1. Ongoing Trials in Managing Myocardial Ischemia

2. MERLIN-TIMI 36: Study design IV/oral ranolazinePlacebo Patients with non-ST elevation ACS treated with standard medical/interventional therapies N ~ 5500 Anticipated completion 2006 Primary outcome: CV death, MI, recurrent ischemia Randomized Double-blind Lüscher T. Eur Heart J Suppl. 2004;6(suppl I):I17-8. MERLIN-TIMI 36 Study Group. www.clinicaltrials.gov. Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST elevation acute coronary syndrome–Thrombolysis In Myocardial Infarction 36

3. COURAGE: Study design Boden WE et al. Am Heart J. 2006. Aggressive medical therapyAggressive medical therapy + PCI CCS Class I–III angina, stable post-MI, or documented asymptomatic myocardial ischemia N = 2287 5 years Primary outcome: All-cause mortality, nonfatal MI Randomized Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation

4. COURAGE: Lifestyle modification goals SmokingCessation Total dietary fat<30% of calories Saturated fat<7% of calories Dietary cholesterol<200 mg/day Physical activity≥30 min moderately intensive exercise 5 times per week BMI (kg/m 2 )<25 (if baseline 25.0–27.5) 10% relative weight loss (if baseline BMI >27.5) Boden WE et al. Am Heart J. 2006. Lifestyle characteristicsGoal

5. COURAGE: Medical therapy goals LDL-C (mg/dL)60–85 HDL-C (mg/dL)≥40 Triglycerides (mg/dL)<150 BP (mm Hg)<130/85 <130/80 if diabetes or renal disease present A1C (%)<7.0 Boden WE et al. Am Heart J. 2006.

6. BARI 2D: Study design Aggressive pharmacologic CV therapy Aggressive pharmacologic CV therapy + coronary revascularization Patients with type 2 diabetes and angina or asymptomatic myocardial ischemia N = 2322 Primary outcome: All-cause death Secondary outcome: All-cause death, Q-wave MI, stroke Double-blind, 2x2 factorial Bypass Angioplasty Revascularization Investigation 2 Diabetes Insulin–sensitizer-based antidiabetic therapy Insulin-based antidiabetic therapy Sobel BE et al. Circulation. 2003;107:636-42. 5 years Randomize

7. Vascular endothelial growth factor Fibroblast growth factor Cell therapy Biological revascularization: New frontiers Kawamoto A et al. Circulation. 2001;103:634-7. Losordo DW and Kawamoto A. Circulation. 2002;106:3002-5.

8. Control (medium) Kawamoto A et al. Circulation. 2001;103:634-7.EPC 10 6 human cells administered 3 hours after induction of myocardial ischemia in male athymic nude rats EPC = endothelial progenitor cells Transplanted EPCs: Reduction in fibrosis

9. Stem cell therapy for intractable angina: Study design Saline control1 x 10 5 /kg Patients with intractable CCS class III or IV angina not suitable for CABG or PCI N = 24 Cross-over permitted at 6 months (CCS class III or IV, abnormal SPECT, ETT < 6 min) Losordo DW et al. VBWG US chapter meeting. March 2006; Atlanta, Ga. 5 days GCSF (plus ASA, clopidogrel, statin)/apheresis/CD34 + cell selection *Sub-therapeutic dose in preclinical studies GCSF = granulocyte colony-stimulating factor 5 x 10 4 /kg*5 x 10 5 /kg Injected into hibernating/ischemic myocardium Double-blind, placebo-controlled

10. Summary Despite availability of effective medical and interventional modalities, patients with stable CAD continue to experience ischemic events In special populations (eg, women) CAD needs to be more aggressively diagnosed and treated Ongoing trials may help better define the role of aggressive medical therapy with/without PCI