Comparison of Effect of cARvedilol Compared To bISoprolol on cenTral Pulse Pressure in Hypertension (ARTIST) Study

Study Overview
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Brief Summary
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The purpose of this study is to compare of carvedilol, a vasodilating beta-blocker and bisoprolol, a beta1- selective beta-blocker for reducing the central pulse pressure and thereby left ventricular (LV) mass in never-treated hypertensive patients.

Detailed Description
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Carvedilol and bisoprolol are established beta-blockers for treating hypertension or chronic heart failure because these beta-blockers have cardio-protective effects. Recent studies have shown that the change in central pulse pressure is more closely associated with the change in cardiac load than the change in brachial pressure during hypertension treatment. Vasodilating beta-blockers may decrease central pulse pressure more than beta1- selective beta-blockers, because vasodilators reduced the magnitude of reflection wave by dilating peripheral muscular arteries. The investigators hypothesized that carvedilol, a vasodilating beta-blocker, would be more effective than bisoprolol, a beta1- selective beta-blocker in reducing central pulse pressure and thereby LV mass, through the reduction in the magnitude of reflection wave. The aim of the present study was to test this hypothesis in an active controlled, 2-arm parallel group comparison, prospective randomized open blinded end-point (PROBE) design study. At least 100 patients will be enrolled in each group and the follow up duration will be 48 weeks. The primary endpoint is to compare the change in central pulse pressure between the two groups.

Official Title
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Comparison of Effect of cARvedilol Compared To bISoprolol on cenTral Pulse Pressure in Hypertension (ARTIST) Study

Conditions
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Hypertension

Intervention / Treatment
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* Drug: carvedilol
* Drug: bisoprolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Never-treated hypertensive subjects, aged 20-80 years (at the time of informed consent), regardless of sex Clinic systolic BP/diastolic BP > 140/90 mmHg in a sitting position. Exclusion Criteria: Beta-blocker contraindications(asthma, COPD…) Heart rate less than 55 bpm Subjects treated with nitrates Grade 3 hypertension (≥180 and/or ≥110 mmHg) Secondary hypertension or malignant hypertension History of heart failure, coronary artery disease, and stroke Arrhythmia Renal dysfunction (serum creatinine ≥2.0 mg/dl) Hepatic dysfunction (AST and/or ALT ≥100 IU/l) A history of or a suspected malignant tumor within 5 years of enrollment Chronic inflammatory disease Pregnancy, childbearing potential with inadequate contraception, breast feeding Inability to give informed consent

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: carvedilol<br>carvedilol is administered after randomization at a dose of 10 mg once daily, and if needed, titrated to 15 mg and to a maximum of 20 mg to achieve a clinic BP <140/90 mmHg. | Drug: carvedilol<br>* carvedilol is administered after randomization at a dose of 10 mg once daily, and if needed, titrated to 15 mg and to a maximum of 20 mg to achieve a clinic BP <140/90 mmHg.<br>|
| Experimental: bisoprolol<br>bisoprolol is administered after randomization at a dose of 2.5 mg once daily, and if needed, titrated to 3.75 mg and to a maximum of 5.0 mg to achieve a clinic BP <140/90 mmHg. | Drug: bisoprolol<br>* bisoprolol is administered after randomization at a dose of 2.5 mg once daily, and if needed, titrated to 3.75 mg and to a maximum of 5.0 mg to achieve a clinic BP <140/90 mmHg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in central pulse pressure (pulse pressure amplification) |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LV mass index Changes in LV diastolic functions (E/Em, left atrium volume) Changes in urinary albumin excretion, B-type natriuretic peptide (BNP), HOMA-IR, and oxidative stress (urinary 8-isoprostane). Change in ambulatory BP |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, carvedilol, bisoprolol, central pulse pressure, pulse pressure amplification, reflection magnitude, LV mass index, LV diastolic function