Ongoing Trials in Managing Myocardial Ischemia

MERLIN-TIMI 36: Study design

IV/oral ranolazine Placebo

Patients with non-ST elevation ACStreated with standard medical/interventional therapies

N ~ 5500

Anticipated completion 2006

Primary outcome:CV death, MI, recurrent ischemia

RandomizedDouble-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

COURAGE: Study design

Boden WE et al. Am Heart J. 2006.

Aggressive medical therapy Aggressive 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

COURAGE: Lifestyle modification goals

Smoking Cessation

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/m2) <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 characteristics Goal

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.

BARI 2D: Study design

Aggressive pharmacologic CV therapy

Aggressive pharmacologic CV therapy +

coronary revascularization

Patients with type 2 diabetes and angina or asymptomatic myocardial ischemiaN = 2322

Primary outcome: All-cause deathSecondary 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

Randomize

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.

Control (medium)Control (medium)

Kawamoto A et al. Circulation. 2001;103:634-7.

EPCEPC

106 human cells administered 3 hours after induction of myocardial ischemia in male athymic nude rats

EPC = endothelial progenitor cells

Transplanted EPCs: Reduction in fibrosis

Stem cell therapy for intractable angina:Study design

Saline control 1 x 105/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 studiesGCSF = granulocyte colony-stimulating factor

5 x 104/kg* 5 x 105/kg

Injected into hibernating/ischemic myocardium

Double-blind, placebo-controlled

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