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

VBWG US hospital discharges in ACS AHA. Heart Disease and Stroke Statistics–2005 Update 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: OASIS-5 Investigators. N Engl J Med. 2006;354:

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

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: 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

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

VBWG OASIS-5: Medical history Enoxaparin (n = 10,021) Fondaparinux (n = 10,057) MI 25.7 PCI/CABG Stroke Heart failure Hypertension Diabetes Current/former smoker Any ECG abnormality ST  ≥1 mm % OASIS-5 Investigators. N Engl J Med. 2006;354:

VBWG OASIS-5: Concomitant in-hospital medications following randomization Enoxaparin (n = 10,021) Fondaparinux (n = 10,057) ASA97.5 Clopidogrel/ticlopidine UFH ACEI/ARB β-blocker Lipid-lowering agent % OASIS-5 Investigators. N Engl J Med. 2006;354:

VBWG OASIS-5: Treatment effect on primary efficacy outcome at 9 days Death, MI, refractory ischemia Enoxaparin Cumulative event rate Time (days) Fondaparinux HR 1.01 ( ) OASIS-5 Investigators. N Engl J Med. 2006;354:

VBWG OASIS-5: Treatment effect on primary safety outcome at 9 days HR 0.52 ( ) P < Enoxaparin Fondaparinux Time (days) 0.06 Major bleeding Cumulative event rate OASIS-5 Investigators. N Engl J Med. 2006;354:

VBWG OASIS-5: Net clinical benefit at 9 days Death, MI, refractory ischemia, major bleeding Enoxaparin Time (days) Fondaparinux HR 0.81 ( ) P < Cumulative event rate OASIS-5 Investigators. N Engl J Med. 2006;354:

VBWG OASIS-5: Primary and secondary efficacy outcomes at 9 days Prespecified noninferiority margin = P = RI = refractory ischemia Hazard ratio (95% CI) Fondaparinux better Enoxaparin better Death/MI/RI Death/MI Death MI RI Fondaparinux (n = 10,057) Enoxaparin (n = 10,021) % OASIS-5 Investigators. N Engl J Med. 2006;354:

VBWG 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 Fondaparinux (n = 10,057) Enoxaparin (n = 10,021) % Fondaparinux better Enoxaparin better OASIS-5 Investigators. N Engl J Med. 2006;354:

VBWG OASIS-5: Death, MI, refractory ischemia at 6 months Enoxaparin Fondaparinux HR 0.93 ( ) P = 0.06 Time (days) Cumulative event rate OASIS-5 Investigators. N Engl J Med. 2006;354:

VBWG OASIS-5: Net clinical benefit at 6 months Enoxaparin Time (days) Fondaparinux Death, MI, refractory ischemia, major bleeding HR 0.86 ( ) P < Cumulative event rate 0.20 OASIS-5 Investigators. N Engl J Med. 2006;354:

VBWG OASIS-5: Primary and secondary efficacy outcomes at 6 months Death/MI/RI* Death/MI † Death † MI RI Hazard ratio (95% CI) Enoxaparin (n = 10,021) % Fondaparinux better Enoxaparin better Fondaparinux (n = 10,057) *P = 0.06 † P = 0.05 OASIS-5 Investigators. N Engl J Med. 2006;354:

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:

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: