1. ACS Critical Pathways 2007 Teleconferences This activity is supported by an educational grant from the Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership. This activity is co-provided by the Network for Continuing Medical Education and EduPro Resources LLC. APRIL 11, 2007

2. Faculty Christopher P. Cannon, MD Associate Professor of Medicine Harvard Medical School Senior Investigator, TIMI Study Group Associate Physician, Cardiovascular Division Brigham and Women’s Hospital Boston, Massachusetts

3. The Network for Continuing Medical Education and EduPro Resources LLC require that CME/CNE faculty disclose, during the planning of an activity, the existence of any personal financial or other relationships they or their spouses/partners have with the commercial supporter of the activity or with the manufacturer of any commercial product or service discussed in the activity. Disclosure Statement

4. Christopher P. Cannon, MD , has served as a consultant to Abbott Laboratories, Alnylam Pharmaceuticals, Arena Pharmaceuticals, AstraZeneca Pharmaceuticals LP, Biosite, Bristol-Myers Squibb Company, Eisai Inc., GlaxoSmithKline, Johnson & Johnson, Merck & Co., Inc., Pfizer Inc, sanofi-aventis, Schering-Plough Corporation, Tethys Bioscience, and Vertex Pharmaceuticals. He has received honoraria from Accumetrics, AstraZeneca Pharmaceuticals LP, BGB New York, Bristol-Myers Squibb Company, DIME, Genentech, Inc., Merck & Co. Inc., Pfizer Inc, sanofi-aventis, and Schering-Plough Corporation, and has received research support from Accumetrics, AstraZeneca Pharmaceuticals LP, Merck & Co., Inc., and Schering-Plough Corporation. The team from Aurora St. Luke's Medical Center reports no such relationships. Faculty Disclosure Statement

5. Highlights From the American College of Cardiology 2007 Annual Scientific Session Christopher P. Cannon, MD

7. COURAGE C linical O utcomes U tilizing R evascularization and A ggressive G uideline-Driven Drug E valuation

12. COURAGE: Risk Factor Goals Boden WE, et al. N Engl J Med. 2007;356. Published online March 27, 2007. 30-45 min. moderate intensity 5x/week Physical Activity Initial BMI Weight Loss Goal 25-27.5 BMI <25 >27.5 10% relative weight loss Body Weight by BMI <130/85 mm Hg Blood Pressure HbA lc <7.0% Diabetes <200 mg/day Dietary Cholesterol 60-85 mg/dL LDL-C (primary goal) >40 mg/dL HDL-C (secondary goal) <150 mg/dL Triglyceride (secondary goal) <30% calories / <7% calories Total Dietary Fat / Saturated Fat Cessation Smoking Goal Variable

15. COURAGE: Baseline Characteristics – Angina Boden WE, et al. N Engl J Med. 2007;356. Published online March 27, 2007. .24 .53 .83 148 (13) 341 (30) 425 (37) 221 (19) 2 (<1) 5 1-15 3 1-6 135 (12) 340 (30) 409 (36) 261 (23) 3 (<1) 5 1-15 3 1-6 Angina CCS class (no, %) 0 I II III Missing data Duration of angina (months) Median Interquartile range Episodes/week with exertion or at rest within last month Median Interquartile range P value OMT (N = 1138) PCI + OMT (N = 1149) Characteristic

16. COURAGE: Survival Free of Death From Any Cause and MI No. at Risk OMT 1138 1017 959 834 638 408 192 30 PCI+OMT 1149 1013 952 833 637 417 200 35 Years 0 1 2 3 4 5 6 0.0 0.5 0.6 0.7 0.8 0.9 1.0 PCI + OMT: 19%* OMT: 18.5%* Hazard ratio: 1.05 95% CI (0.87-1.27) P = .62 7 Boden WE, et al. N Engl J Med. 2007;356. Published online March 27, 2007. Survival Free of Death From Any Cause and MI *Cumulative event rates at a median of 4.6 years.

17. COURAGE: Cumulative Event Rates at a Median of 4.6 Years <.001 0.51–0.71 0.60 32.6 21.1 Revasc. (PCI or CABG) .56 0.84–1.37 1.07 11.8 12.4 Hospitalization for ACS .19 0.80–3.04 1.56 1.8 2.1 Stroke .33 0.89–1.43 1.13 12.3 13.2 Nonfatal MI .38 0.65–1.16 0.87 8.3 7.6 Death .62 0.87–1.27 1.05 19.5 20 Death, MI, stroke .62 0.87–1.27 1.05 18.5 19 Death, MI P value 95% CI Hazard ratio OMT (%) PCI + OMT (%) Outcome Boden WE, et al. N Engl J Med. 2007;356. Published online March 27, 2007.

18. COURAGE: Overall Survival No. at Risk OMT 1138 1073 1029 917 717 468 302 38 PCI+OMT 1149 1094 1051 929 733 488 312 44 Years 0 1 2 3 4 5 6 0.0 0.5 0.6 0.7 0.8 0.9 1.0 PCI + OMT: 7.6%* OMT: 8.3%* 7 Hazard ratio: 0.87 95% CI (0.65-1.16) P = .38 Boden WE, et al. N Engl J Med. 2007;356. Published online March 27, 2007. Overall Survival *Cumulative event rates at a median of 4.6 years.

21. MERLIN TIMI-36 M etabolic E fficiency with R anolazine for L ess I schemia in N on-ST Elevation Acute Coronary Syndromes

23. MERLIN TIMI-36: Study Design Follow-up visits: Day 14, Month 4, Q4 Months Placebo (n = 3,281) Matched IV/PO Ranolazine (n = 3,279) IV -> PO Standard Therapy for ACS Morrow DA, et al. Am Heart J. 2006;151:1186. UA/NSTEMI (N = 6560) 1) Rest symptoms within 48 h 2) High-risk features Holter monitoring at enrollment x 7d Final Visit Additional end points : Exercise performance, new/worsening heart failure, quality of life, extent of myocardial injury, clinically significant arrhythmia . Duration Event-driven Mean Follow-up: Median, 348 Days Primary end point: Composite of CV death, MI, or recurrent ischemia Secondary end point: Composites of CV death, MI, severe recurrent ischemia; and positive Holter at 30 days

24. MERLIN: Efficacy Results Morrow D, et al. Presented at: American College of Cardiology 2007 Scientific Sessions; March 27, 2007; New Orleans, Louisiana. .030 0.87 13.9 16.1 Recurrent ischemia .87 0.99 10.4 10.5 CV death/MI .11 0.92 21.8 23.5 CV death/recurrent ischemia (primary end point) P value Hazard Ratio Ranolazine (n = 3279) Placebo (n = 3281) End point

25. MERLIN: Safety Results Morrow D, et al. Presented at: American College of Cardiology 2007 Scientific Sessions; March 27, 2007; New Orleans, Louisiana. <.001 0.89 73.1% 83.1% Clinically significant arrhythmia on Holter (% of patients) .84 0.97 99 102 Symptomatic documented arrhythmia (number of patients) .43 0.87 56 65 Sudden cardiac death (number of patients) .91 0.99 172 175 Death, any cause (number of patients) P value Hazard ratio Ranolazine (n = 3268) Placebo (n = 3273) End point

27. Danish Registry

32. Danish Registry: Results Maeng M, et al. Presented at: American College of Cardiology 2007 Scientific Sessions; March 24, 2007; New Orleans, Louisiana. <.0001 4.0 Data not Presented Data not Presented MI, 12-15 months .31 1.14 3.2 3.0 Overall MI .29 0.90 4.4 6.2 Overall death .029 10.9 0.09 0.009 Definite stent thrombosis, 12-15 months NS 0.92 1.8 2.15 Overall probable, possible, or definite stent thrombosis (ARC definition) <.0001 0.57 4.6 7.1 Target lesion revascularization P value Adj. RR DES (%) (n = 3268) BMS (%) (n = 8847) End point

34. REACH Update: An International Risk Prediction Model for Recurrent CV Events Re duction of A therothrombosis for C ontinued H ealth (International Risk Reduction Model for Recurrent CV Events)

37. REACH: Multivariable-adjusted HR and P Value for Variables Considered Morrow D, et al. Presented at: American College of Cardiology 2007 Scientific Sessions; March 27, 2007; New Orleans, Louisiana. Number at risk: 27,632; Number of events: 1,126. .2187 1.18 Hypertension therapy (yes/no) .0352 .87 Acetyl salicylic acid (yes/no) <.0001 .72 Statins (yes/no) <.0001 1.78 Cardiac failure (yes/no) <.0001 1.47 CV event in past year (yes/no) .0013 1.00, 1.20, 1.44 1, 2 or 3 vasc. beds (CAD, CVD, PAD) <.0001 1.60 Diabetes (yes/no) <.0001 1.42 Smoking (current vs other) <.0001 1.03 Age (year) .7087 1.02 Gender (male) P value HR per unit Variable (unit)

39. ACUITY: One Year Results A cute C atheterization and U rgent I ntervention T riage Strateg Y

40. ACUITY: Patient Follow-up at 1 Year* All patients N = 13,819 25 Withdrawn 62 Lost to Follow-up Heparin + IIb/IIIa 4,516 (98.1%) 1-year FU Bivalirudin + IIb/IIIa 4,502 (97.8%) 1-year FU Bivalirudin alone 4,521 (98.0%) 1-year FU 33 Withdrawn 69 Lost to Follow-up 25 Withdrawn 66 Lost to Follow-up *End points adjudicated: Composite ischemia (death, MI, unplanned revasc) and stent thrombosis Stone GW. Presented at: American College of Cardiology 2007 Scientific Sessions; March 26, 2007; New Orleans, Louisiana. Heparin + GP IIb/IIIa 4,603 Bivalirudin + GP IIb/IIIa 4,604 Bivalirudin alone 4,612 R

41. ACUITY: Ischemic Composite End Point (Death, MI, unplanned revascularization for ischemia) 0 30 60 90 120 150 180 210 240 270 300 330 360 390 0 5 15 25 Ischemic Composite (%) Days From Randomization 10 20 UFH/Enoxaparin + IIb/IIIa Bivalirudin + IIb/IIIa Bivalirudin alone Bivalirudin alone vs Hep + GPI HR [95% CI] = 1.05 (0.95-1.17) Bivalirudin + GPI vs Hep + GPI HR [95% CI] = 1.05 (0.94-1.16) UFH/Enoxaparin + GPI vs Bivalirudin + GPI vs Bivalirudin Alone Stone GW. Presented at: American College of Cardiology 2007 Scientific Sessions; March 26, 2007; New Orleans, Louisiana. Estimate P (log rank) 30-day 7.4% .36 7.8% .34 7.9% — Estimate P (log rank) 16.3% .38 16.5% .31 16.4% 1-year — P = .55

42. ACUITY: Stent Thrombosis (Protocol Defn.) 0 30 60 90 120 150 180 210 240 270 300 330 360 390 0 3 4 5 Stent Thrombosis (%) Days From Randomization 2 1 Drug-eluting Stents (DES) vs Bare-Metal Stents (BMS) Estimate P (log rank) ≥ 1 DES (N = 4630) .38 2.2% 1-year Stone GW. Presented at: American College of Cardiology 2007 Scientific Sessions; March 26, 2007; New Orleans, Louisiana. All BMS (N = 2528) 2.3% All (N = 7158) 2.2%

43. Mortality (%) Days From Randomization 0 30 60 90 120 150 180 210 240 270 300 330 360 390 0 5 15 30 10 25 20 1-year Estimate ACUITY: Impact of MI and Major Bleeding (non-CABG) in the First 30 Days on Risk of Death Over 1 Year 28.9% 12.5% 8.6% 3.4% Stone GW. Presented at: American College of Cardiology 2007 Scientific Sessions; March 26, 2007; New Orleans, Louisiana. Major Bleed only (without MI) (N = 551) 12.5% 28.9% Both MI and Major Bleed (N = 94) 3.4% No MI or Major Bleed (N = 2,557) MI only (without Major Bleed) (N = 611) 8.6%

45. Featured Institution Aurora St. Luke’s Medical Center Milwaukee, Wisconsin

47. Progress Checklist: Immediate Goals Circulate discharge plan and other tools to all cardiology, ED, and CV nursing staff for comments  Circulate pathways to all cardiology, ED, and CV nursing staff for comments  Develop draft pathways  Assemble team and set up meeting of working group 

48. Progress Checklist: Short-term Goals/Activities Grand rounds/conference: Cardiology/IM  Grand rounds/conference: Emergency Dept.  Grand rounds/conference: Nursing  Circulate memo  Launch critical pathways  Finalize critical pathways 

49. Progress Checklist: Long-term Goals/Activities  NRMI  AHA Get With The Guidelines  ACC National Cardiovascular Data Registry  CRUSADE  GRACE  REACH  Other Monitor data: which registry? 

50. Question-and-Answer Session

51. Concluding Remarks Christopher P. Cannon, MD Next Program Christopher P. Cannon, MD Wednesday, May 16, 2007 12:00 Noon Eastern Time (9:00 AM Pacific Time) The AHA/ACC/SCAI/ACS/ADA Science Advisory on Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents