Amlodipine Versus Valsartan for Improvement of Diastolic Dysfunction Associated With Hypertension

• Status: Completed
• Trial end date: 2020-01-06
• Target enrollment: 0
• Participant gender: All

Summary

Hypertensive patients are at increased risk of developing LV hypertrophy and myocardial fibrosis, which cause diastolic dysfunction. Because the activation of rennin-angiotensin-aldosterone system (RAAS) has been shown to induce LV hypertrophy and myocardial fibrosis, the RAAS may play a central role in the pathogenic process from hypertension to diastolic HF. Inhibitors of RAAS have been considered as a treatment option for these patients, and the angiotensin receptor blockers (ARB) have been of interest because they antagonize the effects of angiotensin II more completely. However, the Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) trial reported that treatment with irbesartan did not reduce the risk of death or hospitalization for cardiovascular causes among 4,128 patients who had HF with a preserved LV ejection fraction. The degree of improvement of diastolic dysfunction was associated with the extent of systolic blood pressure reduction, whether a RAAS inhibitor or non-RAAS blood pressure lowering was used. Amlodipine is a potent and well-tolerated calcium channel blocker, and seems to be appropriate for achieving more aggressive systolic blood pressure target and improving diastolic dysfunction in hypertensive patients, because amlodipine is clinically very useful for controlling systolic blood pressure. Assessment of diastolic function by echocardiography will be helpful to determine whether addition of amlodipine or an ARB to standard therapy is more beneficial to hypertensive patients with diastolic dysfunction. The investigators hypothesize that amlodipine added to standard therapy will be superior to valsartan in improving diastolic dysfunction by lowering systolic blood pressure more effectively in hypertensive patients, and try to examine this hypothesis in a prospective, open-label, randomized comparison study using blinded echocardiographic evaluation for end point.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Asan Medical Center
• Collaborator: Yuhan Corporation
• Treatments: Amlodipine; Valsartan

Criteria

Inclusion Criteria:

• Controlled hypertension: systolic BP < 150 and diastolic BP < 90 mmHg in persons aged 60 years or older, systolic BP < 140 and diastolic BP < 90 mmHg in persons 40 through 59 years according to the JNC 8th guideline

• Evidence of diastolic dysfunction showing E/E' > 10

• The patient agrees to the study protocol and the schedule of clinical and echocardiographic follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site

Exclusion Criteria:

• Unwillingness or inability to comply with the procedures described in this protocol

• Planned cardiac surgery or planned major non-cardiac surgery within the study period.

• Stroke or coronary revascularization in the past 6 months.

• Clinically significant pulmonary disease.

• Untreated hyperthyroidism, or hypothyroidism.

• A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in the past 3 years or current treatment for the active cancer.

• Female of child-bearing potential who do not use adequate contraception and women who are pregnant or breast-feeding

• Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the Investigator, would preclude safe completion of the study.

• LV ejection fraction < 50%.

• Significant renal disease manifested by serum creatinine > 2.5 mg/dL

• Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST > 3 times upper limit of normal).

• History of intolerance to ARB or amlodipine.

• Hypertrophic or restrictive cardiomyopathy.

• Moderate or severe valvular disease.

• Constrictive pericarditis

• Atrial fibrillation with a heart rate > 120/min.

• Sitting systolic BP < 100 mmHg