Heparin manufacturing Characteristics of ufh and lmwh chains

Heparin manufacturing

Characteristics of UFH and LMWH Chains

Sites of Anti-thrombotic Drug Action

Treatment—LMWH: Enoxaparin for Non ST  ACS TIMI 11B/ESSENCE Meta-Analysis of Death/MI

Enoxaparin Outcomes

TESSMA: TIMI 11B + ESSENCE Meta-Analysis 1 Yr Follow-up

Study Design and Protocol

Enoxaparin Meta-analysis Triple Composite Event Rates

Superior

• Superior

• Yield of the

• New strategy of

• Enoxaparin,

• Revascularization &

• GlYcoprotein IIb/IIIa Inhibitors

Enoxaparin UFH Unadjusted (n = 4993) (n = 4985) P-value

• Enoxaparin UFH Unadjusted (n = 4993) (n = 4985) P-value

• Death and MI (%) 14.0 14.5 0.396

• Death (%) 3.2 3.1 0.705

• MI (%) 11.7 12.7 0.135

LMWH in ACS/AMI and PCI

• Pre-Treatment +/- GP IIb/IIIa

• ESSENCE/TIMI-11b (n = 239)
• PEPCI (n = 48)
• NICE – 3 (n = 661)
• Collet Trial (n = 132)

• No Pre-Treatment +/- GP IIb/IIIa

• NICE – 1 (n = 828)
• NICE – 4 (n = 818)
• CRUISE (n = 129)
• Choussat Trial (n = 242)

• Post-Thrombolysis for AMI

• ASSENT – 3 (n = 590)
• ENTIRE / TIMI – 23 (n = 121 )

Performing angioplasty is like

• Performing angioplasty is like

• flying a jet airplane –

Enoxaparin in PCI

NICE 1 and NICE 4

• NICE 1 (n = 828)

• Enoxaparin
• 1 mg/kg IV
• without GP IIb/IIIa

NICE-1 and 4: Enoxaparin in PCI

NICE 1 and NICE 4

• Incidence of Major Bleeding

NICE 3 Protocol

NICE 3

CRUISE: Enoxaparin vs UFH in PCI with Eptifibatide

Anti-Xa Activity With LMW Heparin Administration

Enoxaparin pK Modeling 1 mg/kg sc

Enoxaparin in PCI in Patients with ACS

• 451 pts with UA/NQWMI rx’d with enoxaparin for 48 hrs.

• 293 underwent cath within 8 hrs of AM enox. dose

• 132 ad hoc PCI, no additional UFH/LMWH

• 30d: Death=1.5%, MI=3.0%, Maj. Bleeding = 0.8%

• Mean anti-Xa at PCI=0.98+0.03 IU/ml,

Enoxaparin in PCI

Monitoring of the anticoagulant effect

• Monitoring of the anticoagulant effect

• (anti-Xa effect) of enoxaparin on clotting

RapidPoint

Enoxaparin Key Principles

• Subcutaneous dosing

• delay between dose and effect (peak 3-4h)
• not therapeutic from dose 1
• steady-state only after 3-4 doses
• ~5% of patients still <0.6 anti-Xa IU/ml

• Cath lab considerations

• no monitoring available
• t½ of subq enox ~8h (sheath pull)
• adverse interactions between enox + UFH, enox + GP IIb/IIIa (↑ anticoagulation → bleeding, adverse events)
• pharmacodynamics of IV enox = IV UFH

Enoxaparin ED to Diagnostic Cardiac Catheterization

• ED (AMI, ACS):

• 1.0 mg/kg subq (0.75 mg/kg if age >75)
• (optional 30 mg IV bolus if age <75)

• inpatient: 1.0 mg/kg subq q12°

• dx cath:

• <12h since subq dose: no additional anticoagulation
• >12h since subq dose: manage anticoag as de novo

• sheath pull timing:

• ~4 hrs after 1 subq dose
• ~6 hrs after 2 subq doses
• ~8 hrs after >2 subq doses

Enoxaparin Percutaneous Coronary Intervention

• PCI:

• 1 dose subq enoxaparin <8h: 0.3 mg/kg IV
• >2 doses subq, last dose <8h: 0.1 mg/kg IV
• last subq enoxaparin 8-12h: 0.3 mg/kg IV
• >12h, or de novo:
• with GP IIb/IIIa: 0.5-0.6 mg/kg IV
• without GP IIb/IIIa: 0.75-1.0 mg/kg IV

• sheath pull timing (whichever is greater):

• IV enoxaparin only: ~4h after dose
• 1-2 doses of subq enoxaparin: ~6h after dose
• >3 doses of subq enoxaparin: ~8h after dose