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

2. 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

3. 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.

4. VBWG 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. 2005;150:1107-14. OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.

5. VBWG OASIS-5: Study design Patients with NSTE ACS, chest discomfort 60 y,  ST segment,  cardiac biomarkers Outcomes Primary:Efficacy Death, MI, refractory ischemia at 9 d SafetyMajor bleeding at 9 d Benefit/riskDeath, 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 = 20,078 Fondaparinux 2.5 mg sc qd Enoxaparin 1 mg/kg sc bid

6. VBWG OASIS-5: Baseline characteristics Enoxaparin (n = 10,021) Fondaparinux (n = 10,057) Age (years)66.6 Male (%)61.462.0 Time from pain onset (hours)12.7 Heart rate (bpm)73.0 Systolic BP (mm Hg)136.3136.6 Diagnosis at study entry (%) UA Suspected MI 45.1 54.9 45.6 54.4 OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.

7. VBWG OASIS-5: Medical history Enoxaparin (n = 10,021) Fondaparinux (n = 10,057) MI 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.

8. VBWG OASIS-5: Concomitant in-hospital medications following randomization Enoxaparin (n = 10,021) Fondaparinux (n = 10,057) ASA97.5 Clopidogrel/ticlopidine67.267.6 UFH31.222.0 ACEI/ARB76.174.9 β-blocker87.787.2 Lipid-lowering agent78.479.4 % OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.

9. VBWG OASIS-5: Treatment effect on primary efficacy outcome at 9 days Death, MI, refractory ischemia 01 0 0.01 0.02 0.03 0.04 0.05 0.06 23 Enoxaparin Cumulative event rate Time (days) Fondaparinux 456789 HR 1.01 (0.90-1.13) OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.

10. VBWG OASIS-5: Treatment effect on primary safety outcome at 9 days 0.04 0.03 0.02 0.01 0 0123456789 HR 0.52 (0.44-0.61) P < 0.001 Enoxaparin Fondaparinux Time (days) 0.06 Major bleeding Cumulative event rate OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.

11. VBWG OASIS-5: Net clinical benefit at 9 days Death, MI, refractory ischemia, major bleeding 01 0 0.02 0.04 0.06 0.08 23 Enoxaparin Time (days) Fondaparinux 456789 HR 0.81 (0.73-0.89) P < 0.001 Cumulative event rate OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.

12. VBWG OASIS-5: Primary and secondary efficacy outcomes at 9 days Prespecified noninferiority margin = 1.185 P = 0.007 RI = refractory ischemia 0.60.811.2 Hazard ratio (95% CI) Fondaparinux better 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.

13. VBWG 0.60.811.2 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) % Fondaparinux better Enoxaparin better OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.

14. VBWG OASIS-5: Death, MI, refractory ischemia at 6 months 020 0 0.02 0.04 0.06 0.08 0.10 0.12 0.14 4060 Enoxaparin Fondaparinux 80100120140160180 HR 0.93 (0.86-1.00) P = 0.06 Time (days) Cumulative event rate OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.

15. VBWG OASIS-5: Net clinical benefit at 6 months 020 0 0.10 0.05 0.15 4060 Enoxaparin Time (days) Fondaparinux 80100120140160180 Death, MI, refractory ischemia, major bleeding HR 0.86 (0.81-0.93) P < 0.001 Cumulative event rate 0.20 OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.

16. VBWG 0.60.811.2 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) % Fondaparinux better 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.

17. VBWG OASIS-5: Summary 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 At 9 days OASIS-5 Investigators. N Engl J Med. 2006;354:1464-76.

18. 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.