Please select the eligibility criteria that correspond to the clinical trial below.
Title: ESCAPE-SHF: A Double-blind, Double-dummy, Randomized, Multicenter, Parallel Group Study to Evaluate the Effects of Aliskiren, Ramipril and Combination Treatment on Plasma Concentration of Angiotensin II in Patients With Decompensated Systolic Heart Failure
Brief Summary: In addition to the blood pressure lowering effects of aliskiren, it may have beneficial effects on blocking the so called RAAS (renin-angiotensin-aldosterone system) at the tissue level. An increase of angiotensin II is associated with progression of heart failure. Although the use of ACE-inhibitors in heart failure shows clinical benefit, an increase in angiotensin II due to an angiotensin II "escape" phenomenon is not desirable. It is not yet known if a direct renin inhibitor can reduce or even prevent the angiotensin II escape phenomenon associated with the use of an ACE-inhibitor. Therefore the study tested the effects of ramipril, aliskiren and the combination of both on levels of angiotensin II in the blood in patients with systolic heart failure


Options:
A: Inclusion Criteria:

* Decompensated systolic heart failure, left ventricular ejection fraction ≤40%
* Brain natriuretic peptide (BNP) level ≥ 100 pg/mL

Exclusion criteria:

* Use of Angiotensin Converting Enzyme(ACE) or Angiotensin Receptor Blocker (ARB) inhibitor treatment following the run-in period or requirement of both treatments
* Acute heart failure secondary to acute myocardial infarction, acute coronary syndrome or new tachyarrhythmia
* Occurrence of unstable angina or myocardial infarction within 12 weeks prior to screening
* History of cardiomyopathy such as postpartum, restrictive, infective, hypertrophic obstructive
* History of right heart failure due to pulmonary disease
* History of untreated second or third degree atrioventricular heart block

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

* Male or female outpatients ≥ 65 years old.
* Patients with essential hypertension with an msSBP ≥ 140 mmHg and \< 180 mmHg, and msDBP \< 110 mmHg at Visits 2 and 3. (Visit 201 was deleted by the Administrative Changes document.)
* Patients must have had a difference in msSBP of ≤ 20 mmHg between Visit 3 and the visit immediately prior to Visit 3.
* Patients who were eligible and able to participate in the study, and who consented to do so after the purpose and nature of the investigation had been explained to them (written informed consent).

Exclusion Criteria:

* History of renal artery stenosis.
* Known Keith-Wagener grade III or IV hypertensive retinopathy.
* History of hypertensive encephalopathy.
* Current diagnosis of heart failure (New York Heart Association Class III-IV).
* History of transient ischemic cerebral attack or cerebrovascular accident within 6 months.
* History of myocardial infarction, bypass surgery, or any percutaneous coronary intervention within 6 months.
* Current unstable angina pectoris. Patients on a stable dose of oral or topical nitrates or beta blockers for angina were acceptable.
* Concurrent potentially life threatening arrhythmia or symptomatic arrhythmia.
* Clinically significant valvular heart disease.
* Concurrent use of any antihypersensitive medications except a stable dose 3 months prior to visit 1 of alpha adrenergic blockers for benign prostatic hypertrophy (e.g., Flomax for BPH), beta blockers for angina, or beta blockers ophthalmic preparations.
C: Inclusion Criteria:

* You are 35 to 65 years of age
* In the past 14 days you have not been treated for hypertension
* In the past 14 days you have not taken more than 2 medications to treat high blood pressure
* You are a woman who is not able to have children or do not use birth control

Exclusion Criteria:

* You are taking more than 2 medications to treat high blood pressure
* You have a history of a stroke, transient ischemic attack (TIA), heart attack, congestive heart failure, coronary artery bypass surgery
* You have Type 1 or 2 diabetes mellitus
* You have an active liver disease, gallbladder disease, or bowel disease
* You are HIV positive
* You have certain types of cancer
* You abuse drug or alcohol
* You have participated in another clinical study in last 4 weeks
D: 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.

Answer: A