A Study Examining the Effects of Nebivolol Compared to Atenolol on Endothelial Function
| Status: | Completed |
|---|---|
| Conditions: | High Blood Pressure (Hypertension) |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 3/15/2017 |
| Start Date: | May 2010 |
| End Date: | October 2016 |
A Double-blind, Placebo-controlled, Randomized Study Examining the Effects of Nebivolol Compared to Atenolol on Endothelial Function and Cardiovascular Risk in Patients With Early Vascular Disease
This is a randomized, double-blind, placebo-controlled study comparing the efficacy of
nebivolol and atenolol at improving small artery elasticity and reducing cardiovascular
disease risk in subjects with early vascular disease. Approximately 75 subjects with
borderline/elevated blood pressures and impaired endothelial function, as measured by
arterial elasticity scores, will be recruited and assigned to treatment groups using a block
randomization scheme. Patients will be randomly allocated to nebivolol, atenolol or placebo,
and then followed for 9 months.
nebivolol and atenolol at improving small artery elasticity and reducing cardiovascular
disease risk in subjects with early vascular disease. Approximately 75 subjects with
borderline/elevated blood pressures and impaired endothelial function, as measured by
arterial elasticity scores, will be recruited and assigned to treatment groups using a block
randomization scheme. Patients will be randomly allocated to nebivolol, atenolol or placebo,
and then followed for 9 months.
The Rasmussen Disease Score (RDS) test panel is the chosen methodology for this study. The
10 parameters of the RDS were selected because of their ability to quantify early structural
and functional abnormalities in the vasculature and left ventricle which appear long before
cardiovascular disease is present.
The RDS tests include: large and small artery elasticity (measured by pulse contour
analysis), resting blood pressure, mild treadmill exercise test, carotid IMT, left ventricle
mass, ECG, retinal vasculature evaluation, as well as quantification of serum NT-proBNP, and
microalbuminuria. Quantitative results from these tests are converted into categorical
classifications based on values stratified by age and gender when appropriate. The
categorical data is scored as follows: normal = 0 points, borderline = 1 point, abnormal = 2
points. Point values from all parameters are summed to create the RDS, with values ranging
from 0-20. Scores of 0-2 are classified as normal, 3-5 as early disease, and 6+ as advanced
disease. Previous research has shown that the RDS is a powerful predictor of future
cardiovascular events.
The small artery elasticity (C2) parameter is of particular interest as it is responsive to
changes in NO levels and is an effective and reliable predictor of future hypertension and
other cardiovascular events. Changes in C2 will serve as the primary outcome of this study.
Similar studies using anti-hypertensive or lipid-lowering interventions have found
significant improvements in C2 values.
Brachial artery flow-mediated dilation (FMD) measurements will also be measured as an index
of endothelial function, although this method appears to be less sensitive to functional
changes related to NO bioavailability than C2. Utilizing both FMD and C2 will allow
comparison with previous studies and take advantage of a large sample size to further
examine the relative sensitivity of each method for reliably measuring endothelial
dysfunction.
The duration of intervention for this study is 9 months which is the minimum time to
adequately detect improvement in left ventricle (LV) mass values. LV mass measurements are a
critical component of a comprehensive assessment of cardiovascular health and have improved
within this temporal window as a result of anti-hypertensive intervention.
10 parameters of the RDS were selected because of their ability to quantify early structural
and functional abnormalities in the vasculature and left ventricle which appear long before
cardiovascular disease is present.
The RDS tests include: large and small artery elasticity (measured by pulse contour
analysis), resting blood pressure, mild treadmill exercise test, carotid IMT, left ventricle
mass, ECG, retinal vasculature evaluation, as well as quantification of serum NT-proBNP, and
microalbuminuria. Quantitative results from these tests are converted into categorical
classifications based on values stratified by age and gender when appropriate. The
categorical data is scored as follows: normal = 0 points, borderline = 1 point, abnormal = 2
points. Point values from all parameters are summed to create the RDS, with values ranging
from 0-20. Scores of 0-2 are classified as normal, 3-5 as early disease, and 6+ as advanced
disease. Previous research has shown that the RDS is a powerful predictor of future
cardiovascular events.
The small artery elasticity (C2) parameter is of particular interest as it is responsive to
changes in NO levels and is an effective and reliable predictor of future hypertension and
other cardiovascular events. Changes in C2 will serve as the primary outcome of this study.
Similar studies using anti-hypertensive or lipid-lowering interventions have found
significant improvements in C2 values.
Brachial artery flow-mediated dilation (FMD) measurements will also be measured as an index
of endothelial function, although this method appears to be less sensitive to functional
changes related to NO bioavailability than C2. Utilizing both FMD and C2 will allow
comparison with previous studies and take advantage of a large sample size to further
examine the relative sensitivity of each method for reliably measuring endothelial
dysfunction.
The duration of intervention for this study is 9 months which is the minimum time to
adequately detect improvement in left ventricle (LV) mass values. LV mass measurements are a
critical component of a comprehensive assessment of cardiovascular health and have improved
within this temporal window as a result of anti-hypertensive intervention.
Inclusion Criteria:
- borderline blood pressure (120-145/80-90 mm Hg);
- borderline or abnormal small artery elasticity (C2) as measured by pulse contour
analysis;
- treatment-naive for all blood pressure medications including diuretics for at least
30 days prior to baseline visit;
- able to walk on a treadmill for 3 minutes;
- female patients with reproductive potential must use an approved contraceptive method
if appropriate (for example, intrauterine device [IUD], birth control pills, or
barrier device during and for 1 month after the last dose of study drug;
- voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.
Exclusion Criteria:
- history of intolerance to beta-blockers or clear contraindications to their use;
current pharmaceutical treatment of blood pressure;
- known history of cardiovascular disease (myocardial infarction, coronary artery
bypass graft, unstable angina, uncontrolled arrhythmias, stroke, etc.);
- known history of diabetes; known history of hepatic, renal or gastrointestinal
disorder;
- known history of any illness that may cause additional risk (as determined by study
investigator);
- pregnant or lactating women [when used during pregnancy, beta-blockers may cause
fetal harm];
- participation in a concomitant clinical trial.
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