Efficacy and Safety of Aliskiren and Valsartan Versus Placebo in Patients Stabilized Following an Acute Coronary Syndrome

Phase 2

Completed

Interventions: Drug: Aliskiren 300 mg
Drug: Valsartan 320 mg
Drug: Aliskiren/valsartan 300/320 mg
Drug: Placebo

Brief Summary: The purpose of this study is to test the hypothesis that the inhibition of the renin-angiotensin-aldosterone system (RAAS) with the angiotensin receptor blocker valsartan or the renin antagonist aliskiren will improve ventricular hemodynamics, as reflected by a greater reduction in levels of N-terminal proB-type natriuretic peptide (NT-proBNP) compared to placebo in subjects stabilized following acute coronary syndrome (ACS) who are determined to be at high risk due to an elevated concentration of natriuretic peptides.

Recruitment & Eligibility

Inclusion Criteria

Male or female outpatients 18 years old or older
Subjects who are hospitalized for ischemic chest discomfort at rest lasting at least 10 minutes and consistent with cardiac ischemia
Final diagnosis of acute coronary syndrome
Elevated concentrations of natriuretic peptide 3-10 days after admission for their qualifying acute coronary syndrome event

Exclusion Criteria

Known or suspected contraindications, including history of allergy or hypersensitivity to angiotensin receptor blockers (ARBs), renin antagonists, or to drugs with similar chemical structures.
Presence of clinically overt heart failure
Known evidence of left ventricular systolic dysfunction
Percutaneous coronary intervention (PCI) less than 24 hours before randomization.
Patients on chronic ACEI or ARB therapy for whom therapy with an ACEI or ARB is clinically required with no reasonable alternative therapy available.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Arm && Interventions

Group	Intervention	Description
Aliskiren 300 mg	Aliskiren 300 mg	Following 1 week of treatment with 75 mg of aliskiren (tablets), patients in this arm were titrated up to 150 mg of aliskiren; 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.
Valsartan 320 mg	Valsartan 320 mg	Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study.
Aliskiren/valsartan 300/320 mg	Aliskiren/valsartan 300/320 mg	Following 1 week of treatment with 80 mg of valsartan (capsules), patients in this arm were titrated up to 160 mg of valsartan; 1 week later they were titrated up to 320 mg valsartan for the remainder of the study. Beginning with Week 4, in addition to 320 mg valsartan, patients were treated with 75 mg of aliskiren (tablets); 1 week later patients were titrated up to 150 mg of aliskiren and 1 week later they were titrated up to 300 mg aliskiren for the remainder of the study.
Placebo	Placebo	Placebo tablets and capsules

Primary Outcome Measures

Name	Time	Method
Change From Baseline in N-terminal proB-type Natriuretic Peptide (NT-proBNP) at Week 8	Baseline to Week 8	Blood samples for the measurement of NT-proBNP were collected, processed, and shipped to the TIMI Biomarker Core Laboratory, Boston MA for storage and analysis. The change from baseline to Week 8 was expressed as the geometric mean of the ratio: Week 8/Baseline.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in B-type Natriuretic Peptide (BNP) at Week 8	Baseline to Week 8	Blood samples for the measurement of BNP were collected, processed, and shipped to the TIMI Biomarker Core Laboratory, Boston MA for storage and analysis. The change from baseline to Week 8 was expressed as the geometric mean of the ratio: Week 8/Baseline.
Percentage of Patients With a Cardiac Event	Baseline to Week 8	A cardiac event was defined as at least one of the following events: Cardiovascular death, recurrent myocardial infarction (MI), or hospitalization for congestive heart failure (CHF), all to be confirmed by adjudication.
Percentage of Patients With a Composite Clinical-biochemical Event	Baseline to Week 8	A composite clinical-biochemical event was defined as at least one of the following events: cardiovascular death confirmed by adjudication, recurrent MI confirmed by adjudication, hospitalization for CHF confirmed by adjudication, and/or NT-proBNP =\> 200 pg/mL.