Heparin, enoxaparin & fondaparinux in ACS

in

NSTE-ACS

Heparin: Systematic review of 6 RCTs (3 were double-blind) published 1988-1995

  • P: NSTE-ACS patients treated with ASA (n=1353)
  • I: Heparin bolus + infusion x2-7 days
  • C: Placebo/no treatment
  • O:
    • Death/MI: Heparin 7.9%, control 10.4% (NNT 40), OR 0.67 (0.45-0.99)
    • Recurrent angina: OR 0.94 (0.58-1.54)
    • Revascularization: OR 1.25 (0.76-2.06)
    • Major bleed: OR 1.88 (0.60-5.87)

 

Enoxaparin (A to Z, ESSENCE, SYNERGY, TIMI 11B)

 

Fondaparinux: OASIS 5 - Double-blind non-inferiority RCT

  • P: NSTE-ACS (n=20,078)
    • Clopidogrel given to 2/3
  • I: Fondaparinux 2.5 mg  once daily up to 8 days or until discharge
  • C: Enoxaparin 1 mg/kg q12h (if CrCl <30: 1 mg/kg q24h) x2-8 days or until "clinically stable"
  • O @ day 9:
    • Primary outcome (death/MI/refractory ischemia): Fondaparinux 5.8%, enoxaparin 5.7%, HR 1.01 (0.90-1.13)
      • Death: 1.8% vs 1.9%
      • MI: 2.6% vs 2.7%
      • Refractory ischemia: 1.9% for both
    • Major bleed: 2.2% vs 4.1% (NNT 53), HR 0.52 (0.44-0.61)
  • O @ 180 days:
    • Primary outcome: 12.3% vs 13.2% (NNT 112), HR 0.93 (0.86-1.00)
      • Death: 5.8% vs 6.5%
    • Major bleed: 4.3% vs 5.8%, HR 0.72 (0.64-0.82)
  • Benefit & safety preserved in 1/3 of patients who underwent PCI during initial ACS hospitalization (in fondaparinux group, heparin given during PCI)

 

STEMI

Enoxaparin: (ASSENT 3, EXTRACT TIMI 25)

  • ASSENT 3
    • P: STEMI undergoing fibrinolysis with TNK (n6095)
    • I: Enoxaparin 30 mg IV bolus, then 1 mg/kg subcutaneously q12h continued for max 7 days
    • C: Heparin bolus, then infusion for at least 48h (also 3rd group given abciximab & no anticoagulant)
    • O @ 30 days:
      • Primary outcome (death, in-hospital re-infarction or refractory ischemia): Enoxaparin 11.4%, heparin 15.4% (NNT 25)
        • Death: 5.4% vs 6.0% (p=0.25)
        • Re-infarction: 2.7% vs 4.2%
        • Refractory ischemia: 4.6% vs 6.5%
      • ICH: 0.9% in both groups
      • Major bleed, non-ICH: 3.0% vs 2.2% (NNH 125)
  • EXTRACT TIMI 25
    • P: STEMI undergoing fibrinolysis (n=20,506)
    • I: Enoxaparin 30 mg IV bolus, then 1 mg/kg subcutaneously q12h continued for max 8 days or until discharge
      • If >75 y/o: No bolus, 0.75 mg/kg q12h
      • If CrCl <30 mL/min: 1 mg/kg q24h
    • C: Heparin infusion to aPTT 1.5-2.0x above normal, given for at least 48h
    • O @ 30 days:
      • Primary outcome (death/MI): Enoxaparin 9.9%, heparin 12.0% (NNT 48), RR 0.83 (0.77-0.90)
        • Death: 6.9% vs 7.5%
        • MI: 3.0% vs 4.5%
      • Urgent revascularization: 2.1% vs 2.8%
      • Major bleed: 2.1% vs 1.4% (NNH 143), RR 1.53 (1.23-1.89)

 

Fondaparinux: OASIS 6 - Double-blind RCT

  • P: STEMI (n=12,092)
  • I: Fondaparinux 2.5 mg daily (first dose IV if lytic/PCI) for up to 8 days or until discharge
  • C: Stratified by indication for placebo
    • No indication for heparin: Placebo
    • Indication for heparin (fibrin-specific thrombolytic or scheduled for 1o PCI): Heparin x1-2 days
  • O @ 30 days (only presenting data for those with indication for heparin)
    • Primary outcome (death/MI): Fondaparinux 8.3%, heparin 8.7%, HR 0.96 (0.81-1.13)
    • Major bleed: Fondaparinux 2.1%, heparin 2.3%, HR 0.93 (0.67-1.30)