1. Enoxaparin in primary PCI From FINESSE to ATOLL G. Montalescot Institut de Cardiologie Pitié-Salpêtrière Hospital Paris, France The FINESSE Trial is supported by Eli Lilly and Co and Centocor. G. Montalescot, disclosure: Institutional research grant, consulting and speaker fees from Daiichi Sankyo, Eli Lilly, Sanofi Aventis, BMS.

2. Procedure- and Non-Procedure-Related Bleeds Associated With Increased 30-Day Mortality in NSTE ACS Procedure-related GUSTO bleeds Non-procedure-related GUSTO bleeds Risk of death (HR) None 1.0 Mild 1.3 Severe 16.5 0 5 20 10 15 None 1.0 Mild 2.1 Moderate 2.5 Severe 10.9 Moderate 3.7 Rao SV, et al. Am J Cardiol. 2005;96:1200-1206.

3. Can we improve safety in PCI with enoxaparin?

4. STEEPLE Non-CABG-Related Bleeding* P = 0.01 P = 0.051 P = 0.004 P = 0.007 -57% *1° endpoint Montalescot G, et al. N Engl J Med. 2006;355:1006-1017.

5. 0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 051015202530 0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 051015202530 0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 051015202530 Nonfatal MIDeathUTVR Enoxaparin 0.5 mg/kgEnoxaparin 0.75 mg/kg UFH P = all NS STEEPLE Individual Ischemic Endpoints at 30 Days Days Montalescot G, et al. N Engl J Med. 2006;355:1006-1017.

6. Meta-Analysis: IV LMWH in PCI (N = 7,318; 13 Studies) LMWH better UFH better Major bleeding Death MI Death or MI Composite efficacy 0123 P = 0.002 Dumaine R, et al. Arch Intern Med. 2007;167:2423-2430.

7. FINESSE: Improved Safety and Efficacy in Facilitated PCI UFH (40 U/kg, 3,000 U max) “Main Study” (N = 1,693) Enoxaparin (0.5 mg/kg IV, 0.3 mg/kg SC) “LMWH Substudy” (N = 759) R Reteplase/abciximab- facilitated 1 ° PCI (n = 258) Abciximab-facilitated 1 ° PCI (n = 255) 1 ° PCI w/ in-lab abciximab (n = 246) Reteplase/abciximab- facilitated 1 ° PCI (n = 570) Abciximab-facilitated 1 ° PCI (n = 563) 1 ° PCI w/ in-lab abciximab (n = 560) R Montalescot G. TCT 2007.

8. FINESSE: TIMI Major Bleeding 0 5 10 15 1° UFH 1° LMWH Abx Fac UFH Abx Fac LMWH Ret/Abx Fac UFH Ret/Abx Fac LMWH All UFH All LMWH Major bleeding (%) Montalescot G. TCT 2007. 2.9 2.5 1.6 5.7 4.4 5.2 P = 0.043 P = 0.464 P = 0.015 P = NS 2.9 4.6

9. Can we improve safety and efficacy in primary PCI?

10. FINESSE: Death, ReMI, Urgent Revasc, or Refractory Ischemia Through Day 30 Montalescot G. TCT 2007. 0 5 10 15 1° UFH 1° LMWH Abx Fac UFH Abx Fac LMWH Ret/Abx Fac UFH Ret/Abx Fac LMWH All UFH All LMWH Percentage 8.4 4.5 5.9 7.5 5.4 8.0 5.3 8.0 P = 0.016 P = 0.047

11. 0 5 10 15 FINESSE: Death at 90 Days Death (%) Montalescot G. TCT 2007. 1° UFH 1° LMWH Abx Fac UFH Abx Fac LMWH Ret/Abx Fac UFH Ret/Abx Fac LMWH All UFH All LMWH 5.4 2.4 4.7 5.6 4.3 5.9 3.8 5.6 P = 0.061 P = 0.065

12. FINESSE: Adjusted Odds Ratios for Efficacy and Safety Endpoints LMWH vs. UFH EndpointOR95% CIP TIMI major bleeding0.560.31 – 0.990.04 TIMI major bleeding0.560.31 – 0.990.04 Death/complications of MI to day 90 ( 1° )*0.73 0.52 – 1.030.07 Death/complications of MI to day 90 ( 1° )*0.73 0.52 – 1.030.07 Death to day 900.590.35 – 0.990.04 Death to day 900.590.35 – 0.990.04 Death or MI to day 300.580.35 – 0.960.03 Death or MI to day 300.580.35 – 0.960.03 Death, MI, urg revasc or refr. ischemia to day 300.470.31 – 0.720.0005 Death, MI, urg revasc or refr. ischemia to day 300.470.31 – 0.720.0005 Net benefit (death/MI/stroke/major bleeding)0.640.45 – 0.910.01 *Hazard ratio (logistic regression model)

13. ExTRACT–TIMI 25 Improved Efficacy in 2° PCI ExTRACT–TIMI 25 (N = 20,479) PCI by 30 days (n = 2,272) PCI by 30 days (n = 2,404) Enoxaparin (n = 10,256) UFH (n = 10,223) RRR = 23% P < 0.001 Enox 10.7% UFH 13.8% 0 3 6 9 12 15 051015202530 Death/MI (%) Days TIMI Major or Minor 4.6% vs. 4.0% P = 0.3 Antman EM, et al. N Engl J Med. 2006;354:1477-1488. Gibson CM, et al. J Am Coll Cardiol. 2007;49:2238-2246.

14. ACOS (STEMI) Registry 6,299 STEMI patients 2,021 Lysis 2,371 1° PCI 2,683 No early reperfusion * * * *P < 0.05, univariate analysis Death 10.0% UFH vs. 7.2% LMWH; P < 0.05 Zeymer U, et al. Thromb Haemost. 2008;99:150-154.

15. FAST–MI (STEMI) Registry Death Major bleeding Multivariate analysis: LMWH predicts survival 1,714 STEMI patients: 1,025 with reperfusion 55% 1 ° PCI 45% lysis Percent Danchin N. ACC 2007.

16. GRACE (ACS) Registry Death Major bleeding Collet JP, et al. Eur Heart J. 2005;26:2285-2293.

17. STEMI planned for 1° PCI ENOXAPARIN IV 0.5 mg/kg (± GP IIb/IIIa inhibitor) UFH IV 50 – 70 IU/kg if GP IIb/IIIa 70 – 100 IU/kg if no GP IIb/IIIa Dose adjusted to ACT Randomization (N = 850) 1° PCI and stenting 1° EP: Death, complication of MI, procedure failure or non-CABG major bleeding at 30 days Main 2° EP: Death, MI, refractory ischemia, urgent revasc. 6-month follow-up Patients who have already received UFH or LMWH or any other anticoagulant are excluded. All concomitant drugs accepted, except lytics; cross-over to other anticoagulant NOT accepted. ATOLL: Study Design

18. Conclusions Time has come for a change of anticoagulation in pPCI Favorable data with IV enoxaparin in expeditive care of ACS, elective PCI, pPCI Same dose regimen of enoxaparin whatever the antiplatelet regimen Optimal cost:benefit ratio