nice-3 n ational i nvestigators c ollaborating on e noxaparin

NICE-3NICE-3NNational ational IInvestigators nvestigators CCollaborating on ollaborating on

EEnoxaparinnoxaparin

NICE-3NICE-3NNational ational IInvestigators nvestigators CCollaborating on ollaborating on

EEnoxaparinnoxaparin

XXIIXXIIndnd Congress of the European Congress of the European Society of CardiologySociety of Cardiology

August 30, 2000August 30, 2000

Amsterdam, The NetherlandsAmsterdam, The Netherlands

XXIIXXIIndnd Congress of the European Congress of the European Society of CardiologySociety of Cardiology

August 30, 2000August 30, 2000

Amsterdam, The NetherlandsAmsterdam, The Netherlands

2

NICE-3 ObjectivesNICE-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)

• 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)

3

NICE-3 Inclusion Criteria

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

• 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

4

NICE-3 Exclusion Criteria

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

• 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

5

NICE-3ProtocolNICE-3Protocol

Study Study Initiated Initiated

January 2000January 2000

46 clinical sites 46 clinical sites in US/Canadain US/Canada

In-hospital, 14-day, In-hospital, 14-day, and 30-day follow-and 30-day follow-

upup

661 patients 661 patients enrolledenrolled

[Enoxaparin [Enoxaparin alone]alone]

(n=45)(n=45)

Data Data available available

August 2000August 2000

All IIb/IIIa patientsAll IIb/IIIa patients(n=616)(n=616)

Enrollment Enrollment Completed May Completed May

20002000

AbciximabAbciximab

(n=147)(n=147)

EptifibatideEptifibatide

(n=252)(n=252)

TirofibanTirofiban

(n=217)(n=217)

All treated All treated with with

EnoxaparinEnoxaparin

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

6

NICE-3ProtocolNICE-3Protocol

• 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

• 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

7

NICE-3Sample Size

NICE-3Sample 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%

• 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%

8

NICE-3Demographics

NICE-3Demographics

AgeAge 62.9 62.9 12.2 years12.2 years

WeightWeight 83.9 83.9 18.5 kg18.5 kg

M/F M/F approx 2:1approx 2:1

LOSLOS 5.9 5.9 4.2 days 4.2 days

AgeAge 62.9 62.9 12.2 years12.2 years

WeightWeight 83.9 83.9 18.5 kg18.5 kg

M/F M/F approx 2:1approx 2:1

LOSLOS 5.9 5.9 4.2 days 4.2 days

HistoryHistory

HTNHTN 63.5%63.5% Prior PCIPrior PCI 30.7%30.7%

DMDM 30.0%30.0% Prior CABGPrior CABG 20.9%20.9%

SmokingSmoking 28.1%28.1% Prior MIPrior MI 36.2%36.2%

CHF (on admin) 4.5%CHF (on admin) 4.5%

9

NICE-3Bleeding (%)

NICE-3Bleeding (%)

AbciximabAbciximab

(n=147)(n=147)


(n=252)(n=252)

TirofibanTirofiban

(n=217)(n=217)

EnoxapariEnoxaparinn

[Enoxaparin [Enoxaparin alone]alone]

(n=45)(n=45)

All All IIb/IIIaIIb/IIIa

(n=616)(n=616)

AllAll 17.817.8

Major Major 6.76.7

non-CABGnon-CABG

4.4 4.4

MinorMinor 13.313.3

XfusionXfusion 8.98.9

AllAll 27.227.2

Major Major 5.15.1

non-CABGnon-CABG

1.4 1.4

MinorMinor 24.024.0


AllAll 30.630.6

Major Major 4.44.4

non-CABGnon-CABG

3.2 3.2

MinorMinor 27.227.2


AllAll 24.524.5

Major Major 4.14.1

non-CABGnon-CABG

0.70.7

MinorMinor 22.422.4


AllAll 27.9 27.9

Major Major 4.5 4.5

non-CABG 1.9non-CABG 1.9

MinorMinor 25.0 25.0

XfusionXfusion 10.5 10.5

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NICE-3In-Hospital Clinical Outcomes

(%)

NICE-3In-Hospital Clinical Outcomes

(%)

AbciximabAbciximab

(n=147)(n=147)


(n=252)(n=252)

TirofibanTirofiban

(n=217)(n=217)

[Enoxaparin [Enoxaparin alone]alone](n=45)(n=45)

All IIb/IIIaAll IIb/IIIa

(n=616)(n=616)

DeathDeath 0 0

MI MI 2.2 2.2

uTVRuTVR 2.2 2.2

D/MI/uTVR 4.4D/MI/uTVR 4.4

D/MID/MI 2.2 2.2

DeathDeath 0.30.3

MI MI 3.43.4

uTVRuTVR 2.1 2.1


D/MID/MI 3.63.6

DeathDeath 0.5 0.5

MI MI 4.1 4.1

uTVRuTVR 3.2 3.2


D/MID/MI 4.6 4.6

DeathDeath 0.40.4

MI MI 3.23.2

uTVRuTVR 2.0 2.0


D/MID/MI 3.23.2

DeathDeath 0 0

MI MI 2.7 2.7

uTVRuTVR 0.7 0.7


D/MID/MI 2.7 2.7

EnoxapariEnoxaparinn

11

NICE-330% in Platelet Count

NICE-330% in Platelet Count

9.4

4.7

3.8

5.5

00

2

4

6

8

10

Abciximab Eptifibatide Tirofiban All I Ib/ I I Ia No I Ib/ I I Ia

9.4

4.7

3.8

5.5

00

2

4

6

8

10

Abciximab Eptifibatide Tirofiban All I Ib/ I I Ia No I Ib/ I I Ia

0<100K 0.85%<100K 1.44%<100K 0.86%<100K

(n=138)(n=138) (n=235)(n=235) (n=208)(n=208) (n=581)(n=581) (n=38)(n=38)

12

NICE-3All Major Bleeding (%)

NICE-3All 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 PCIPatients undergoing PCI Patients not undergoing PCI or CABG

Patients not undergoing PCI or CABG

13

NICE-3PCI Patients (n=292)

NICE-3PCI Patients (n=292)

Tirofiban 0.9%

Eptifibatide2.4%

Abciximab 0

All IIb/IIIa1.0%

Tirofiban 0.9%

Eptifibatide2.4%

Abciximab 0

All IIb/IIIa1.0%

Non-CABG Major BleedingNon-CABG Major Bleeding

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NICE-3Conclusions

NICE-3Conclusions

• 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

• 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

nice-3 n ational i nvestigators c ollaborating on e noxaparin

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