Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 104 Week, Randomized, Double Blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy of Aliskiren on the Progression of Atherosclerosis in Patients With Coronary Artery Disease When Added to Optimal Background Therapy
Brief Summary: The study will assess the change in coronary atherosclerotic disease as determined by intravascular ultrasound (IVUS) for aliskiren compared to placebo when given in addition to standard therapy in patients with coronary artery disease (CAD) and a blood pressure in the pre-hypertensive range.


Options:
A: Core Study Inclusion Criteria:

* Male or female patients 18 years and older.
* Patients within 7-42 days of an acute myocardial infarction associated with left ventricular systolic dysfunction.
* Documented left ventricular systolic dysfunction associated with the qualifying acute myocardial.
* Patients must be on stable doses of the following concomitant medications for at least 2 weeks prior to Visit 1 unless contraindicated due to intolerance:

  * A Beta-blocker
  * An Anti-platelet agent
  * A Statin
  * An evidence-based dose of an Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB) but not both.
* Qualifying Echocardiogram at Visit 1:

Core Study Exclusion Criteria:

* Patients requiring both Angiotensin Converting Enzyme Inhibitor (ACEI) and Angiotensin Receptor Blocker (ARB) combination therapy at V1 or any time during the study.
* Severe refractory hypertension defined as mean sitting systolic blood pressure (MSSBP) ≥ 180 mmHg and/or mean sitting diastolic blood pressure (MSDBP) ≥ 110 mmHg) at Visit 2.
* Cardiogenic shock or systolic BP \< 100 mmHg or diastolic \< 60 mmHg within the 24 hours prior to Visits 1 or 2
* Estimated Glomerular Filtration Rate (eGFR) \< 30 ml/min/1.73m2 using the MDRD formula at Visit 1.
* Stroke or transient ischemic event (TIA) within 6 months of Study Visit 1

Extension Study Inclusion Criteria:

* Male or female patients who completed the core study through Visit 10 while on double-blind study drug
* Patients who were able to participate in the study, and who consented to do so after the purpose and nature of the study had been clearly explained to them (written informed consent)

Extension Study Exclusion Criteria:

* New York Heart Association (NYHA) class IV Congestive Heart Failure at Visit 1 (Core study Visit 10)
* Symptomatic hypotension or reported systolic blood pressure (BP) \< 90 mmHg within 24 hours prior to Visit 1 (Core study Visit 10)
* Known Estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min/1.73m\^2 using the Modification of Diet in Renal Disease (MDRD) formula at Visit 1 (Core study Visit 10)
* Pregnant or nursing (lactating) women, where pregnancy was defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/mL)
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant Unless post-menopausal or using an acceptable method of contraception
* Any surgical or medical condition that in the opinion of the investigator may place the patient at higher risk from his/her participation in the study or was likely to prevent the patient from complying with the requirements or completing the study

Other protocol-defined inclusion/exclusion criteria applied
B: 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
C: Inclusion Criteria:

* Patients with CAD who have blood pressure in the pre-hypertensive range defined as a msSBP ≥ 125 and ≤ 139mmHg and a msDBP \< 90mmHg.
* Patients with or without current treatment for hypertension
* Angiographic evidence of coronary artery disease
* At least 2 qualifying Cardiovascular risk factors at Visit 1

Exclusion Criteria:

* Baseline IVUS determined unacceptable
* Patients requiring treatment with disallowed study medications
* Patients with clinically significant heart disease
* Previous or current diagnosis of heart failure (NYHA Class IV) or a documented left ventricular ejection fraction of \< 25%
* Patients requiring treatment with any 2 of the following classes of medication at Visit 1 or Visit 2:

  * Angiotensin converting enzyme inhibitors
  * Angiotensin receptor blockers
  * aldosterone receptor blockers or a direct renin inhibitor.
* Other conditions may apply
D: Inclusion Criteria:

* Male and/or female subjects between the ages of 30-80 years with a diagnosis of type 2 diabetes (World Health Organization criteria)
* Body mass index (BMI) within the range of 20 and 32.
* Incipient or overt diabetic nephropathy (urinary albumin excretion ≥ 100 but ≤ 2000 mg/day).
* Glomerular filtration rate (GFR) ≥ 40 ml/min documented in the last 4 months prior to randomization
* To be eligible for randomization, patients must fulfill the following criteria:

  1. Patients on ongoing hypertensive therapy must have a blood pressure ≥ 135/85 mmHg but lower than 170/105 mmHg at Visit 2 (Day -1) AND patients must be on stable antihypertensive medications for at least 8 weeks prior to Visit 2 (run-in period).
  2. Newly diagnosed hypertensive patients must have a blood pressure ≥ 135/85 mmHg but lower than 170/105 mmHg at Visit 2 (Day -1).
* Patients must be on stable hypoglycemic medications for at least 8 weeks prior to Visit 2 (Day -1).
* Patients must be willing and medically able to discontinue all angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), aldosterone receptor antagonist and potassium sparing diuretic medications for the duration of the study.
* Female patients must be postmenopausal, have had a bilateral oophorectomy, or have been surgically sterilized or hysterectomized at least 6 months prior to screening.
* Oral body temperature within the range of 35.0-37.5 °C
* Able to provide written informed consent prior to study participation.
* Able to communicate well with the investigator and comply with the requirements of the study.

Exclusion Criteria:

* Severe hypertension, Grade 3 World Health Organization (WHO) classification (mean sitting diastolic blood pressure \[MSDBP\] ≥ 110 mmHg and/or mean sitting systolic blood pressure \[MSSBP\] ≤ 180 mmHg)
* Acetylsalicylic acid (ASA) treatment \> 1 g/day or regular use of nonsteroidal anti-inflammatory drugs (NSAIDs)
* Kidney disease not caused by diabetes or hypertension
* Serum potassium \< 3.5 or \> 5.1 mEq/L
* GFR \< 40 ml/min/1.73m2 as measured by the Modification of Diet in Renal Disease (MDRD) formula
* Serum albumin \< 2.0 mg/dL
* History of hypertensive encephalopathy or cerebrovascular accident in the last 12 months prior to Visit 1
* Transient ischemic cerebral attack during the 6 months prior to Visit 1
* Current diagnosis of heart failure (New York Heart Association \[NYHA\] Class II-IV)
* History of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any percutaneous coronary intervention (PCI) during the 6 months prior to Visit 1
* Second or third degree heart block without a pacemaker
* Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia
* Clinically significant valvular heart disease
* Type 1 diabetes mellitus
* Uncontrolled type II diabetes mellitus; hemoglobin subtype A1C (HbA1C) \> 11%
* History of malignancy including leukemia and lymphoma (but not basal cell skin carcinoma) within the past five years
* Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation.
* Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing.
* Significant illness within the two weeks prior to dosing.
* Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of study drugs including, but not limited to, any of the following:

  * History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
  * Currently active or previously active inflammatory bowel disease during the 12 months prior to Visit 1
  * Currently active gastritis, duodenal or gastric ulcers, or gastrointestinal/rectal bleeding during the 3 months prior to Visit 1.
  * Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase
  * Evidence of hepatic disease, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portacaval shunt
  * Current treatment with cholestyramine or colestipol resins
* History of immunocompromise, including a positive test result.
* History of a positive hepatitis B surface antigen (HBsAg) or hepatitis C test result.
* History of drug or alcohol abuse within the 12 months prior to dosing.
* Persons directly involved in the execution of this protocol.
* Any condition that, in the opinion of the investigator or the Novartis medical monitor, would jeopardize the evaluation of efficacy or safety
* History of noncompliance to medical regimens or unwillingness to comply with the study protocol
* Known or suspected contraindications to the study medications, including history of allergy to ACE inhibitors and/or to thiazide diuretics or other sulfonamide derived drug
* Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study
* Use of any prescription drug or over-the-counter (OTC) medication which is prohibited by the protocol.
* Patients who previously participated in any aliskiren study.

Other protocol-defined inclusion/exclusion criteria may apply.

Answer: C