ISAR-REACT 2
One-year Clinical Outcomes in the ISARREACT 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
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
ESC 2007
ISAR-REACT 2
Presenter Disclosure Information
ISAR-REACT 2 Trial
Study performed without industry support
The following potential of conflict exist related to this presentation:
Seyfarth - Lecture fees from BMS, Lilly, Sanofi-Aventis: Modest level relationship
Kastrati - Lecture fees from BMS, Lilly, Sanofi-Aventis: Modest level relationship
Mehilli - No relationships to disclose
Neumann - No relationships to disclose
ten Berg - No relationships to disclose
Bruskina - No relationships to disclose
Dotzer - No relationships to disclose
Pache - No relationships to disclose
Dirschinger - No relationships to disclose
Berger - Lecture Fees from Schering Plough and from CME: Modest level relationship
Schömig - Unrestricted Grant from BMS and Nycomed: Modest level relationship
ESC 2007
ISAR-REACT 2
ISAR-REACT 2
Multicenter, randomized, double-blind, placebo-controlled trial
2022 patients with NSTE-ACS
Clopidogrel 600 mg at least 2h before procedure; Aspirin i.v.
Abciximab
 Heparin 70 U/Kg
 Abciximab (bolus & 12h infus.)
Placebo
 Heparin bolus of 140 U/Kg
 Placebo (bolus & 12h infus.)
Clopidogrel 2x75 mg/day until discharge
75 mg for at least 4 weeks
Aspirin 200 mg/day
ISAR-REACT 2, JAMA 2006
ESC 2007
ISAR-REACT 2
ISAR-REACT 2: Inclusion Criteria
• Rest anginal episodes in the last 48 hours
with
• An elevated troponin level (>.03 mg/L)
or
• ST-segment depression
ISAR-REACT 2, JAMA 2006
ESC 2007
ISAR-REACT 2
ISAR-REACT 2: Exclusion Criteria
• ST-elevation acute MI
• Hemodynamic instability
• Pericarditis
• Increased risk of bleeding, malignancies
• Relevant hematologic deviations
• Known allergic reaction to the study medication
• Pregnancy (present or suspected)
ISAR-REACT 2, JAMA 2006
ESC 2007
ISAR-REACT 2
ISAR-RACT 2: Primary End Point
A composite of death, MI or
urgent target vessel revascularization
within the first 30 days after PCI.
ISAR-REACT 2, JAMA 2006
ESC 2007
ISAR-REACT 2
Primary Endpoint of ISAR-REACT-2
Death/MI/TVR
15
Placebo
11.9
Abciximab
8.9
%
10
5
P=.03
RR 0.75 [0.58-0.97]
0
0
5
10
15
20
25
30
Days after randomization
ISAR-REACT 2, JAMA 2006
ESC 2007
ISAR-REACT 2
Objective of the present study
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.
ESC 2007
ISAR-REACT 2
Follow-Up Protocol
600 mg Clopidogrel
PCI
Abciximab vs. Placebo
0
serial CK
+ CKMB
measurements
30 d
6 mo
clinical
follow-up
clinical
follow-up
12 mo.
clinical
follow-up
ESC 2007
ISAR-REACT 2
Baseline Clinical Characteristics
Abciximab
n=1012
Placebo
n=1010
66.0±11.0
66.5±11.3
Women, %
Hypercholesterolemia, %
23.3
61.6
25.9
60.3
Arterial hypertension, %
Diabetes mellitus, %
62.5
24.9
64.3
28.1
Current smoker, %
Body mass index, kg/m2
22.7
21.7
Age, yrs
27.2 ±3.9
27.3±4.2
ESC 2007
ISAR-REACT 2
Baseline Clinical Characteristics (con‘t)
Abciximab
n=1012
Placebo
n=1010
53.3±12.3
53.3±12.5
Multivessel disease, %
Prior MI, %
74.4
24.2
74.3
24.1
Prior CABG, %
Elevated troponin, %
10.1
50.7
10.8
53.1
Ejection fraction, %
ESC 2007
ISAR-REACT 2
Lesion Characteristics
Abciximab
n=1012
Vessel
LCA, %
LAD, %
LCx, %
RCA, %
Bypass graft, %
Complex (B2/C) lesions, %
DES, %
BMS, %
PTCA, %
2.4
41.9
23.8
28.1
3.8
80.2
49.5
47.8
2.7
Placebo
n=1010
2.2
40.4
26.0
26.2
5.2
81.2
48.9
47.6
3.5
ESC 2007
ISAR-REACT 2
Primary Endpoint after 12 Months
- Survival free of MI and TVR 100
%
90
Abciximab
80
70
P=0.012
60
Placebo
RR 0.80 [0.67-0.95]
50
0
1
2
3
4
5
6
7
8
9
Months after randomization
10
11
12
ESC 2007
ISAR-REACT 2
Primary Endpoint after 12 Months
- Survival free of MI 100
%
Abciximab
90
80
Placebo
70
P=0.015
60
RR 0.74 [0.59-0.94]
50
0
1
2
3
4
5
6
7
8
9
Months after randomization
10
11
12
ESC 2007
ISAR-REACT 2
Subset Analyses
Abciximab
No./Total (%)
All Patients
Relative Risk
Placebo
No./Total (%)
234/1012 (23.3)
281/1010 (28.0)
128/482 (26.6)
106/530 (20.2)
159/527 (30.3)
122/483 (25.5)
51/236 (21.7)
183/776 (23.8)
71/262 (27.4)
210/748 (28.2)
68/252 (27.1)
166/760 (22.0)
80/284 (28.6)
201/726 (27.8)
146/513 (28.6)
88/499 (17.8)
178/536 (33.3)
103/474 (22.0)
93/475 (19.8)
141/537 (26.4)
115/461 (25.1)
166/549 (30.4)
Age
>67 years
≤67 years
Sex
Women
Men
Diabetes
Yes
No
Troponin >0.03 mg/L
Yes
No
Clopidogrel interval
>3 hours
≤3 hours
0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3
ESC 2007
ISAR-REACT 2
Troponin Level and Benefit With Abciximab
Death/MI/UTVR, %
20
Troponin-Positive: RR=0.71 [0.54-0.95]
15
10
Abciximab vs. Placebo
Troponin-Negative: RR=0.99 [0.56-1.76]
5
0
0
5
10
15
20
25
30
Days after randomization
ESC 2007
ISAR-REACT 2
Troponin Level and Benefit With Abciximab
after 12 Months
100
%
90
Troponin level ≤0.03 µg/L
80
P=0.10
70
P=0.07
Troponin level >0.03 µg/L
Abciximab
60
Placebo
50
0
1
2
3
4
5
6
7
8
9
Months after randomization
10
11
12
ESC 2007
ISAR-REACT 2
Efficacy Analysis
According to Troponin Level
Abciximab
Placebo
18
17.1
16.8
%
12.7
15.5
13.8
13.2
12
6.6 6.7
4.6 5.1
6
2.2 2.7
0
Death
MI
TVR
Troponin level >0.03 µg/L
Death
MI
TVR
Troponin level ≤0.03 µg/L
ESC 2007
ISAR-REACT 2
Conclusions
The early benefit of Abciximab in patients with NSTEACS 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.
ESC 2007