Amlodipine Versus Valsartan for Improvement of Diastolic Dysfunction Associated With Hypertension
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      Approximately half of hypertensive patients have diastolic dysfunction and diastolic
      dysfunction is associated with development of congestive heart failure and increased
      mortality. The Framingham study reported that 51% of patients with HF have a preserved left
      ventricular (LV) ejection fraction and hypertension is the strongest risk factor for HF with
      preserved ejection fraction, also termed diastolic heart failure. The rates of death and
      morbidity in these patients are as high as in patients with HF and a low LV ejection
      fraction. Hypertensive patients are at increased risk of developing LV hypertrophy and
      myocardial fibrosis, which cause relaxation abnormality and decreased compliance of LV with a
      rise in the LV diastolic pressure. Although diastolic HF associated with hypertension is a
      clinically significant problem, few clinical trials have been conducted and there is no
      proven pharmacological therapy to improve outcomes. 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. The Systolic Blood Pressure Intervention Trial (SPRINT) compared the benefit of
      treatment of systolic blood pressure to a target of less than 120 mmHg with treatment to a
      target of less than 140 mmHg, and recently reported that targeting a systolic blood pressure
      of less than 120 mmHg, as compared with less than 140 mmHg, resulted in lower rates of fatal
      and nonfatal major cardiovascular events and all-cause death. 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. Evaluating the effect of treatments on diastolic dysfunction has been limited by
      difficulties in non-invasive measure of LV diastolic pressure, but recent advances in
      echocardiography have made it possible to assess diastolic dysfunction accurately and
      reproducibly. Thus, 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. To the best of our knowledge, there has
      been no randomized trial to compare the effect of amlodipine versus an ARB on improving
      diastolic dysfunction in hypertensive patients. 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.
    

Intervention name(s): Amlodipine; Valsartan
Intervention type(s): Drug; Drug
Intervention MeSH terms: Amlodipine; Valsartan
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment