A 36 week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of aliskiren on the prevention of left ventricular remodeling in high risk post-acute myocardial infarct patients when added to optimized standard therapy

This study is designed to provide surrogate marker data [change in left
ventricular end systolic volume (LVESV) as determined by echocardiography] for
the efficacy and safety of aliskiren compared to placebo when given in addition
to optimized standard therapy in high-risk post-AMI patients. This trial will
serve as a proof-of-concept study to plan and potentially conduct future
clinical outcomes studies in this patient population.

The primary objective of this trial is to demonstrate that aliskiren 300 mg, in
addition to standard therapy, has superior efficacy compared to placebo in
reducing the primary index of adverse cardiac remodeling (defined as the change
in LVESV from baseline to end of study) in patients after high risk acute
myocardial infarction.
The secondary objectives of this trial are to evaluate the effect of aliskiren
compared to placebo on:
* a composite outcome of CV death, hospitalization for heart failure, or a
reduction in ejection fraction greater than 6 units (absolute percentage points)
* a composite outcome of CV death, hospitalization for heart failure, recurrent
myocardial infarction, stroke or resuscitated sudden death
* change in left ventricular ejection fraction (LVEF) between baseline and end
of study
* change in left ventricular end-diastolic volume (LVEDV) between baseline and
end of study
* RV and LV volumes, LVEF, and myocardial infarct related scarring as
determined by contrast enhanced MRI (in a subset of patients)
* overall safety and tolerability in combination with standard therapy in
patients post acute myocardial infarction.

This is a multicenter, multinational, randomized, double-blind,
placebo-controlled, parallel-group study to evaluate the efficacy and safety of
aliskiren on the prevention of left ventricular remodeling in high risk
post-AMI patients when added to optimized standard therapy. Patients who have
a documented AMI will be evaluated for left ventricular dysfunction. Patients
who meet echocardiographic criteria for reduced LVEF and who are on optimized
background therapy will be randomized to aliskiren or placebo with
stratification based on the patients* baseline (Visit 2) use of aldosterone
receptor antagonist medications. The purpose of stratification is to ensure
equal assignment of patients to each stratum [stratum 1 will represent patients
on baseline (Visit 2) aldosterone receptor blockers while stratum 2 will
represent patients not on baseline (Visit 2) aldosterone receptor blockers] in
the 2 treatment groups. There are no constraints on the number of patients in
each stratum. Study medication will be administered for 36 weeks, followed by
assessments for adverse cardiac remodeling.

There are two treatment groups:
1) Aliskiren 75 mg, force-titrated via 150 mg Aliskiren to 300 mg Aliskiren (in
a period of 2 weeks)
2) Placebo

Risks are possible side effects of study medicine or another medicine, and
those of taking blood. The most common side effects reported in research
studies to date with aliskiren were:
* Headache
* Dizziness
* Fatigue
* Abdominal pain
* Nausea
* Diarrhea
Problems or side effects that are not now known could also occur.

10 study visits will be payed to the medical center. The tests done at each
study visit are standard medical tests. The most unpleasant is often having
blood samples taken, which will be done every visit. The risks of taking blood
may include pain and/or bruising.

The blood pressure cuff may also cause discomfort or bruising to the upper arm.
Bloodpressure will be taken every visit. Physical examinations (3 times),
electrocardiograms (ECGs; 3 times) and echocardiograms (ECHO; 2 times) are
routine procedures in clinical practice and present practically no risk to the
patient.