Study to Evaluate the Effect of Simvastatin, Losartan and Pioglitazone on Patients With Peripheral Arterial Disease.

• Men and women =90 years of age.
• Bilateral lower extremity PAD requiring revascularization. Both extremities must have at least 1denovo atherosclerotic lesion
• Able to space bilateral atherectomy procedures by at least 6 weeks.
• Willing to provide informed consent to participation in genetic studies.
• Simvastatin Substudy
• LDL-C >100 mg/dL and \<250 mg/dL TG\<350 mg/dL
• Not currently receiving or having taken a statin (simvastatin, lovastatin, rosuvastatin, atorvastatin, or pravastatin) or a combination product containing a statin for the previous 3 months.
• Losartan Substudy
• Diagnosis of hypertension with systolic blood pressure >120 mm Hg but \<160 mm Hg, and diastolic blood pressure >80 mm Hg but \<100 mm Hg.
• Not currently receiving or having taken an ACEi or ARB.
• Pioglitazone Substudy
• Type II diabetes mellitus
• HbA1c >5.5% and \< 8.5%
• Otherwise on a stable glucose lowering regimen where no changes are expected in oral regimen, or where no changes in insulin doses of more than 10 U are expected.
• Not currently receiving or having taken a thiazolidinedione (rosiglitazone or pioglitazone) or a combination product containing a thiazolidinedione or the previous 12 months.

Exclusion Criteria:

• Patient is pregnant, breast-feeding, or expecting to conceive during the study including the 14-day post study follow-up.
• current condition, therapy, lab abnormality, mental legal incapacitation that in the investigator's judgment might confound the results of the study.
• Patient is currently participating in or has participated in a study with an investigational compound within 30 days of Visit 1.
• Patient has donated and/or received blood (including phlebotomy of >300 mL) within 2 months prior to study.
• Surgery or significant trauma within 2 months prior to Visit 1.
• Patient is a user of recreational or illicit drugs or has had a recent history \<1yr drug/alcohol abuse>2 alcoholic drinks per day).
• Patient was \<80% compliant with dosing during the placebo run-in period AND, in the opinion of the investigator, believed to be unable to maintain at least an 80% compliance with dosing during the active study dosing period.
• Patient has history of myocardial infarction, stroke, coronary artery bypass surgery or other coronary, carotid, or cerebral revascularization procedure,unstable angina, or angioplasty within 1 month of Visit 1. - Patient has chronic heart failure defined by New York Heart Association NYHA) Classes III or IV.
• Known clinically significant AV conduction disturbances or arrhythmias
• Patient has unstable hypertension (e.g., sitting systolic blood pressure >160 mm Hg or diastolic >100 mm Hg) at Visit 1.
• Any known clinically important bleeding or platelet disorder.
• Patient has history of ileal bypass, gastric bypass, other significant condition associated with malabsorption.
• Patient is HIV or hepatitis B positive.
• Patients with significantly elevated TSH at Visit 1 may be entered after consultation with and approval by the SPONSOR. Patients with a history of hypothyroidism, who are on a stable dose of thyroxine with normal TSH level at Visit 1 may be included.
• Patients on cyclical estrogen medications (Estrogen Replacement Therapy ERT] or oral contraceptives). Patients on non-cyclical estrogen replacement therapy or Selective Estrogen Receptor Modulator (SERM) may be included, but must be on a stable dose for at least 8 weeks prior.
• Patients with active neoplastic disease which compromises their general health, or who currently require chemotherapy or radiation therapy, or who have completed chemotherapy or radiation therapy within 3 months prior.