OASIS-5
description
Transcript of OASIS-5
![Page 1: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/1.jpg)
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
![Page 2: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/2.jpg)
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
![Page 3: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/3.jpg)
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.
![Page 4: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/4.jpg)
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
MICHELANGELO OASIS 5 Steering Committee. Am Heart J. 2005;150:1107-14.
OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.
![Page 5: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/5.jpg)
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
MICHELANGELO OASIS 5 Steering Committee. Am Heart J. 2005;150:1107-14.
ASA, clopidogrel, GP IIb/IIIa,planned cath/PCI per local practice
Randomize
N = 20,078Fondaparinux2.5 mg sc qd
Enoxaparin1 mg/kg sc bid
![Page 6: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/6.jpg)
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
OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.
![Page 7: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/7.jpg)
VBWG
OASIS-5: Medical history
Enoxaparin(n = 10,021)
Fondaparinux(n = 10,057)
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
%
OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.
![Page 8: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/8.jpg)
VBWG
OASIS-5: Concomitant in-hospital medications following randomization
Enoxaparin(n = 10,021)
Fondaparinux(n = 10,057)
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
%
OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.
![Page 9: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/9.jpg)
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)
OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.
![Page 10: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/10.jpg)
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
Cumulativeevent rate
OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.
![Page 11: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/11.jpg)
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
Cumulativeevent rate
OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.
![Page 12: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/12.jpg)
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
Fondaparinux(n = 10,057)
5.7
4.1
1.9
2.7
1.9
Enoxaparin(n = 10,021)
%
OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.
![Page 13: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/13.jpg)
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
Fondaparinux(n = 10,057)
8.6
6.8
3.5
4.1
2.2
Enoxaparin(n = 10,021)
%
Fondaparinuxbetter
Enoxaparin better
OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.
![Page 14: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/14.jpg)
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)
Cumulativeevent rate
OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.
![Page 15: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/15.jpg)
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
Cumulativeevent rate
0.20
OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.
![Page 16: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/16.jpg)
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
Enoxaparin(n = 10,021)
%
Fondaparinuxbetter
Enoxaparin better
12.3
10.5
5.8
6.3
2.3
Fondaparinux(n = 10,057)
*P = 0.06†P = 0.05 OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.
![Page 17: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/17.jpg)
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
OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.
![Page 18: OASIS-5](https://reader035.fdocuments.in/reader035/viewer/2022062304/56814585550346895db2657e/html5/thumbnails/18.jpg)
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)
OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.