1. ISAR-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

2. ISAR-REACT 2 ESC 2007 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 Presenter Disclosure Information ISAR-REACT 2 Trial The following potential of conflict exist related to this presentation: Study performed without industry support

3. ISAR-REACT 2 ESC 2007 2022 patients with NSTE-ACS Clopidogrel 600 mg at least 2h before procedure; Aspirin i.v.  Heparin 70 U/Kg  Abciximab (bolus & 12h infus.)  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 Multicenter, randomized, double-blind, placebo-controlled trial PlaceboAbciximab ISAR-REACT 2, JAMA 2006

4. ISAR-REACT 2 ESC 2007 ISAR-REACT 2: Inclusion Criteria Rest anginal episodes in the last 48 hours withRest anginal episodes in the last 48 hours with An elevated troponin level (>.03  g/L) orAn elevated troponin level (>.03  g/L) or ST-segment depressionST-segment depression ISAR-REACT 2, JAMA 2006

5. ISAR-REACT 2 ESC 2007 ISAR-REACT 2: Exclusion Criteria ST-elevation acute MI ST-elevation acute MI Hemodynamic instability Hemodynamic instability Pericarditis Pericarditis Increased risk of bleeding, malignancies Increased risk of bleeding, malignancies Relevant hematologic deviations Relevant hematologic deviations Known allergic reaction to the study medication Known allergic reaction to the study medication Pregnancy (present or suspected) Pregnancy (present or suspected) ISAR-REACT 2, JAMA 2006

6. ISAR-REACT 2 ESC 2007 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

7. ISAR-REACT 2 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 051015202530 Days after randomization % Placebo ISAR-REACT 2, JAMA 2006

8. ISAR-REACT 2 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

9. ISAR-REACT 2 ESC 2007 serial CK + CKMB measurements 600 mg Clopidogrel PCI Abciximab vs. Placebo 0 clinical follow-up 12 mo. Follow-Up Protocol 30 d clinical follow-up 6 mo clinical follow-up

10. ISAR-REACT 2 ESC 2007 Abciximab n=1012 Placebo n=1010 Age, yrs66.0±11.066.5± 11.3 Women, %23.325.9 Hypercholesterolemia, %61.660.3 Arterial hypertension, %62.564.3 Current smoker, %22.721.7 Diabetes mellitus, %24.928.1 Body mass index, kg/m 2 27.2±3.927.3±4.2 Baseline Clinical Characteristics

11. ISAR-REACT 2 ESC 2007 Abciximab n=1012 Placebo n=1010 Ejection fraction, %53.3±12.353.3±12.5 Multivessel disease, %74.474.3 Prior MI, %24.224.1 Prior CABG, %10.110.8 Elevated troponin, %50.753.1 Baseline Clinical Characteristics (con‘t)

12. ISAR-REACT 2 ESC 2007 Abciximab n=1012 Placebo n=1010 Vessel LCA, %2.42.2 LAD, %41.940.4 LCx, %23.826.0 RCA, %28.126.2 Bypass graft, % 3.85.2 Complex (B2/C) lesions, % 80.281.2 DES, % 49.548.9 BMS, %47.847.6 PTCA, %2.73.5 Lesion Characteristics

13. ISAR-REACT 2 ESC 2007 Primary Endpoint after 12 Months - Survival free of MI and TVR - 50 60 70 80 90 100 0123456789101112 P=0.012 RR 0.80 [0.67-0.95] Abciximab Months after randomization Placebo %

14. ISAR-REACT 2 ESC 2007 Primary Endpoint after 12 Months - Survival free of MI - 50 60 70 80 90 100 0123456789101112 P=0.015 RR 0.74 [0.59-0.94] Abciximab Months after randomization Placebo %

15. ISAR-REACT 2 ESC 2007 0.5 0.60.70.8 0.91.0 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) Women51/236 (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 1.11.2 1.3 Abciximab No./Total (%) Relative Risk Placebo No./Total (%) Subset Analyses

16. ISAR-REACT 2 ESC 2007 0 5 10 15 20 051015202530 Days 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]

17. ISAR-REACT 2 ESC 2007 Troponin Level and Benefit With Abciximab after 12 Months 50 60 70 80 90 100 0123456789101112 Abciximab Months after randomization Placebo % Troponin level >0.03 µg/L P=0.07 Troponin level ≤0.03 µg/L P=0.10

18. ISAR-REACT 2 ESC 2007 6.6 6.7 0 6 12 18 DeathMITVR % Abciximab Placebo Efficacy Analysis According to Troponin Level 12.7 16.8 13.8 15.5 2.2 2.7 DeathMITVR 4.6 5.1 13.2 17.1 Troponin level ≤0.03 µg/LTroponin level >0.03 µg/L

19. ISAR-REACT 2 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