Intervention: Aliskiren
Trial phase: Phase 3
ATC code: C09DX02 | C09XA02 | C09XA52 | C09XA53 | C09XA54
SMILES: COCCCOc1cc(C[C@@H](C[C@H](N)[C@@H](O)C[C@H](C(=O)NCC(C)(C)C(N)=O)C(C)C)C(C)C)ccc1OC
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 12
Group description: 150 mg Aliskiren once daily for a period of 4 months.
Eligibility criteria:
Inclusion Criteria:

Age > 18 years old
More than two of the following cardiovascular risk factors (determined by prescreen phone call): family history of cardiovascular disease, physical inactivity/sedentary lifestyle, obesity or overweight, family history of diabetes mellitus or hypertension, total cholesterol > 200 mg/dL, LDL > 130 mg/dL, HDL < 50 mg/dL, smoking, stress, or Triglycerides > 150 mg/dL
Demonstrated endothelial dysfunction (reactive hyperemia - EndoPAT score < 2.0) at time of screening

Exclusion Criteria:

Serum potassium > 5.0 mmol/L documented at any time prior to the study
History of any cardiovascular event (stroke, transient ischemic attack (TIA), myocardial infarction (MI), unstable angina, coronary artery bypass grafting (CABG), percutaneous coronary intervention, hospitalization due to heart failure) during the 3 months prior to the study
Hypertension or hypotension (at Randomization): any patient with Mean Seated Systolic Blood Pressure (msSBP) ≥ 170 mmHg, msSBP < 100 mmHg or Mean Seated Diastolic Blood Pressure (msDBP) ≥ 110 mmHg
Congestive heart failure New York Heart Association (NYHA) class III and IV
Concomitant treatment with two (2) or more renin-angiotensin-aldosterone system blocking agents, e.g. Angiotensin Converting Enzyme Inhibitor (ACEI), Angiotensin II receptor blockers (ARB) or aldosterone-antagonist
Unstable serum creatinine
Second (II) or third (III) degree heart block without a pacemaker
Concurrent potentially life threatening arrhythmia or other uncontrolled arrhythmia
Clinically significant valvular heart disease
Known renal artery stenosis

Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of the study drugs including, but not limited to, any of the following:

History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase
Evidence of hepatic disease as determined by a history of hepatic encephalopathy, a history of cirrhosis, esophageal varices, or a history of portocaval shunt
History of malignancy other than basal cell skin cancer within the past five years
Any concurrent life threatening condition with a life expectancy less than 2 years
History or evidence of drug or alcohol abuse within the last 12 months
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
History of hypersensitivity to any of the study drugs or to medications belonging to the same therapeutic class as the study drugs as well as known or suspected contraindications to the study drugs
History of noncompliance to medical regimens or unwillingness to comply with the study protocol
Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety
Persons directly involved in the execution of this protocol
Pregnant or nursing (lactating) women
Women of Child-Bearing Potential (WOCBP) unless postmenopausal for at least one year, surgically sterile or using effective methods of contraception as defined by local Health Authorities