presenter disclosure information isar-react 2 trial

ISAR-REACT 2ISAR-REACT 2

ESC 2007

M. Seyfarth, A. Kastrati, J. Mehilli, F.-J. Neumann, J. ten Berg, O. Bruskina, F. Dotzer, J. Pache,

J. Dirschinger, P. B. Berger, A. Schömig

One-year Clinical Outcomes in the ISAR-REACT 2 Trial, a Randomized Comparison of Abciximab Versus Placebo in Patients With non-ST Segment Elevation Acute Coronary

Syndromes Undergoing PCI After Pretreatment With Clopidogrel


ESC 2007

Seyfarth - Lecture fees from BMS, Lilly, Sanofi-Aventis: Modest level relationshipKastrati - Lecture fees from BMS, Lilly, Sanofi-Aventis: Modest level relationshipMehilli - No relationships to discloseNeumann - No relationships to discloseten Berg - No relationships to discloseBruskina - No relationships to disclose Dotzer - No relationships to disclose Pache - No relationships to disclose Dirschinger - No relationships to discloseBerger - Lecture Fees from Schering Plough and from CME: Modest level relationshipSchömig - Unrestricted Grant from BMS and Nycomed: Modest level relationship

Presenter Disclosure InformationISAR-REACT 2 Trial

The following potential of conflict exist related to this presentation:

Study performed without industry support


ESC 2007

2022 patients with NSTE-ACSClopidogrel 600 mg at least 2h before procedure; Aspirin i.v.

Heparin 70 U/KgHeparin 70 U/Kg Abciximab (bolus & 12h infus.)Abciximab (bolus & 12h infus.)

Heparin bolus of 140 U/KgHeparin bolus of 140 U/Kg Placebo (bolus & 12h infus.)Placebo (bolus & 12h infus.)

Clopidogrel 2x75 mg/day until discharge 75 mg for at least 4 weeks

Aspirin 200 mg/day

ISAR-REACT 2Multicenter, randomized, double-blind, placebo-controlled trial

PlaceboAbciximab

ISAR-REACT 2, JAMA 2006


ESC 2007

ISAR-REACT 2: Inclusion Criteria

• Rest anginal episodes in the last 48 hoursRest anginal episodes in the last 48 hourswithwith

• An elevated troponin level (>.03 An elevated troponin level (>.03 g/L)g/L)oror

• ST-segment depressionST-segment depression



ESC 2007

ISAR-REACT 2: Exclusion Criteria

• ST-elevation acute MIST-elevation acute MI

• Hemodynamic instabilityHemodynamic instability

• PericarditisPericarditis

• Increased risk of bleeding, malignanciesIncreased risk of bleeding, malignancies

• Relevant hematologic deviationsRelevant hematologic deviations

• Known allergic reaction to the study medicationKnown allergic reaction to the study medication

• Pregnancy (present or suspected)Pregnancy (present or suspected)



ESC 2007

ISAR-RACT 2: Primary End Point

A composite of death, MI or A composite of death, MI or urgent target vessel revascularization urgent target vessel revascularization

within the first 30 days after PCI.within the first 30 days after PCI.



ESC 2007

Primary Endpoint of ISAR-REACT-2

Death/MI/TVR

P=.03

RR 0.75 [0.58-0.97]

Abciximab

11.9

8.9

0

5

10

15

0 5 10 15 20 25 30

Days after randomization

% Placebo



ESC 2007

to investigate whether benefits of abciximab are maintained at 1 year

after PCI in patients with NSTE-ACS enrolled in the ISAR-REACT 2 trial.

Objective of the present study


ESC 2007

serial CK+ CKMB

measurements

600 mg Clopidogrel

PCIAbciximab vs. Placebo

0

clinicalfollow-up

12 mo.

Follow-Up Protocol

30 d

clinicalfollow-up

6 mo

clinicalfollow-up


ESC 2007

Abciximabn=1012

Placebon=1010

Age, yrs 66.0±11.0 66.5± 11.3

Women, % 23.3 25.9

Hypercholesterolemia, % 61.6 60.3

Arterial hypertension, % 62.5 64.3

Current smoker, % 22.7 21.7

Diabetes mellitus, % 24.9 28.1

Body mass index, kg/m2 27.2±3.9 27.3±4.2

Baseline Clinical Characteristics


ESC 2007

Abciximabn=1012

Placebon=1010

Ejection fraction, % 53.3±12.3 53.3±12.5

Multivessel disease, % 74.4 74.3

Prior MI, % 24.2 24.1

Prior CABG, % 10.1 10.8

Elevated troponin, % 50.7 53.1

Baseline Clinical Characteristics (con‘t)


ESC 2007

Abciximabn=1012

Placebon=1010

VesselLCA, % 2.4 2.2LAD, % 41.9 40.4LCx, % 23.8 26.0RCA, % 28.1 26.2Bypass graft, % 3.8 5.2

Complex (B2/C) lesions, % 80.2 81.2DES, % 49.5 48.9BMS, % 47.8 47.6PTCA, % 2.7 3.5

Lesion Characteristics


ESC 2007

Primary Endpoint after 12 Months- Survival free of MI and TVR -

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10 11 12

P=0.012

RR 0.80 [0.67-0.95]

Abciximab

Months after randomization

Placebo

%


ESC 2007

Primary Endpoint after 12 Months- Survival free of MI -

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10 11 12

P=0.015

RR 0.74 [0.59-0.94]

Abciximab


Placebo

%


ESC 20070.5 0.6 0.7 0.8 0.9 1.0

All Patients 234/1012 (23.3) 281/1010 (28.0)

>67 years 128/482 (26.6) 159/527 (30.3)

≤67 years 106/530 (20.2) 122/483 (25.5)

Women 51/236 (21.7) 71/262 (27.4)

Men 183/776 (23.8) 210/748 (28.2)

Yes 68/252 (27.1) 80/284 (28.6)

No 166/760 (22.0) 201/726 (27.8)

Yes 146/513 (28.6) 178/536 (33.3)

No 88/499 (17.8) 103/474 (22.0)

>3 hours 93/475 (19.8) 115/461 (25.1)

≤3 hours 141/537 (26.4) 166/549 (30.4)

Age

Sex

Diabetes

Troponin >0.03 g/L

Clopidogrel interval

1.1 1.2 1.3

AbciximabNo./Total (%)

Relative RiskPlacebo

No./Total (%)

Subset Analyses


ESC 2007

0

5

10

15

20

0 5 10 15 20 25 30Days after randomization

Death/MI/UTVR, %

Troponin Level and Benefit With Abciximab

Abciximab vs. Placebo

Troponin-Positive: RR=0.71 [0.54-0.95]

Troponin-Negative: RR=0.99 [0.56-1.76]


ESC 2007

Troponin Level and Benefit With Abciximabafter 12 Months

50

60

70

80

90

100

0 1 2 3 4 5 6 7 8 9 10 11 12

Abciximab


Placebo

%

Troponin level >0.03 µg/L

P=0.07

Troponin level ≤0.03 µg/L

P=0.10


ESC 2007

6.6 6.7

0

6

12

18

Death MI TVR

%

Abciximab

Placebo

Efficacy AnalysisAccording to Troponin Level

12.7

16.8

13.815.5

2.2 2.7

Death MI TVR

4.6 5.1

13.2

17.1

Troponin level ≤0.03 µg/L Troponin level >0.03 µg/L


ESC 2007

The early benefit of Abciximab in patients with NSTE-

ACS undergoing PCI after pretreatment with 600 mg

Clopidogrel is maintained at 1 year after administration.

Another novel finding of this 1-year analysis is the

additional benefit of Abciximab in low-risk patients

without an elevated troponin in terms of a reduction

of target vessel revascularization.

Conclusions

presenter disclosure information isar-react 2 trial

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