Anticoagulant Therapy in ACS

focused on fondaparinux
Unfractionated Heparin

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www.aafp.org
LMWH

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www.aafp.org
Fondaparinux: pharmacology

• Synthetic polysaccharide
• Indirect, selective factor Xa inhibitor
• Binds to antithrombin III
Fondaparinux: pharmacology

– Favorable pharmacokinetic profile after SC

administration
• 100% absorption into plasma
• Maximal concentration in 2h
• Relatively long half-life (17h)
• Predictable dose response, independent of age or sex
Donat, et al. 2002.
Fondaparinux: pharmacology

• Metabolism:
– 100% renal clearance (same as LMWH)
– No studies on renal dose-adjustment
• Thus, GFR < 30mL/min (≈ Cr > 265mmol/L) is a contraindication
 Pharmacologic comparison
Pharmacotherapy 23(6):772-787, 2003

Property UFH LMWH Fondaparinux

Source animal animal synthetic
T1/2 ~3h ~4h (variable) 17-21h
Bioavailability
30% >90% 100%
(SC)
Reticuloendothelial
Elimination renal renal
and renal
Induced HIT* 2-5% 1-2% Not observed
Inter or intra-
patient +++ ++ +
variability
aPTT
Monitoring Plt count nil
Plt count
Reversal Protamine Protamine FFP

* Discussed later
FONDAPARINUX PADA STEMI
FONDAPARINUX PADA NSTEMI/UAP
OASIS-5: Fondaparinux in UA/NSTEMI
N Engl J Med 2006;354:1464-76
OASIS-5: Fondaparinux in UA/NSTEMI
N Engl J Med 2006;354:1464-76
OASIS-5: Fondaparinux in UA/NSTEMI
N Engl J Med 2006;354:1464-76
 OASIS-6
JAMA. 2006;295:1519-1530

• Randomized, double-blinded, controlled trial

comparing fondaparinux (2.5mg sc daily) to usual
care (either placebo, or UFH)
• N = 12 092
• Inclusion:
– STEMI within 24h* onset of symptoms (shortened to
12h after 4300 pts)
• Exclusion:
– Contraindications to anticoagulation (including high
bleeding risk)
– Renal failure
 OASIS-6
JAMA. 2006;295:1519-1530

Primary End point: death/reinfarction at 30d

Fondaparinux vs UFH, death/reinfarction in patients undergoing primary PCI

 AHS Current Recommendations

• Don’t give fondaparinux to:

1. STEMI patients going directly to PCI
2. Patients with Renal failure (GFR <30 mL/min or Cr
<265mmol/L)
3. Patients going directly to the cath lab

• Fondaparinux can generally be used for all

other cases of ACS/NSTEMI as 2.5mg SC daily