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.

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 None 1.0 Mild 2.1 Moderate 2.5 Severe 10.9 Moderate 3.7 Rao SV, et al. Am J Cardiol. 2005;96:

Can we improve safety in PCI with enoxaparin?

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

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:

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 = Dumaine R, et al. Arch Intern Med. 2007;167:

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.

FINESSE: TIMI Major Bleeding ° 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 P = P = P = P = NS

Can we improve safety and efficacy in primary PCI?

FINESSE: Death, ReMI, Urgent Revasc, or Refractory Ischemia Through Day 30 Montalescot G. TCT ° UFH 1° LMWH Abx Fac UFH Abx Fac LMWH Ret/Abx Fac UFH Ret/Abx Fac LMWH All UFH All LMWH Percentage P = P = 0.047

FINESSE: Death at 90 Days Death (%) Montalescot G. TCT ° UFH 1° LMWH Abx Fac UFH Abx Fac LMWH Ret/Abx Fac UFH Ret/Abx Fac LMWH All UFH All LMWH P = P = 0.065

FINESSE: Adjusted Odds Ratios for Efficacy and Safety Endpoints LMWH vs. UFH EndpointOR95% CIP TIMI major bleeding – TIMI major bleeding – Death/complications of MI to day 90 ( 1° )* – Death/complications of MI to day 90 ( 1° )* – Death to day – Death to day – Death or MI to day – Death or MI to day – Death, MI, urg revasc or refr. ischemia to day – Death, MI, urg revasc or refr. ischemia to day – Net benefit (death/MI/stroke/major bleeding) – *Hazard ratio (logistic regression model)

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 < Enox 10.7% UFH 13.8% 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: Gibson CM, et al. J Am Coll Cardiol. 2007;49:

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:

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.

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

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

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