Comparison of Fondaparinux and Enoxaparin in Acute Coronary Syndromes
Topic: Anticoagulation in acute coronary syndrome (unfractionated heparin and low molecular weight heparin)
Aim:
- Determine whether fondaparinux would preserve the anti-ischemic benefits of enoxaparin while reducing bleeding in patients with NSTEMI ACS
Design:
- Randomized, double blind, double dummy trial (intention to treat analysis)
Treatment:
- Fondaparinux (2.5 mg subcutaneous once daily for 8 days or until hospital discharge, whichever occurred first) plus placebo enoxaparin subcutaneous injection twice daily
Control:
- Placebo fondaparinux subcutaneous, plus enoxaparin (1 mg/kg twice daily subcutaneous, until clinical stability or between 2-8 days). Enoxaparin reduced to 1 mg/kg daily in patients with CrCl less than 30 mL/min
Cohort:
- 20,078 participants
Inclusion criteria:
- Patients meeting at least 2 out of 3 following criteria: at least 60 years old with ischemic symptoms, elevated cardiac biomarkers, or ischemic ECG changes
Exclusion criteria:
- Contraindication to anticoagulation, serum creatinine of at least 3mg/dL, recent hemorrhagic stroke, indication for anticoagulation other than ACS
Follow up:
- 6 months
Primary endpoint:
- Composite of death, myocardial infarction, or refractory ischemia at 9 days
Secondary endpoint:
- Death or MI
Main results:
- Mean age 67 years, 61% male
- Medications at randomization: aspirin 78%, clopidogrel or ticlopidine 32%, UFH 18%, LMWH 32%, ACE inhibitor or ARB 51%, beta-blocker 60%, CCB 22%, lipid-lowering agent 38%
- Procedures in hospital: Coronary angiography 63%, PCI 34%, CABG 9%
- Death, MI, or refractory ischemia after 9 days (primary endpoints): 5.8% vs. 5.7% (HR 1.01; CI 0.90-1.13; P = 0.007, non-inferiority; P=NS, superiority)
- Death or MI (secondary endpoints): 4.1% vs. 4.1% (HR 0.99; 95% CI 0.86-1.13; P=0.005, non-inferiority; p=NS, superiority)
- Major bleeding: 2.2% vs. 4.1% (HR 0.52; 95% CI 0.44-0.61; P<0.001; NNT=53)
- Death, MI, refractory ischemia, or major bleeding: 7.3% vs. 9.0% (HR 0.81; 95% CI 0.44-0.61; P<0.001; NNT=59)
- All catheter-related thrombi: 0.9% vs. 0.4% (RR 3.59; 95% CI 1.64-7.84; P=0.001)
TAKE AWAY: Among patients with NSTE-ACS, fondaparinux is non-inferior to enoxaparin in preventing death, myocardial infarction, or refractory ischemia, but associated with increased risk of catheter-related thrombosis.
