CRUSADE: NSTE ACS dosing of antithrombotics

1
CRUSADE NSTE ACS dosing of antithromboticsstudy
overview
Objective Investigate associations between
dosing of unfractionated heparin (UFH),
low-molecular- weight heparin (LMWH), and
glycoprotein (GP) IIb/IIIa inhibitors and major
clinical outcomes Design Prospective
observational analysis Population Registry
patients with NSTE ACS receiving antithrombotic
agents Primary outcome Relation between
excessive dosing of UFH, LMWH, and GP IIb/IIIa
inhibitors and major bleeding, in-hospital
mortality, and length of stay
NSTE ACS nonST segment elevation acute
coronary syndromes
Alexander KP et al. JAMA. 20052943108-16.
2
Major predictors of overdosing
Older age(65 years)
Renalinsufficiency
Patients vulnerable to overdosing
Alexander KP et al. JAMA. 20052943108-16.
3
Results Excess dosing by age
70
P lt 0.001 for all treatment groups
60
50
Excessdose()
40
30
20
10
0
UFH
LMWH
GP IIb/IIIa inhibitors
Patient age (years)
lt65
75
6574
Alexander KP et al. JAMA. 20052943108-16.
4
Results Antithrombotic therapy dose and major
bleeding
35
Underdosed
Recommended
Mild excess
Major excess
30
25
P lt 0.001
P 0.25
P lt 0.001
Majorbleeding()
20
15
10
5
0
n 714
n 922
n 237
n 178
n 2074
n 2063
n 2073
n 2327
n 3998
n 5879
n 1955
UFH
LMWH
GP IIb/IIIa inhibitors
Data are for noncoronary bypass grafting and
nontransfer population
Alexander KP et al. JAMA. 20052943108-16.
5
Recommended dosing of antithrombotic agents
Drug Recommended dose Dosing adjustments
UFH Bolus 6070 U/kg and infusion 1215 U/kg per h Patients gt60 y may require lower doses
LMWH Enoxaparin 1 mg/kg SC every 12 h ? dose by 50 by increasing interval to every 24 h if CrCl lt30 mL/min
GP IIb/IIIa inhibitor Eptifibatide Bolus 180 µg/kg and infusion 2 µg/kg per min ? infusion by 50 to 1 µg/kg per min if CrCl 50 mL/min or serum creatinine 24 mg/dL
GP IIb/IIIa inhibitor Tirofiban Bolus 0.4 µg/kg per min and infusion 0.1 µg/kg per min ? bolus and infusion by 50 to0.05 µg/kg per min if CrCl 30 mL/min
Alexander KP et al. JAMA. 20052943108-16.
6
Clinical implications

• Early use of antithrombotic agents plays a key
  role in management of NSTE ACS, but dosing
  errors are common
• Dosing errors occur more often in elderly and
  others already vulnerable to bleeding
• Dosing errors predict an increased risk of major
  bleeding
• Altering dosing based on weight and renal
  function minimizes bleeding while preserving
  therapeutic benefit
• Patients receiving recommended doses of heparin
  and GP IIb/IIIa inhibitors alone or in
  combination have the lowest rates of bleeding

Proper dosing of antithrombotic therapies is
necessary to prevent bleeding complications in
vulnerable patients
Alexander KP et al. JAMA. 20052943108-16.