The Effects of Systolic Blood Pressure Lowering on Diastolic Function Using Valsartan + Amlodipine in Patients With Hypertension and Diastolic Dysfunction
The Effects of Systolic Blood Pressure Lowering on Diastolic Function Using Valsartan + Amlodipine in Patients With Hypertension and Diastolic Dysfunction
The purpose of this study is to determine the effects of treatment with valsartan +
 amlodipine to a target systolic blood pressure (SBP)<130 mmHg compared to the Joint National
 Commission on the Treatment of Hypertension 7 recommended target SBP of <140 mmHg on the
 intrinsic diastolic properties of the myocardium in patients with hypertension and
 echocardiographic evidence of diastolic dysfunction.
Inclusion Criteria:

 -  Age 45 years or older

 -  Male and female patients are eligible. Female patients must be post-menopausal for one
 year, surgically sterile, or using effective contraceptive methods such as a double
 barrier method with spermicide, an intra-uterine device, or hormonal contraceptives.
 Post-menopausal women on a stable dose of hormone replacement therapy (HRT) for at
 least three (3) months prior to the screening visit are eligible for the study.

 -  Uncontrolled systolic hypertension on a maximum of two (2) antihypertensive
 medications at the time of screening.

 -  Echocardiographic ejection fraction ≥50% and evidence of diastolic dysfunction.

 -  Provide written informed consent to participate in the study prior to any screening or
 study procedures

 -  Have the ability to communicate well and comply with all study requirements

 Exclusion Criteria:

 -  Severe hypertension defined as a MSSBP >200 mmHg and/or MSDBP >120 mmHg.

 -  History of a secondary cause of hypertension including but not limited to: coarctation
 of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis,
 Cushing's disease, pheochromocytoma, polycystic kidney disease, etc.

 -  Ejection fraction <50 %

 -  History of stroke, transient ischemic attack, myocardial infarction, coronary artery
 bypass graft surgery, or unstable angina pectoris within 6 months of screening

 -  Presence of clinically significant ventricular or supraventricular arrhythmias (e.g.
 atrial fibrillation/flutter)

 -  History of congestive heart failure

 -  History of diabetes mellitus

 -  History of renal impairment with serum creatinine >2.0 mg/dL at screening, history of
 dialysis, or history of nephritic syndrome

 -  Antihypertensive therapy with three (3) or more medications at the time of screening

 -  Active and/or treated malignancy of any organ system within twelve (12) months of
 enrollment, with the exception of localized basal cell carcinoma of the skin

 -  Pregnant or nursing (lactating) women, where pregnancy is 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 (WOCBP), defined as all women physiologically capable
 of becoming pregnant, including women whose career, lifestyle, or sexual orientation
 precludes intercourse with a male partner and women whose partners have been
 sterilized by vasectomy or other means, UNLESS they meet the following definition of
 post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of
 spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post surgical
 bilateral oophorectomy with or without hysterectomy OR are using one or more of the
 following acceptable methods of contraception: barrier method with spermicidal agent,
 an intrauterine device, hormonal contraceptives, or total abstinence at the discretion
 of the investigator in cases where the age, career, lifestyle, or sexual orientation
 of the patient ensures compliance. Periodic abstinence (e.g., calendar, ovulation,
 symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of
 contraception. Reliable contraception should be maintained throughout the study

 -  Any surgical or medical condition which might 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 active inflammatory bowel syndrome within 12 months
 prior to Visit 1, currently active gastritis, ulcers, or gastrointestinal/rectal
 bleeding, or urinary tract obstruction regarded as clinically meaningful by the
 investigator

 -  Pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury
 within 12 months prior to Visit 1

 -  Any serum AST or ALT elevation two (2) times the upper limit of normal

 Other protocol-defined inclusion/exclusion criteria may apply