Effects of Nebivolol Versus Metoprolol Succinate on Endothelial Function

Study Overview
=================
Brief Summary
-----------------
An impairment of endothelial function plays the central role in the pathogenesis of cardiovascular diseases and their complications. Most of cardiovascular risk factors are known to impair endothelial function and the established disease further aggravates endothelial dysfunction. The aim of the present study is to investigate the effects of nebivolol or metoprolol succinate on endothelial function and large artery stiffness.

Detailed Description
-----------------
The aim of this study was to compare the effects between the vasodilating β-blocker nebivolol and the cardioselective β-blocker metoprolol succinate on aortic blood pressure and left ventricular wall thickness. We conducted a randomized, double-blind study in 80 hypertensive patients. Patients received either nebivolol 5 mg or metoprolol succinate 50-100 mg daily for one year. Their heart rate, central and brachial blood pressure, mean arterial pressure, augmentation index, carotid-femoral pulse wave velocity and left ventricular wall thickness were measured at baseline and at the end of the study.

Official Title
-----------------
Comparison the Effects of Nebivolol Versus Metoprolol Succinate on Endothelial Function and Large Artery Stiffness

Conditions
-----------------
Hypertension

Intervention / Treatment
-----------------
* Drug: metoprolol succinate
* Drug: Nebivolol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with mild to moderate essential hypertension (systolic BP 140-179 mmHg and/or diastolic BP 90-109 mmHg)* Male and female patients aged 30-65 years Newly diagnosed untreated patients or previously diagnosed patients who were without treatment at least two weeks prior to screening* If patient has been taken previously antihypertensive medication the BP values are originated after untreated two weeks before randomization Exclusion Criteria: Concomitant medication: Cyclic antidepressants, MAO inhibitors, corticosteroids Diabetes I or II type (fasting venous plasma glucose > 6.4 mmol/l) Bronchial asthma and chronic obstructive airway disease Body mass index > 30 kg/m2 Ischaemic heart disease (III, IV stage, Canadian Cardiovascular Society) Clinically relevant heart failure (NYHA class II - IV) Clinically relevant valve disease (physical examination) Arrhythmias and conduction disturbances, requiring therapy, sinus bradycardia at rest < 50 b/min, sick sinus syndrome, AV - block stage II - III Secondary hypertension (urea >8.3 mmol/l, creatinine >120μmol/l (males), >103 μmol/l (females), TSH > 4.0mIU/l, free T4 > 27 pmol/l) Clinically relevant atherosclerotic disease of lower extremities Acute inflammation (according to CRP > 10mg/l) Hypercholesterolemia (> 6,5 mmol/l) Allergic reaction to beta-blockers Pregnant or breast-feeding women History of hepatic, renal, metabolic or endocrine diseases Smoking > 10 cigarettes per day Alcohol consumption > 7 drinks per week (drink = 0,33 l beer, 120 ml wine or 30 ml strong alcoholic drink) The patient has had surgery or disease of the gastrointestinal tract which, in the opinion of the investigator, may influence the absorption or elimination of the study drug. The patient has a severe organic disorder that may interfere with the absorption, pharmacokinetics, or elimination of the study medication. The patient has a comorbid condition that would be expected to result in death during the trial period (e.g., terminal cancer, AIDS). The patient has chronic psychoses or behavioural conditions that would limit the ability of the patient to comply with the requirements of this study. The patient has known hypersensitivity to Nebivolol, Metoprolol or hydrochlorothiazide related compounds. Patient is enrolled in another clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: metoprolol, tablets<br>metoprolol succinate 50-100 mg orally daily for one year | Drug: metoprolol succinate<br>* once daily 50 or 100 mg for one year<br>* Other names: Corvitol;|
| Experimental: nebivolol<br>nebivolol 5 mg capsule once daily for one year | Drug: Nebivolol<br>* once daily 5 mg capsule for one year<br>* Other names: Nebilet;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of nebivolol and metoprolol on endothelial function | High-fidelity micromanometer (applanation tonometry) from both wrists and PWA, which is to be performed of the systolic portion (SphygmoCor Px, version 7.0) of the pulse curve. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in carotid artery intima-media thickness | Ultrasound scanner,with an 12 MHz transducer. Longitudinal images from 3 projections (anterolateral, lateral, and posterolateral) are measured for the common carotid artery, carotid bulb, and internal carotid artery | 12 months | 
| Change in left ventricular mass index, systolic and diastolic function | 2-dimensional echocardiography using the standard apical 4-chamber view | 12 months | 
| Arterial Compliance | Peripheral blood pressure and arterial waveform to be measured in the dominant arm by a Cardiovascular Profiling Instrument | 12 months |