Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis Trial

Inclusion criteria

• Male or female patients >45 or >40 years with known atherosclerotic events (examples include MI, Stroke) and able to provide informed consent (females must be either post-menopausal for one year, surgically sterile, or using effective contraception. Oral contraceptives are disallowed.
• Patients with Type II Diabetes with HbA1c ≤ 9.0 on stable anti-glycemic regimen that may include oral and/or injectable therapy (GLP-1/Insulin etc.). Changes in dose of glycemic regimen is allowed during the course of the trial if felt to be clinically appropriate.
• GFR <90 and evidence of proteinuria (Urine albumin/creatinine ratio of >30 mg/g or equivalent) in a urine specimen within 12 months OR GFR <60 mg/g regardless of proteinuria.
• Patients must be on ACE and/or ARB therapy with no planned dose adjustments.

Exclusion criteria

• Uncontrolled hypertension (SBP>160 and/or DBP>95 mmHg at visit 0 (screening) and SBP >145 mm Hg at visit 2).
• GFR (MDRD) of <15 at Visit 0 (screening).
• Hyperkalemia defined as serum K+≥ 5.1 meq/L at visit 0 (screening).
• LDL cholesterol >150 mg/dl.
• Plasma triglycerides >400 mg/dl.
• Contraindications to MRI (metallic implants, severe claustrophobia).
• Acute coronary syndrome, Transient ischemic attack, CVA or critical limb ischemia during the last 6 months or coronary/peripheral revascularization within the last 3 months.
• Evidence of a secondary form of hypertension.
• Initiation of new therapy with statins, ACEI/ARB, anti-oxidants, CCBs, diuretics, β blockers.
• Type I diabetes mellitus
• Known contraindication, including history of allergy to Spironolactone.
• . Any surgical or medical condition which might alter pharmacokinetics of drug (e.g. renal transplant, liver failure, liver transplant).
• Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia.
• Significant hyponatremia defined as Na <130 meq/L.
• History of prior malignancy including leukemia and lymphoma (but not basal cell skin cancer, cured squamous cell cancer and localized Prostate cancer).
• History of any severe, life-threatening disease.
• Any surgical or medical conditions which places the patient at higher risk derived from his/her participation into the study, or likely to prevent patient from complying with requirements.
• History of drug abuse within the last 2 years, noncompliance and unwillingness/inability to consent.
• Pregnant women and nursing mothers.
• Class III or IV Congestive Heart Failure.
• Primary Hyperaldosteronism.