A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People
Condition: Cardiovascular Events
Intervention: Aliskiren; Amlodipine; Hydrochlorothiazide (HCTZ); Placebo for Aliskiren; Placebo for Amlodipine; Placebo for Hydrochlorothiazide (HCTZ)
Intervention description: Aliskiren 150/300 mg once daily; Amlodipine 5 mg; HCTZ 12.5/25 mg; Placebo for Aliskiren 300 mg; Placebo for Amlodipine; Placebo for HCTZ 12.5/25 mg
Intervention MeSH terms: Amlodipine; Hydrochlorothiazide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 2336.0
Sex: All
Minimum age: 65 Years
Healthy volunteers: No
Keywords: Aliskiren; Elderly; Major Cardiovascular Events; Effect of aliskiren-based regimen on major CV events (composite of CV death, non-fatal MI, non-fatal stroke and significant heart failure) in the elderly

Summary:

      This study was planned to provide new information regarding the role of aliskiren (with or
      without additional therapy with a diuretic or a Calcium channel blockers (CCB)) in elderly
      individuals (≥ 65 years) with systolic blood pressure (SBP) 130 to 159 mmHg, in preventing
      major cardiovascular (CV) events and on global measures of physical, executive and cognitive
      function.
    

Eligibility criteria:

        Inclusion Criteria:

        Systolic blood pressure 130 - 159 mmHg with any one of the following (1, 2 or 3):

          1. Men and women aged ≥ 65 years if they have at least one of the following: (secondary
             prevention) Coronary heart disease

               -  Previous myocardial infarction or

               -  Stable angina or unstable angina with documented multi-vessel coronary artery
                  disease, > 50% stenosis in at least 2 major coronary arteries on coronary
                  angiography, or positive stress test (ECG or nuclear perfusion scintogram), or

               -  Multi-vessel PCI, or

               -  Multi-vessel CABG surgery > 4 years prior to informed consent, or with recurrent
                  angina or ischemia following surgery Stroke/TIA Previous documented stroke or
                  documented TIA < 1 year before informed consent Peripheral artery disease

               -  Previous limb bypass surgery or percutaneous transluminal angioplasty, or

               -  Previous limb or foot amputation, or

               -  History of intermittent claudication, with an ankle:arm BP ratio ≤ 0.80 on at
                  least one side, or significant peripheral artery stenosis (> 50%) documented by
                  angiography or non-invasive testing

               -  Diabetes mellitus: High-risk diabetics with evidence of end-organ damage

          2. Men and women aged ≥ 65 years with no history of CVD, and with at least 1 CV risk
             factor (primary prevention):

               -  History of dyslipidemia, defined as LDL cholesterol > 3.5 mmol/L (135 mg/dL) or
                  HDL< 1.3 mmol/L (50 mg/dL) in women or < 1.0 mmol/L (39 mg/dL) in men or total
                  cholesterol/HDL ratio > 5

               -  History of current or recent smoking (regular tobacco use within 5 years)

               -  Abdominal adiposity defined as waist/hip ratio ≥ 0.90 in women and ≥ 0.95 in men

               -  History of dysglycemia defined as impaired fasting glucose (IFG - fasting plasma
                  glucose 5.6 to 6.9 mmol/L [101 to 124 mg/dL]), or impaired glucose tolerance (IGT
                  - fasting plasma glucose < 7 mmol/L [126 mg/dL] but 2 hour glucose 7.8 to 11.0
                  mmol/L [140 to 198 mg/dL]) or type 2 diabetes

               -  Renal dysfunction: eGFR< 60 ml/min/1.73m2 but > 30 ml/min/1.73m2 (MDRD formula)
                  and/or microalbuminurea/macroalbuminurea

               -  Clinical evidence of left ventricular hypertrophy

          3. Men and women aged ≥ 70 years if they do not have any of the above (primary
             prevention)

        Exclusion Criteria:

          1. Current treatment with aliskiren, an ACE-inhibitor, an ARB or an aldosterone
             antagonist and unable to discontinue this therapy in those without clinical vascular
             disease. Individuals with CVD or type 2 diabetes and/or renal dysfunction may receive
             an ACE-inhibitor or an ARB, but not both, contraindications to Aliskiren, Amlodipine
             or Hydrochlorothiazide.

          2. Use of both thiazide diuretic and amlodipine or another calcium channel blocker.
             Patients on only one of these two classes of drugs are eligible

          3. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood
             pressure ≥ 100 mmHg)

          4. Symptomatic heart failure, requiring the use of loop diuretics

          5. Hemodynamically significant primary valvular or outflow tract obstruction (e.g. aortic
             or mitral valve stenosis, asymmetric septal hypertrophy, malfunctioning prosthetic
             valve). Constrictive pericarditis. Complex congenital heart disease.

          6. Acute stroke < 3 months or TIA ≤ 7 days before informed consent, acute coronary
             syndrome < 1 months before informed consent

          7. Planned cardiac surgery or angioplasty < 3 months after informed consent or having had
             the procedure < 3 months before informed consent

          8. Severe renal impairment eGFR ≤ 30 ml/min/1.73m2 (MDRD formula); known renal artery
             stenosis ; serum potassium ≥ 5.3 mmol/L

          9. Chronic liver disease (i.e. cirrhosis, esophageal varices, portocaval shunt or
             persistent hepatitis) or abnormal liver function, i.e., alanine transaminase (ALT) or
             AST > 3x upper limit of normal (ULN)

         10. Concurrent treatment with cyclosporine or quinidine; chronic use of non-steroidal
             anti-inflammatory drug (NSAIDs) or cyclooxygenase-2 (COX 2) inhibitors in patients
             with eGFR < 60 ml/min/1.73m2 (MDRD formula)

         11. History of malignancy of any organ system (other than localized basal cell carcinoma
             of the skin), treated or untreated, within the past 5 years regardless of whether
             there is evidence of local recurrence or metastases

         12. Other serious condition(s) likely to interfere with study participation or with the
             ability to complete the study. Significant psychiatric illness, senility, dementia,
             alcohol or substance abuse, which could impair the ability to provide informed consent
             and to adhere to the study procedures