1 ExTRACT-TIMI 25 : New Data Elliott M. Antman, MD This presentation reflects the views of the presenter and does not necessarily reflect the views of the American College of Cardiology Content Distributed by Cardiosource

2 Disclosure Accumetrics, Inc. Amgen, Inc. AstraZeneca Pharmaceuticals LP Baxter Bayer Healthcare LLC Beckman Coulter, Inc. Biosite Incorporated Bristol-Myers Squibb CardioKinetix CV Therapeutics, Inc. Eli Lilly and Company FoldRxGlaxoSmithKline INO Therapeutics LLC Inotek Pharmaceuticals Corporation The National Institutes of Health Integrated Therapeutics Corporation KAI Pharmaceuticals Merck & Co., Inc. Millennium Pharmaceuticals, Inc. Novartis Pharmaceuticals Nuvelo, Inc. Ortho-Clinical Diagnostics, Inc. Pfizer, Inc. Roche Diagnostics Corporation Roche Diagnostics GmbH Sanofi-Aventis Sanofi-Synthelabo Recherche Schering-Plough Research Institute St Jude Medical The TIMI Study Group has received research / grant support in the past 2 yrs through the Brigham & Women’s Hospital with funding from (in alphabetical order):

3 STEMI < 6 h Lytic eligible Lytic choice by MD (TNK, tPA, rPA, SK) ENOX < 75 y: 30 mg IV bolus SC 1.0 mg / kg q 12 h (Hosp DC) ≥ 75 y: No bolus SC 0.75 mg / kg q 12 h (Hosp DC ) CrCl < 30: 1.0 mg / kg q 24 h Double-blind, double-dummy ASA Day 30 1° Efficacy Endpoint: Death or Nonfatal MI 1° Safety Endpoint: TIMI Major Hemorrhage Protocol Design UFH 60 U / kg bolus (4000 U) Inf 12 U / kg / h (1000 U / h) Duration: at least 48 h Cont’d at MD discretion N Engl J Med 2006;354:

4 Main Results Primary Endpoint: Death or non-fatal re-MI by 30 days Primary Endpoint: Death or non-fatal re-MI by 30 days Main Secondary Endpoint: Death, non-fatal re-MI, urgent revascularization by 30 days Main Secondary Endpoint: Death, non-fatal re-MI, urgent revascularization by 30 days UFH ENOX Days % % RR = 0.83 p = RR = 0.81 p = N Engl J Med 2006;354: % RRR in reMI by 48 h (P=0.002) 19% RRR in Death/MI by 72 h (P<0.001) 33% RRR in reMI by 48 h (P=0.002) 19% RRR in Death/MI by 72 h (P<0.001) 12% RRR in by 48 h (P=0.02)

5 Death or Nonfatal MI Treatment Effect Over Time UFH (%) ENOX (%) RRR (%) ARD (%) 0.5 NNT Days From Rand. RR ENOX Better UFH Better P<0.001

6 Bleeding Endpoints (TIMI) 30 Days Bleeding Endpoints (TIMI) 30 Days UFH ENOX % Events Major Bleed (Total) ICH ARD 0.7% RR 1.53 P< ARD 0.1% RR 1.27 P = 0.14 Nonfatal Major Bleed ARD 0.4% RR 1.39 P = ARD 0.4% RR 1.84 P = Fatal Major Bleed N Engl J Med 2006;354:

7 Net Clinical Benefit at 30 Days Death or Nonfatal MI or Nonfatal ICH Death or Nonfatal MI or Nonfatal Major Bleed Death or Nonfatal MI or Nonfatal Disabl. Stroke ENOX Better UFH Better RR UFH (%)ENOX (%)RRR (%) Prespecified Definitions P < N Engl J Med 2006;354:

8 For Every 1000 Pts Treated with Enoxaparin Events / 1000 Pts Nonfatal reMI Urgent Revasc. Death Nonfatal TIMI Major Bleed (No increase in nonfatal ICH) + N Engl J Med 2006;354:

9 For Every 1000 Pts Treated with Enoxaparin Age 75 Nonfatal reMI Nonfatal Urgent Revasc. Death Nonfatal TIMI Major Bleed Events / 1000 Pts AHA 2006

10 For Every 1000 Pts Treated with Enoxaparin Gender Events / 1000 Pts DeathNFMIUR Nonfatal TIMI Major Bleed (No increase in nonfatal ICH)

11 For Every 1000 Pts Treated with Enoxaparin Diabetes Events / 1000 Pts Death p = p = 0.39 NFMI p = p < UR p = 0.76 p = Nonfatal TIMI Major Bleed p = 0.21 p = 0.04 (No increase in nonfatal ICH) DM No DM AHA 2006

12 For Every 1000 Pts Treated with Enoxaparin Clopidogrel Use (No PCI) No Clopidogrel Clopidogrel Used Events / 1000 Pts Death, MI, Rec Isch, Stroke Nonfatal Major Bleed AHA 2006

13 Death or Nonfatal MI - Day 30 Lytic Administered ENOX Better UFH Better RR UFH (%)ENOX (%)RRR (%) SK (N=4139) TNK (N=3986) rPA (N=1122) tPA (N=11,175) Interaction Tests P = NS Interaction Tests P = NS AHA 2006

14 Clinical Implication A strategy of ENOX is clearly preferable to the current standard of UFH as the antithrombin to support fibrinolysis, the most common form of reperfusion for STEMI used worldwide. A strategy of ENOX is clearly preferable to the current standard of UFH as the antithrombin to support fibrinolysis, the most common form of reperfusion for STEMI used worldwide.