

Death/MI

Death

MI

RI

5.8

4.1

1.8

2.6

1.9


5.7

4.1

1.9

2.7

1.9


%


VBWG

0.6 0.8 1 1.2

OASIS-5: Primary and secondary efficacy outcomes at 30 days

*P = 0.13†P = 0.02

Death/MI/RI*

Death/MI

Death†

MI

RI

Hazard ratio

8.0

6.2

2.9

3.9

2.2


8.6

6.8

3.5

4.1

2.2


%

Fondaparinuxbetter

Enoxaparin better


VBWG

OASIS-5: Death, MI, refractory ischemia at 6 months

0 20

0

0.02

0.04

0.06

0.08

0.10

0.12

0.14

40 60

Enoxaparin

Fondaparinux

80 100 120 140 160 180

HR 0.93(0.86-1.00) P = 0.06

Time (days)



VBWG

OASIS-5: Net clinical benefit at 6 months

0 20

0

0.10

0.05

0.15

40 60

Enoxaparin

Time (days)

Fondaparinux

80 100 120 140 160 180

Death, MI, refractory ischemia, major bleeding

HR 0.86(0.81-0.93)P < 0.001


0.20


VBWG

0.6 0.8 1 1.2

OASIS-5: Primary and secondary efficacy outcomes at 6 months

Death/MI/RI*

Death/MI†

Death†

MI

RI

Hazard ratio (95% CI)

13.2

11.4

6.5

6.6

2.4


%

Fondaparinuxbetter

Enoxaparin better

12.3

10.5

5.8

6.3

2.3


*P = 0.06†P = 0.05 OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.

VBWG

OASIS-5: Summary

• Primary outcome (death, MI, refractory ischemia)Fondaparinux was similar to enoxaparin in reducing the risk of ischemic events

• Primary safety outcomeRate of major bleeding was significantly lower for fondaparinux vs enoxaparin

• Benefit/risk assessmentRate of combined death, MI, refractory ischemia, and major bleeding was significantly lower for fondaparinux vs enoxaparin

At 9 days


VBWG

OASIS-5: Summary, cont’d

• 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 < 0.001)


VBWG OASIS-5 The Fifth Organization to Assess Strategies in Acute Ischemic Syndromes trial.

Documents

momichelangelo oasis

n engl j

refractory ischemia0100

primary outcomes

primary efficacy outcome

efficacy death

lower major bleeding

major bleeding0100