Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbidity-mortality in Patients With Chronic Heart Failure
Condition: Chronic Heart Failure
MeSH terms: Heart Failure
Intervention: Enalapril; Aliskiren
Intervention description: Enalapril 10 mg film-coated tablet and administered orally.; Aliskiren 150 mg titrated to 300 mg film-coated tablet and administered orally.
Intervention MeSH terms: Enalapril
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 7064.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic Heart Failure; Cardiovascular death; CHF hospitalization; morbi-mortality trial; outcome study; endpoint driven; plasma renin activity; renin angiotensin aldosterone system; direct renin inhibitors; BNP; KCCQ; eGFR; (NYHA class II to IV) with elevated; BNP and reduced LVEF

Summary:

      The study will evaluate the efficacy and safety of both aliskiren monotherapy and
      aliskiren/enalapril combination therapy as compared to enalapril monotherapy, on morbidity
      and mortality in patients with chronic heart failure (NYHA Class II - IV.
    

Eligibility criteria:

        Inclusion Criteria

        Patients eligible for inclusion in this study had to fulfill all of the following criteria:

          1. Patients ≥ 18 years of age, male or female.

          2. Patients with a diagnosis of chronic heart failure (NYHA

             Class II - IV):

               1. LVEF ≤ 35% at Visit 1 (local measurement, within the past 6 months assessed by
                  echocardiography, multiple uptake gated acquisition scan (MUGA), computerized
                  tomography(CT) scan, magnetic resonance imaging (MRI) or ventricular angiography)

               2. Elevated BNP or NT-proBNP at Visit 1:

             BNP ≥ 150 pg/mL (or BNP ≥ 100 pg/mL and unplanned hospitalization for HF within the
             last 12 months prior to Visit 1) (according to local measurement). OR NT-proBNP ≥ 600
             pg/mL (or NT-proBNP ≥ 400 pg/mL and unplanned hospitalization for HF within the last
             12 months prior to Visit 1) (according to local measurement).

          3. Patients had to be treated with an ACEI at a stable dose enalapril 10 mg daily at
             least or any other ACEI, e.g. ramipril, quinapril, lisinopril, fosinopril,
             perindopril, trandolapril; based on equivalent doses, for at least 4 weeks prior to
             Visit 1

          4. Patients had to be treated with a beta-blocker, unless contraindicated or not
             tolerated, at a stable dose for at least 4 weeks prior to visit 1 (for patients not on
             target dose, according to local guidelines, or in absence of that medication, the
             reason should be documented).

          5. Written informed consent to participate in the study and ability to comply with all
             requirements.

        Exclusion Criteria

        Patients with any of the following were to be excluded from participation in the study:

          1. History of hypersensitivity to any of the study drugs including history or allergy to
             ACEIs as well as known or suspected contraindications to the study drugs or previous
             history of intolerance to high doses of ACEIs during up- titration process.

          2. Patients treated concomitantly with both an ARB and an aldosterone antagonist in
             addition to study drug at Visit 1.

          3. Current acute decompensated HF (defined as an acute exacerbation of a chronic heart
             failure status manifested by typical signs and symptoms of HF like dyspnea, fatigue
             etc., that may require IV therapy with diuretics, vasodilators and/or inotropic
             drugs).

          4. Symptomatic hypotension and/or less than 95 mmHg systolic blood pressure (SBP) at
             Visit 1 and/or less than 90 mmHg SBP at Visit 4.

          5. Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or major
             vascular surgery, percutaneous coronary intervention (PCI) or carotid angioplasty,
             within the past 3 months prior to Visit 1.

          6. Coronary or carotid artery disease likely to require surgical or percutaneous
             intervention within the 6 months after Visit 1.

          7. Right heart failure due to severe pulmonary disease.

          8. Patients with Diabetes Mellitus.