Transcript VBWG06-CRUSADE (6 slides

CRUSADE: NSTE ACS dosing of
antithrombotics—study overview
VBWG
Objective:
Investigate associations between dosing of
unfractionated heparin (UFH), low-molecularweight 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 = non–ST segment elevation
acute coronary syndromes
Alexander KP et al. JAMA. 2005;294:3108-16.
VBWG
Major predictors of overdosing
Older age
(≥65 years)
Renal
insufficiency
Female
Patients
vulnerable to
overdosing
Low body
weight
Diabetes
CHF
Alexander KP et al. JAMA. 2005;294:3108-16.
VBWG
Results: Excess dosing by age
70
P < 0.001 for all treatment groups
60
50
Excess
dose
(%)
40
30
20
10
0
UFH
Patient age (years)
LMWH
<65
65–74
GP IIb/IIIa inhibitors
≥75
Alexander KP et al. JAMA. 2005;294:3108-16.
VBWG
Results: Antithrombotic therapy dose
and major bleeding
35
Underdosed
Recommended
Mild excess
Major excess
30
25
Major
bleeding
(%)
P < 0.001
P = 0.25
P < 0.001
20
15
10
5
0
UFH
Data are for non–coronary bypass grafting
and nontransfer population
LMWH
GP IIb/IIIa inhibitors
Alexander KP et al. JAMA. 2005;294:3108-16.
Recommended dosing of antithrombotic
agents
Drug
Recommended dose
Dosing adjustments
UFH
Bolus 60–70 U/kg and
infusion 12–15 U/kg per h
Patients >60 y may require
lower doses
LMWH:
Enoxaparin
1 mg/kg SC every 12 h
 dose by 50% by increasing
GP IIb/IIIa
inhibitor:
Eptifibatide
Bolus 180 µg/kg and
infusion 2 µg/kg per min
GP IIb/IIIa
inhibitor:
Tirofiban
Bolus 0.4 µg/kg per min and  bolus and infusion by 50% to
infusion 0.1 µg/kg per min
0.05 µg/kg per min if CrCl
≤30 mL/min
VBWG
interval to every 24 h if CrCl
<30 mL/min
 infusion by 50% to 1 µg/kg per min
if CrCl ≤50 mL/min or serum
creatinine = 2–4 mg/dL
Alexander KP et al. JAMA. 2005;294:3108-16.
VBWG
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. 2005:294:3108-16.