Comparision of Blood Pressure Variability Between Amlodipine and Losartan

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.

Conditions

• Hypertension

Interventions

DRUG

Amlodipine

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.

DRUG

Losartan

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.

Sponsors & Collaborators

• Pfizer

  collaborator INDUSTRY

• Wonju Severance Christian Hospital

  lead OTHER

Principal Investigators

• Byung-Su Yoo, MD, PhD · Wonju Severance Christian Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

79 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-04-30

Primary Completion

2017-04-30

Completion

2017-05-31

Countries

• South Korea

Study Locations