Aliskiren Effect on Plaque Progression In Established Atherosclerosis Using High Resolution 3D MRI (ALPINE)

Inclusion Criteria:

- Subjects 45 years and older.

- Male or female subjects are eligible. Female subjects must be either post-menopausal
for one year, surgically sterile, or using effective contraceptive forms such as
barrier method with spermicide or an intra-uterine device. Oral contraceptive use is
disallowed.

- Subjects with established heart or vascular disease defined as:

- Subjects with previous documented MI or CVA AND/OR

- Subjects with PAD (defined as prior evidence of abnormal ABI (<0.9) and/or prior
peripheral intervention/surgery)

- Subjects with bypass surgery and/or stent placement treatment

- LDL cholesterol <130 mg/dL.

- Blood pressures >145/90 mm Hg at visit 2

- Subjects who are eligible and able to participate in the study who consent to do so
after the purpose and nature of the investigation has been clearly explained to them
(written informed consent).

- Subjects who agree to be available for every clinic visit. All study visits will
occur in the morning.

- Subjects on ACE and or ARB therapy will be allowed in the trial provided no dose
adjustments are made during the course of the study.

Exclusion Criteria:

- Uncontrolled hypertension defined as SBP>150mm Hg and/or DBP>95 mmHg at visit 1 and
SBP > 145 mm Hg in visit 2.

- Creatinine >1.5.

- Initiation of new therapy with statins, ACE/ARB, anti-oxidants, calcium channel
blockers, diuretics, β blockers.

- Contraindications to MRI (pacemakers, metallic implants, severe claustrophobia).

- Transient ischemic cerebral attack during the last 6 months.

- Evidence of a secondary form of hypertension, such as coarctation of the aorta,
hyperaldosteronism, unilateral renal disease, or pheochromocytoma.

- Dyslipidemia secondary to other causes. This includes, but is not restricted to
alcoholism, auto-immune disease, nephrotic syndrome, any viral or non viral hepatitis
clinically active within 12 months prior to study entry, obstructive hepatic or
biliary disease, dys- or macroglobulinemia, multiple myeloma, glycogen storage
disease, uncontrolled hypothyroidism or hyperthyroidism, insulin dependent or non
insulin-dependent diabetes mellitus, chronic pancreatitis and porphyria.

- Insulin dependent or non-insulin dependent diabetes mellitus (diabetic subjects may
be enrolled if controlled only with diet).

- Known contraindication, including history of allergy to renin inhibitors.

- Any surgical or medical condition which might significantly alter the absorption,
distribution, metabolism or excretion of any drug. The investigator should be guided
by the evidence of any of the following:

- History of major gastrointestinal tract surgery such as gastrectomy,
gastroenterostomy, or bowel resection.

- Current active or recurrent irritable bowel syndrome (IBS) or history of inflammatory
bowel syndrome. Subjects with a past history of IBS without symptoms for at least 6
months prior to the study start, will be allowed to enter the trial.

- Current active gastritis, ulcers or gastrointestinal or rectal bleeding.

- Subjects that are on any renal replacement therapy ( hemodialysis, peritoneal
dialysis, hemofiltration, renal transplantation)

- Impaired renal function is indicated by serum creatinine levels greater than 1.5 x
ULN at Visit 1. If creatinine is between 1.5 and 2 x ULN, one retest will be
allowed provided all other criteria are fulfilled. Serum creatinine levels must be <
1.5 x ULN at the retest for the subject to be eligible for further study
participation. If serum creatinine is greater than 2 x ULN at any timepoint between
Week-2 and 0, the subject will be excluded from further study participation.

- Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia.

- Sodium depletion.

- History of 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, at the discretion of the investigator,
place the subject at higher risk derived from his/her participation into the study,
or are likely to prevent the subject from complying with the requirements of the
study or completing the trial period.

- History of drug abuse within the last 2 years.

- History of noncompliance to medical regimens, or those subjects unwilling to comply
with the study protocol.

- Participation in any investigational drug trial within one month prior to Visit 1.

- Unwillingness or inability to give informed consent.

- Persons directly involved in the execution of this protocol.