ISARREACT 2 - PowerPoint PPT Presentation

Title: ISARREACT 2


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ISAR-REACT 2

• Peter B Berger MD
• Professor of Medicine
• Director of Interventional Cardiology
• Duke University Medical Center and DCRI
• March 2006

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Potential conflicts (five years)

• Unrestricted educational grants for Dukes
  televised cath lab conference sanofi-aventis,
  Lilly/Sankyo, Datascope, Medtronic, Cordis/JJ,
  The Medicine Co.
• Research support Conor, Guilford
• Scientific advisory boards Cordis/JJ,
  Genentech, Guilford, Boston Scientific
• Honoraria from symposia BMS, sanofi-aventis,
  Guilford, Schering-Plough
• Equity Lumen, Inc.

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ISAR-REACT
Patients undergoingstent placementn2159
Clopidogrel 600 mg gt2 hours pre-PCI
1 end point Death, MI, TVR at 30 days
Kastrati A et al NEJM 2004350232-8.
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ISAR-REACT Exclusion criteria

• Acute coronary syndrome with gt1 mm ST-segment
  shift at rest, elevated biomarkers
• Recent MI (lt14 days)
• Insulin-dependent diabetes mellitus
• (NIDDM patients comprised 20 of patients)

Kastrati A et al NEJM 2004350232-8.
5
ISAR-REACTBaseline characteristics
Abciximab n1079
Placebo n1080
Diabetes mellitus,
21
20
Multilesion PCI,
75
75
Lesions dilated 1401 1410
Prior MI,
32
33
Prior CABG,
10
9
Angina class III or IV,
40
40
Kastrati A et al NEJM 2004350232-8.
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ISAR-REACTResults, 30 days
Event rate ()
Death , Death Q MI Non-Q MI
TVR MI, TVR
Kastrati A et al NEJM 2004350232-8.
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ISAR-REACT MACE at 30 days
Odds Abciximab ratio Placebo
No. No. All 45/1079 4.2 43/1080 4.0 Age
gt70 year 20/377 5.3 17/404 4.2 ?70
year 25/702 3.6 26/676 3.8 Gender
Men 37/826 4.5 35/824 4.2 Women 8/253 3.2 8/25
6 3.1 Diabetes Yes 11/227 4.8 11/214 5.1
No 34/852 4.0 32/866 3.7 Angina class ?III or
prior MI Yes 28/647 4.3 30/653 4.6
No 17/432 3.9 13/427 3.0 Intervention in complex
lesions Yes 36/735 4.9 30/751 4.0
No 9/344 2.6 13/329 3.9
Abciximab better
Placebo better
Berger ACC2006
Kastrati A et al NEJM 2004350232-8.
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ISAR-REACT Death or MI,12 months
10
p0.73
8
6.0
4.0
6
Death/MI,
6.4
4
Abciximab
4.5
2
Placebo
0
0
1
2
3
4
5
6
7
8
9
10
11
12
Months after randomization
Berger ACC2006
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ISAR-SMART 2
Small vessels lt2.5 mmn502
Clopidogrel 600 mg gt2 hours pre-PCI
Hausleiter J Int Med 200425638897
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ISAR-SMART 2Survival free of MI
Placebo n251
93.1
91.2
Abciximab n251
Survival ()
p0.40
Days after PCI
Hausleiter J Int Med 200425638897
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ISAR-SWEET
Planned stent placement IDDM or NIDDMn670
Clopidogrel 600 mg gt2 hours pre-PCI
1 endpoint Death, MI, TVR at 30 days
Angiographic restenosis
Kastrati A et al Circulation 20041103627-35
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ISAR-SWEETOne-year adverse events
All pNS
Adverse events ()
Abciximab n335
Placebo n335
Kastrati A et al Circulation 20041103627-35
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ISAR-SWEET Death /MI at 12 months in
insulin-treated patients
p0.66 Risk reduction 15
Death/MI
Death/MI ()
Abciximab n101
Placebo n99
Kastrati A et al Circulation 20041103627-35
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ISAR-REACT 2 (Intracoronary Stenting and
Antithrombotic Regimen-Rapid Early Action for
Coronary Treatment) A prospective, randomized,
double-blind, placebo-controlled trial of GP
IIb/IIIa inhibition with abciximab in patients
with ACS undergoing stenting after pretreatment
with a high loading dose of clopidogrel
A Kastrati, J Mehilli, F-J Neumann, F Dotzer,
JM ten Berg, H Bollwein, C Vollmer, J
Dirschinger, P Berger, A Schömig
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ISAR-REACT 2
Planned stent placement ACS with ? biomarker or
ST segment shiftsn2022
Clopidogrel 600 mg gt2 hours pre-PCI
Kastrati A et al. JAMA 20062951531-38
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ISAR-REACT 2
Aspirin Clopidogrel 600 mg gt2 hours before the
procedure Heparin 70 U/kg bolus
Placebo group
Abciximab group
No additional heparin Abciximab bolus of 0.25
mg/kg Infusion of 0.125 µg/kg/min for 12h
Heparin - additional 70 U/kg bolus Placebo
infusion for 12h
Clopidogrel 2 x 75 mg/day until discharge 75 mg
for at least 4 weeks Aspirin 200 mg/day
Kastrati A et al. JAMA 20062951531-38
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ISAR-REACT 2

• Inclusion criteria
• Rest anginal episodes in the last 48 hours
• and either
• An elevated troponin level (gt0.03 µg/L)
• or
• ST-segment depression

Kastrati A et al. JAMA 20062951531-38
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ISAR-REACT 2

• Exclusion criteria
• ST-elevation acute MI
• Hemodynamic instability
• Pericarditis
• Increased risk of bleeding, malignancies, and
  pericarditis
• Relevant hematologic abnormalities
• Known allergic reaction to a study medication
• Pregnancy (present or suspected)

Kastrati A et al. JAMA 20062951531-38
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ISAR-REACT 2Primary efficacy endpoint

• A composite of death, MI, or urgent target
  vessel revascularization within the first 30
  days after PCI

Kastrati A et al. JAMA 20062951531-38
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ISAR-REACT 2Safety analysis In-hospital

• Major and minor bleeding complications (TIMI
  criteria)
• Profound thrombocytopenia (lt20 000 plt/mm3)
• Need for blood transfusions

Kastrati A et al. JAMA 20062951531-38
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ISAR-REACT 2 Sample size estimation

• Incidence of 1o end point with placebo 12
• Incidence of 1o end point with abciximab 8 (a
  33 reduction with abciximab)
• ?-level 5
• Power 80
• Required 1800 patients

Kastrati A et al. JAMA 20062951531-38
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ISAR-REACT 2Baseline characteristics
Abciximab n1012
Placebo n1010
Age, years
66.0

11.0
66.5

11.3
Women,
23.3
25.9
Hypercholesterolemia,
61.6
60.3
Arterial hypertension,
62.5
64.3
Diabetes mellitus,
24.9
28.1
Current smoker,
22.7
21.7
Body mass index, kg/m2
27.2

3.9
27.3

4.2
Kastrati A et al. JAMA 20062951531-38
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ISAR-REACT 2Baseline characteristics
Abciximab n1012 ()
Placebo n1010 ()
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
Kastrati A et al. JAMA 20062951531-38
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ISAR-REACT 2Lesion characteristics
Abciximab n1012 ()
Placebo n1010 ()
Vessel
LCA
2.4
2.2
LAD
41.9
40.4
LCx
23.8
26.0
RCA
28.1
26.2
Bypass graft
3.8
5.2
Complex (B2/C) lesions
80.2
81.2
DES
49.5
48.9
BMS
47.8
47.6
PTCA
2.7
3.5
Kastrati A et al. JAMA 20062951531-38
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ISAR-REACT 2Safety analysis
p0.29
p0.46
p0.008
pgt0.99

Kastrati A et al. JAMA 20062951531-38
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ISAR-REACT 2Efficacy analysis
p0.03
p0.06
-25
-25

p0.33
p0.66
-31
-17
Kastrati A et al. JAMA 20062951531-38
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ISAR-REACT 2 1o end point
Death/MI/UTVR,
15
11.9
8.9
10
Abciximab vs Placebo
5
RR 0.75 95 CI, 0.58-0.97
0
5
10
15
20
25
30
0
Days after randomization
Berger ACC2006
Kastrati A et al. JAMA 20062951531-38
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ISAR-REACT 2 Subgroup analysis
Abciximab No./Total ()
Placebo No./Total ()
Relative risk
90/1012 (8.9)
120/1010 (11.9)
All
Troponin
gt0.03 µg/L
67/513 (13.1)
98/536 (18.3)
23/499 (4.6)
22/474 (4.6)
0.03 µg/L
Clopidogrel pretreatment Duration
gt3 hours
27/475 (5.7)
35/461 (7.6)
63/537 (11.7)
85/549 (15.5)
2-3 hours
Diabetes
Yes
26/252 (10.3)
32/284 (11.3)
64/760 (8.4)
88/726 (12.1)
No
1
0.4
2
Kastrati A et al. JAMA 20062951531-38
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Troponin level and benefit with abciximab
Death/MI/UTVR,
20
Troponin-positive RR0.71 0.54-0.95
15
Abciximab vs Placebo
10
Troponin-negative RR0.99 0.56-1.76
5
0
0
5
10
15
20
25
30
Days after randomization
Berger ACC2006
Kastrati A et al. JAMA 20062951531-38
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Combined analysis of ISAR trials evaluating
abciximab in addition to clopidogrel post-PCI
Troponin-negative patients only
Estimated odds ratio 1.05 1.35 1.66 0.99 1.14
Trial ISAR-REACT ISAR-SWEET ISAR-SMART
2 ISAR-REACT 2 (t -) Combined
N 2159 701 502 973 4335
0
1
2
3
4
Abciximab worse
Abciximab better
Courtesy S Steinhubl, MD
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ISAR-REACT 2Conclusions

• Abciximab reduces the risk of adverse events in
  high-risk patients with non-ST-segment elevation
  ACS undergoing PCI after pretreatment with 600 mg
  of clopidogrel.
• The benefits provided by abciximab appear to be
  confined to patients presenting with an elevated
  troponin level.