The purpose of this investigation is to compare subjects at high risk for silent myocardial ischemia in the placebo group to subjects at high risk for silent myocardial ischemia in the ranolazine group to determine if ranolazine can be used as a treatment to decrease silent myocardial ischemia (SMI). Subjects at high risk for silent myocardial ischemia are defined in this protocol as diabetics with stable ischemic heart disease. This study will look at the impact ranolazine treatment has on biomarkers that have been shown to be highly associated with increased risk of morbidity and mortality in relation to SMI. If the hypothesis is correct, further studies can be conducted to determine if treatment with ranolazine has impact on long-term outcomes such as hospitalizations, myocardial infarction, congestive heart failure or sudden cardiac death.

Inclusion Criteria:

• Subjects at risk for silent myocardial ischemia as defined by:

• Stable ischemic heart disease as defined by:

  • Obstruction of at least one epicardial vessel of > 50 percent by invasive or non-invasive coronary angiography, or
  • Evidence of ischemia or infarct on SPECT imaging, or
  • History of myocardial infarction > 3 months ago, or
  • Stent placement (PCI) > 3 months ago, or
  • Coronary artery bypass grafting (CABG) > 3 months ago AND

• Type 2 diabetics as defined by:

  • HgbA1C ≥ 6.5 percent, or

  • Fasting Blood Glucose > 125 mg/dL on two or more blood draws, or

  • Random Blood Glucose of ≥ 200 mg/dL on a single blood draw, or

  • Previous diagnosis of type 2 diabetes listed in the subject's medical record AND

    - On Optimal Medical Therapy as defined as being on ALL of the following at time of enrollment:

  • Beta Blocker

  • Aspirin

  • Statin AND

• Females < 60 who have not been free of menstruation for 2 years (menopause diagnosed) or who do not have documented history of hysterectomy must be willing to use at least one form of birth control (including abstinence as an option) for the duration of the study. If condoms are the method chosen, they are strongly urged to use a second form of birth control in addition to condoms.

AND

Screening Criteria met:

• hs cTnT > 0.014 ng/mL

Exclusion Criteria:

• Percutaneous intervention/stent placement in the past 3 months
• Coronary artery bypass grafting in the past 3 months
• Treatment with ranolazine in the past 12 months
• Significant lung disease, COPD or use of supplemental oxygen
• Cirrhosis
• Estimated Glomerular Filtration Rate (GFR) < 30
• Subject taking strong CYP3A inhibitors (ketoconazole, itraconazole, clarithryomycin, nefazodone, nelfinavir, ritonavir, indinavir and saquinavir)
• Subject taking strong CYP3A inducers (rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, St. John's wort)
• Subjects taking P-gp Inhibitors (cyclosporine)
• Subject is taking concurrent simvastatin in > 20 mg/day
• Subject is taking metformin > 1700 mg/day
• NYHA Class 3 or 4 Heart Failure (severe)
• Canadian Cardiovascular Society Grade 4 Angina
• Unstable angina defined as a new angina occurring after minimal exercise or at rest OR a significant increase in angina severity (≥ 2 CCS grades) occurring with minimal exertion, with high clinical suspicion of acute coronary syndrome.
• Planned PCI or Cardiac Surgery
• Pregnant females or females trying to become pregnant
• Breast-feeding females
• Subjects younger than age 30 or older than age 85
• Lactose Intolerance (placebo has lactose monohydrate)
• Lactose/Milk allergy (placebo has lactose monohydrate)
• QTc > 500 msec