Ongoing Trials in Managing Myocardial Ischemia

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Ongoing Trials in Managing Myocardial Ischemia
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MERLIN-TIMI 36 Study design
Metabolic Efficiency with Ranolazine for Less
Ischemia in Non-ST elevation acute coronary
syndromeThrombolysis In Myocardial Infarction 36
Patients with non-ST elevation ACStreated with
standard medical/interventional therapiesN 5500
IV/oral ranolazine
Placebo
RandomizedDouble-blind
Anticipated completion 2006
Primary outcomeCV death, MI, recurrent ischemia
Lüscher T. Eur Heart J Suppl. 20046(suppl
I)I17-8. MERLIN-TIMI 36 Study Group.
www.clinicaltrials.gov.
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COURAGE Study design
Clinical Outcomes Utilizing Revascularization and
Aggressive druG Evaluation
Boden WE et al. Am Heart J. 2006.
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COURAGE Lifestyle modification goals
Lifestyle characteristics
Goal
Smoking Cessation
Total dietary fat lt30 of calories
Saturated fat lt7 of calories
Dietary cholesterol lt200 mg/day
Physical activity 30 min moderately intensive exercise 5 times per week
BMI (kg/m2) lt25 (if baseline 25.027.5) 10 relative weight loss (if baseline BMI gt27.5)
Boden WE et al. Am Heart J. 2006.

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COURAGE Medical therapy goals
LDL-C (mg/dL) 6085
HDL-C (mg/dL) 40
Triglycerides (mg/dL) lt150
BP (mm Hg) lt130/85lt130/80 if diabetes or renal disease present
A1C () lt7.0
Boden WE et al. Am Heart J. 2006.
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BARI 2D Study design
Bypass Angioplasty Revascularization
Investigation 2 Diabetes
Patients with type 2 diabetes and angina or
asymptomatic myocardial ischemiaN 2322
Aggressive pharmacologic CV therapy
Aggressive pharmacologic CV therapy coronary
revascularization
Randomize
Randomize
Insulinsensitizer-based antidiabetic therapy
Insulin-based antidiabetic therapy
5 years
Primary outcome All-cause deathSecondary
outcome All-cause death, Q-wave MI, stroke
Double-blind, 2x2 factorial
Sobel BE et al. Circulation. 2003107636-42.
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Biological revascularization New frontiers

• Vascular endothelial growth factor
• Fibroblast growth factor
• Cell therapy

Kawamoto A et al. Circulation. 2001103634-7.Los
ordo DW and Kawamoto A. Circulation.
20021063002-5.


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Transplanted EPCs Reduction in fibrosis
106 human cells administered 3 hours after
induction of myocardial ischemia in male athymic
nude rats
Kawamoto A et al. Circulation. 2001103634-7.
EPC endothelial progenitor cells
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Stem cell therapy for intractable anginaStudy
design

Patients with intractable CCS class III or IV
angina not suitable for CABG or PCI N 24
5 days GCSF (plus ASA, clopidogrel,
statin)/apheresis/CD34 cell selection
Double-blind, placebo-controlled
Saline control
1 x 105/kg
5 x 104/kg
5 x 105/kg
Injected into hibernating/ischemic myocardium
Cross-over permitted at 6 months(CCS class III
or IV, abnormal SPECT, ETT lt 6 min)
Losordo DW et al. VBWG US chapter meeting. March
2006 Atlanta, Ga.
Sub-therapeutic dose in preclinical studies GCSF
granulocyte colony-stimulating factor
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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