Comparision of Blood Pressure Variability Between Amlodipine and Losartan
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 4

Summary: 
      Blood pressure (BP) is believed to be a major determinant of vascular disease, and BP
      lowering is the most important goal in hypertension treatment. Thus, clinical guidelines for
      hypertension are mainly focused on lowering mean BP. However, despite an increasing incidence
      of stroke with age, the association between systolic BP (SBP) and the risk of stroke
      decreases with age. This disparity highlights a gap in the link between BP and
      vascular-related diseases (i.e., stroke). In clinical practice, visit-to-visit fluctuations
      in BP have been largely ignored and are thought to be an unreliable finding, even though this
      phenomenon is frequently observed. Rothwell et al. demonstrated that the visit-to-visit
      variability in SBP was a more powerful independent predictor of stroke than mean SBP, and
      that an increased residual variability in SBP in treated hypertensive patients was also a
      strong predictor of stroke and coronary events.

      Recently updated (2011) hypertension guidelines from the National Institute for Health and
      Clinical Excellence (NICE) recommend an angiotensin converting enzyme inhibitor (ACEi) [or
      angiotensin II receptor blocker (ARB)] and calcium-channel blocker (CCB) as a first line
      drug. Although the significance of BP variability (BPV) has been illustrated, the main focus
      of the current guidelines is to reduce systolic and diastolic BP, not BPV.

      In the X-CELLENT study, a CCB (amlodipine) and thiazide-like diuretic drug (indapamide
      sustained-release) led to a significant reduction in BPV, compared to an ARB (candesartan).
      In addition, the CCB showed the most effective reduction in systolic BPV among the
      antihypertensive drug class in a meta-analysis. However, there are no direct comparison
      studies of a CCB and ARB on BPV. Thus, we aim to compare the systolic BPV effects of a CCB
      versus an ARB in essential hypertensive patients. The primary hypothesis is that an ARB is
      not inferior to a CCB in the reduction of the systolic BPV standard deviation (SD) in
      essential hypertensive patients.
    


Intervention name(s): Amlodipine; Losartan
Intervention type(s): Drug; Drug
Intervention description(s): Eligible subjects will be randomized 1:1 to either an amlodipine or a losartan group by a computer-generated random number table. For patients who fail to respond to 5 mg amlodipine, the dose will be titrated up to 10 mg amlodipine. At subsequent visits, additional antihypertensive therapy (hydrochlorothiazide) will be added if systolic (>140 mmHg) or diastolic (>90 mmHg) BP is inadequate. Study drugs are administered once a day for 24 weeks. The dose will be titrated up if SBP is over 90 mmHg or there are no symptoms of hypotension (syncope, loss of consciousness, or orthostatic hypotension). If up-titration is not tolerable, because of side effects or hypotension, the previous dose will be administered as the final tolerable dose.; Eligible subjects will be randomized 1:1 to either an amlodipine or a losartan group by a computer-generated random number table. For patients who fail to respond to 50 mg losartan, the dose will be titrated up to 100 mg losartan. At subsequent visits, additional antihypertensive therapy (hydrochlorothiazide) will be added if systolic (>140 mmHg) or diastolic (>90 mmHg) BP is inadequate. Study drugs are administered once a day for 24 weeks. The dose will be titrated up if SBP is over 90 mmHg or there are no symptoms of hypotension (syncope, loss of consciousness, or orthostatic hypotension). If up-titration is not tolerable, because of side effects or hypotension, the previous dose will be administered as the final tolerable dose.
Other intervention name(s): Norvasc; Cozaar
Intervention MeSH terms: Losartan; Amlodipine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment