Safety, Tolerability, and Efficacy of Once Daily Amlodipine/Valsartan 5/80 as Compared to Amlodipine/Valsartan 5/40 or to Amlodipine 5 mg Monotherapy in Patients 65 Years of Age and Older With Essential Hypertension

Inclusion criteria

• Provide written informed consent before any assessment was performed.
• Male or female at least 65 years of age.
• Diagnosed as having hypertension:
• At Visit 1/Screening, treatment naïve patients had to have a mean seated SBP ≥ 155 mmHg and < 180 mmHg; patients undergoing washout from their previous antihypertension medication had to have a mean seated SBP <180 mmHg.
• At Visit 2/Single-blind run-in entry, all patients had to have a mean seated SBP ≥ 155 mmHg and < 180 mmHg.
• At Visit 3/Core double-blind treatment period entry, all patients had to have a mean seated SBP ≥ 145 mmHg and < 180 mmHg.
• Ability to communicate and comply with all study requirements including measuring their blood pressure at home, daily as instructed, using the home blood pressure monitor provided by the Sponsor.
• Female patients had to be post-menopausal for at least one year.

Exclusion criteria

• Severe hypertension (mean seated SBP ≥ 180 mmHg and/or a mean seated DBP ≥ 110 mmHg).
• History of secondary hypertension (including primary aldosteronism, renovascular hypertension, pheochromocytoma, etc.).
• Use of three or more antihypertensive drugs. Dual fixed dose combination therapy was considered as two antihypertensive drugs.
• Administration of any agent indicated for the treatment of hypertension after Visit 1, with the permitted exception of those antihypertensive medications requiring tapering down (e.g. beta-blocker and/or clonidine) commencing with Visit 1.
• Known moderate or malignant retinopathy. Moderate was defined as retinal signs of hemorrhage, microaneurysm, cotton-wool spot, hard exudates, or a combination thereof; malignant defined as signs of moderate retinopathy plus swelling of the optic disk.
• Known or suspected contraindications, including history of allergy or hypersensitivity to angiotensin receptor blockers (ARB), calcium channel blockers (CCB), or to drugs with similar chemical structures.
• History of cerebrovascular accident, thrombotic stroke, or transient ischemic attack.
• Significant history of coronary artery disease (CAD) such as any history of myocardial infarction (MI), angina pectoris, and all types of revascularization procedures.
• History of or diagnosis of congestive heart failure Grade II-IV according to the New York Heart Association (NYHA) classification.
• Clinically significant valvular heart disease.
• All patients with Type 1 diabetes mellitus and those patients with Type 2 diabetes mellitus who, in the opinion of the investigator, were not well controlled. Patients who needed oral anti-diabetic medication to adequately control their Type 2 diabetes had to be on a stable dose of oral anti-diabetic medication for at least 4 weeks prior to Visit 1.
• Concomitant potentially life threatening arrhythmia or symptomatic arrhythmia.
• Second or third degree heart block with or without a pacemaker.
• Significant hepatic disease, as demonstrated by any one of the following: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values greater than two times the upper limit of normal at Visit 1, a history of hepatic encephalopathy, a history of esophageal varices, or a history of a portocaval shunt.
• Evidence of renal impairment as determined by any one of the following: glomerular filtration rate (GFR) < 50 ml/min/1.73m2 as measured by the Modification of Diet in Renal Disease (MDRD) formula at Visit 1, a history of dialysis, or a history of nephrotic syndrome.
• History of clinically significant allergies including asthma and/or multiple drug allergies.
• Any surgical or medical condition with the potential to significantly alter the absorption, distribution, metabolism, or excretion of any drug including but not limited to any of the following: history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active or inactive inflammatory bowel syndrome within 1