NICE-3 National Investigators Collaborating on Enoxaparin
XXIInd Congress of the European Society of Cardiology
August 30, 2000
Amsterdam, The Netherlands
NICE-3 Objectives
To assess the safety profile (primarily with respect to bleeding) of enoxaparin and a IIb/IIIa antagonist (abciximab, eptifibatide or tirofiban) in patients with ACS
To assess the feasibility and safety of bringing patients to the cath laboratory on combination therapy (without the use of UFH)
NICE-3 Inclusion Criteria
Recent (w/in 24 hours) unprovoked or rest angina
Documented ischemic CAD
ECG changes
Abnormal biomarkers
Previously documented CAD
Patients on prior UFH could be included
NICE-3 Exclusion Criteria
Evolving Q-wave MI
Fibrinolytic Rx w/in 48 hours
Cardiogenic shock
Left main disease
Valvular disease
CABG w/in 2 mos.; revasc w/in 1 week
Thrombocytopenia
NICE-3 Protocol
Study Initiated January 2000
46 clinical sites in US/Canada
In-hospital, 14-day, and 30-day follow-up
661 patients enrolled
[Enoxaparin alone]
(n=45)
Data available August 2000
All IIb/IIIa patients
(n=616)
Enrollment Completed May 2000
If patients went to the cath lab, combination Rx continued; no UF heparin used
If within 8 hrs of last enoxaparin, no additional Rx
If > 8 hrs from last dose, 0.3 mg/kg enoxaparin iv
NICE-3 Protocol
Primary Endpoint
Non-CABG major bleeding (TIMI criteria)
during hospitalization
Secondary Endpoints
Minor bleeding (TIMI criteria)
Clinical efficacy
Composite of death, MI, ischemia-driven TVR
NICE-3 Sample Size
Primary Hypothesis
The 95% CI for major bleeding will not exceed the historical rate
Agents examined as a whole and separately
Example (Assuming major bleed rate of 2%):
A 200 patient sample size has a 95% CI of approx 0.1-3.9%
A 150 patient sample size has a 95% CI of approx 0-4.2%
NICE-3 Demographics
Age 62.9 ?12.2 years
Weight 83.9 ?18.5 kg
M/F approx 2:1
LOS 5.9 ? 4.2 days
History
HTN 63.5% Prior PCI 30.7%
DM 30.0% Prior CABG 20.9%
Smoking 28.1% Prior MI 36.2%
CHF (on admin) 4.5%
NICE-3 Bleeding (%)
Abciximab
(n=147)
Eptifibatide
(n=252)
Tirofiban
(n=217)
Enoxaparin
[Enoxaparin alone]
(n=45)
All IIb/IIIa
(n=616)
All 17.8
Major 6.7
non-CABG 4.4
Minor 13.3
Xfusion 8.9
All 27.2
Major 5.1
non-CABG 1.4
Minor 24.0
Xfusion 10.6
All 30.6
Major 4.4
non-CABG 3.2
Minor 27.2
Xfusion 10.3
All 24.5
Major 4.1
non-CABG 0.7
Minor 22.4
Xfusion 10.9
All 27.9
Major 4.5
non-CABG 1.9
Minor 25.0
Xfusion 10.5
NICE-3 In-Hospital Clinical Outcomes (%)
Abciximab
(n=147)
Eptifibatide
(n=252)
Tirofiban
(n=217)
[Enoxaparin alone]
(n=45)
All IIb/IIIa
(n=616)
Death 0
MI 2.2
uTVR 2.2
D/MI/uTVR 4.4
D/MI 2.2
Death 0.3
MI 3.4
uTVR 2.1
D/MI/uTVR 5.7
D/MI 3.6
Death 0.5
MI 4.1
uTVR 3.2
D/MI/uTVR 7.8
D/MI 4.6
Death 0.4
MI 3.2
uTVR 2.0
D/MI/uTVR 5.2
D/MI 3.2
Death 0
MI 2.7
uTVR 0.7
D/MI/uTVR 3.4
D/MI 2.7
Enoxaparin
NICE-3 ?30% ? in Platelet Count
0<100K
0.85%<100K
1.44%<100K
0.86%<100K
(n=138)
(n=235)
(n=208)
(n=581)
(n=38)
NICE-3 All Major Bleeding (%)
1
4.8
3.6
4.8
3.1
0.9
4.3
1.7
0
2
4
6
Abciximab
Eptifibatide
Tirofiban
All IIb/IIIa
Patients undergoing PCI
Patients not undergoing PCI or CABG
NICE-3 PCI Patients (n=292)
Tirofiban 0.9%
Eptifibatide 2.4%
Abciximab 0
All IIb/IIIa 1.0%
Non-CABG Major Bleeding
NICE-3 Conclusions
Combination of enoxaparin and IIb/IIIa
Does not result in excess major bleeding
Events (non-CABG)
Patients on combination Rx can safely undergo PCI
Clinical outcomes in NICE-3 were comparable to those noted in prior studies
Therefore, not necessary to use UFH in:
UA/NSTEMI patients undergoing coronary
intervention who are treated with enoxaparin and an IV IIb/IIIa antagonist