Targeting Inflammation Using Salsalate in CardioVascular Disease

Inclusion Criteria

Eligibility will be based upon the presence of established coronary artery disease including

• previous myocardial infarction (≥6 months ago), or
• previous coronary bypass surgery (> 12 months ago), or
• stable angina, or
• significant non-calcified plaque in at least one coronary artery, or
• abnormal exercise tolerance test or
• an area of reversible ischemia on nuclear imaging study or pharmacologic stress, with subsequent revascularization, or angioplasty, or
• abnormal exercise treadmill stress test with or without nuclear imaging or echocardiography with the following exclusions:

Exclusions based on nuclear imaging:

• Transient cavity dilation
• More than one vascular territory involved with reversible defect (multiple defects)
• Reversible defects involving the anterior wall, septum or apex (LAD territory)

Exclusions based on echocardiography imaging:

• More than one vascular territory involved with inducible wall motion abnormalities (multiple defects)
• Inducible wall motion abnormalities involving the anterior wall, septum or apex (LAD territory)

Subjects should be at list 6 months after a myocardial infarction and/or revascularization procedure to be eligible.

In addition, subjects must be:

• aged 21- 75 years inclusive,
• BMI ≥ 27 kg/m2 and ≤ 35 kg/m2 if female and ≤ 40 kg/m2 if male (a BMI ≥24.5 for subjects from Asian origin)
• on a stable dose of an HMG CoA reductase inhibitor (statin) for 1 month at screening or unable to tolerate a statin,
• have normal renal function, (note estimated creatinine clearance calculated using Cockcroft-Gault (CG) equation ≥60 at screening [eCrCLCG (ml/min) = [(140 - age) x weight (kg)]/[SCr(mg/dl) x 72] x [0.85 if female],
• have liver function (ALT, AST) 65 bpm
• Systolic blood pressure > 160 mm Hg
• Diastolic BP > 100 mm Hg
• Persons with allergies to contrast material
• History of asthma if unable to tolerate beta blocker
• Allergy to iodinated contrast material or shellfish
• Allergy to nitroglycerin
• BMI > 35 kg/m2 if female and > 40 kg/m2 if male
• Body weight > 350 lbs
• Use of drugs for weight loss [e.g. Xenical (orlistat), Meridia (sibutramine), Acutrim (phenylpropanolamine) or similar over-the counter medications] within three months of screening
• Surgery within 30 days of screening
• History of acquired immune deficiency syndrome or human immunodeficiency virus (HIV)
• Poor mental function or history of dementia/ Alzheimer's Disease or on medications used for treatment of dementia [e.g. Tacrine (Cognex), Rivastigmine (Exelon), Galantamine (Razadyne, Reminyl), Donepezil (Aricept), Memantine (Namenda)] or any other reason to expect patient difficulty in complying with the requirements of the study
• Medicine for erectile dysfunction within 72 hours prior to MDCTA
• History of significant chronic rheumatologic or other chronic inflammatory disease (including foot ulcers)
• Prior hemorrhagic stroke
• persons with known aspirin allergy
• Use of continuous oral corticosteroid treatment (more than 2 weeks), or patients requiring corticosteroids within 3 months
• Anti-diabetic medication including thiazolidinedione (pioglitazone or rosiglitazone), or insulin or Extendin-4 (Byetta)
• History of peptic ulcer or gastritis within 5 years
• Positive stool guaiac
• Hemoglobin 2 standard deviations below normal
• Low platelet count (2 standard deviations below normal)
• Known bleeding disorder
• Coumadin (warfarin compounds)
• History of type 1 diabetes and/or history of ketoacidosis
• Daily use of NSAIDS (including salsalate) for arthritis
• History of malignancy, except subjects who have been disease-free for greater than 5 years, or whose only malignancy has been basal or squamous cell skin carcinoma
• History of drug or alcohol abuse, or current weekly alcohol consumption >14 units/week (1 unit = 1 beer, 1 glass of wine, 1 mixed cocktail containing 1 ounce of alcohol)
• Use of probeneci