Page last updated: 2024-12-06

nebivolol

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Nebivolol is a selective beta1-adrenergic receptor blocker used primarily to treat hypertension. It has a unique pharmacological profile that combines beta-blockade with vasodilatory effects due to its ability to stimulate nitric oxide release. Nebivolol is synthesized through a multi-step process involving chiral resolution and amide coupling. It is typically administered orally and is well-absorbed with a bioavailability of approximately 80%. Nebivolol is studied extensively for its potential to improve cardiovascular outcomes, including reducing the risk of stroke, heart failure, and mortality in patients with hypertension and coronary artery disease. The compound's unique vasodilatory properties make it particularly attractive for patients with endothelial dysfunction and peripheral vascular disease. Nebivolol is also being investigated for its potential neuroprotective effects, as it has shown promising results in preclinical studies for the treatment of Alzheimer's disease and other neurodegenerative disorders.'

2,2'-iminobis[1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanol] : A member of the class of chromanes that is 2,2'-iminodiethanol in which one hydrogen attached to each hydroxy-bearing carbon is replaced by a 6-fluorochroman-2-yl group. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID71301
CHEMBL ID434394
CHEBI ID64019
CHEBI ID64022
SCHEMBL ID19863
MeSH IDM0149652

Synonyms (65)

Synonym
AC-1611
PDSP2_000243
2h-1-benzopyran-2-methanol, alpha,alpha'-(iminobis(methylene))bis(6-fluoro-3,4-dihydro-
nebivololum [latin]
alpha,alpha'-(iminobis(methylene))bis(6-fluoro-3,4-dihydro)-2h-1-benzopyran-2-methanol
alpha,alpha'-(iminodimethylene)bis(6-fluoro-2-chromanmethanol)
PDSP1_000244
99200-09-6
2,2'-iminobis[1-(6-fluoro-3,4-dihydro-2h-chromen-2-yl)ethanol]
chebi:64019 ,
CHEMBL434394
narbivolol
DB04861
L001284
1-(6-fluoro-3,4-dihydro-2h-chromen-2-yl)-2-[[2-(6-fluoro-3,4-dihydro-2h-chromen-2-yl)-2-hydroxyethyl]amino]ethanol
A845981
nsc_71301
bdbm84735
cas_99200-09-6
FT-0672664
FT-0672663
FT-0672666
FT-0631000
1,1'-bis(6-fluoro-3,4-dihydro-2h-1-benzopyran-2-yl)-2,2'-iminodiethanol
alpha,alpha'-(iminobismethylene)bis-(6-fluoro-3,4-dihydro-2h-1-benzopyran-2-methanol)
1,1'-[bis(6-fluoro-3,4-dihydro-2h-1-benzopyran-2-yl)]-2,2'-iminodiethanol
alpha,alpha'-(iminodimethylene)bis-(6-fluoro-2-chromanmethanol)
AKOS015895102
1-(6-fluoro-3,4-dihydro-2h-1-benzopyran-2-yl)-2-{[2-(6-fluoro-3,4-dihydro-2h-1-benzopyran-2-yl)-2-hydroxyethyl]amino}ethan-1-ol
gtpl7246
ro-67555
SCHEMBL19863
alpha,alpha'[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2h-1-benzopyran-2-methanol]
alpha,alpha'-[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2h-1-benzopyran-2-methanol]
KOHIRBRYDXPAMZ-UHFFFAOYSA-N
HMS3604L09
(-)-nebivolol; levonebivolol; l-nebivolol
9920-09-6
DTXSID9040556 ,
nebivololum
SR-01000883933-1
sr-01000883933
mfcd00865796
1-(6-fluorochroman-2-yl)-2-[[2-(6-fluorochroman-2-yl)-2-hydroxyethyl]amino]ethanol
2,2'-azanediylbis(1-(6-fluorochroman-2-yl)ethanol)
FT-0700072
Q418130
FT-0672665
CCG-357228
see n387903
AS-77015
EN300-7392989
r 74714
(alphar,alpha'r,2r,2's)-alpha,alpha'-[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2h-1-benzopyran-2-methanol]
CS-0143939
(rac)-nebivolol
HY-B0203B
nebivolol (mart.)
c07ab12
nebibolol
chebi:64022
(1rs,1'rs)-2,2'-iminobis(1-((2rs,2'sr)-6-fluoro-3,4-dihydro-2h-chromen-2-yl)ethanol)
byvalson component of nebivolol
dtxcid7020556
(1rs,1'rs)-1,1'-((2rs,2'sr)-bis(6-fluorochroman-2-yl))-2,2'-iminodiethanol

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" A comparison is also presented between several methods based on animal pharmacokinetic data, using the same set of proprietary compounds, and it lends further support for the use of this method, as opposed to methods that require the gathering of pharmacokinetic data in laboratory animals."( Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
Gao, F; Lombardo, F; Obach, RS; Shalaeva, MY, 2004
)
0.32
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (5)

ClassDescription
organofluorine compoundAn organofluorine compound is a compound containing at least one carbon-fluorine bond.
secondary amino compoundA compound formally derived from ammonia by replacing two hydrogen atoms by organyl groups.
secondary alcoholA secondary alcohol is a compound in which a hydroxy group, -OH, is attached to a saturated carbon atom which has two other carbon atoms attached to it.
diolA compound that contains two hydroxy groups, generally assumed to be, but not necessarily, alcoholic. Aliphatic diols are also called glycols.
chromanes
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (1)

PathwayProteinsCompounds
Nebivolol Action Pathway478

Protein Targets (6)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Potassium voltage-gated channel subfamily E member 1Homo sapiens (human)IC50 (µMol)27.82980.12004.048010.0000AID1207377; AID1207407
Potassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)IC50 (µMol)27.82980.12004.048010.0000AID1207377; AID1207407
Potassium voltage-gated channel subfamily H member 2Homo sapiens (human)IC50 (µMol)4.31180.00091.901410.0000AID1207471; AID1207501; AID1207531
Voltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)IC50 (µMol)15.84890.00032.25459.6000AID1207287
Sodium channel protein type 5 subunit alphaHomo sapiens (human)IC50 (µMol)7.12640.00033.64849.2000AID1207317; AID1207347
Potassium voltage-gated channel subfamily D member 3Homo sapiens (human)IC50 (µMol)50.11871.40005.35009.3000AID1207437
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (112)

Processvia Protein(s)Taxonomy
epithelial cell maturationPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
sensory perception of soundPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
male gonad developmentPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
vestibular nucleus developmentPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
secretory granule organizationPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
regulation of ventricular cardiac muscle cell membrane repolarizationPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
cellular response to cAMPPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
cellular response to acidic pHPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
cellular response to light stimulusPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
potassium ion transmembrane transportPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
cardiac muscle cell action potential involved in contractionPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
cardiac muscle cell contractionPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
membrane repolarizationPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
membrane repolarization during action potentialPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
membrane repolarization during cardiac muscle cell action potentialPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
negative regulation of protein targeting to membranePotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
potassium ion export across plasma membranePotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
membrane repolarization during ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
positive regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
regulation of delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
negative regulation of delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
gastrin-induced gastric acid secretionPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
glucose metabolic processPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
heart developmentPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
sensory perception of soundPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
rhythmic behaviorPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
regulation of heart contractionPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
regulation of blood pressurePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
positive regulation of heart ratePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
iodide transportPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
erythrocyte differentiationPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
intracellular chloride ion homeostasisPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
response to insulinPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
social behaviorPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
corticosterone secretionPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
inner ear morphogenesisPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
inner ear developmentPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
intestinal absorptionPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
detection of mechanical stimulus involved in sensory perception of soundPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
potassium ion homeostasisPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
cardiac muscle contractionPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
auditory receptor cell developmentPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
regulation of membrane repolarizationPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
regulation of ventricular cardiac muscle cell membrane repolarizationPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
regulation of atrial cardiac muscle cell membrane repolarizationPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
positive regulation of cardiac muscle contractionPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
regulation of gastric acid secretionPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
stomach developmentPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
renal absorptionPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
renal sodium ion absorptionPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
cellular response to cAMPPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
cellular response to xenobiotic stimulusPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
potassium ion transmembrane transportPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
cellular response to epinephrine stimulusPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
adrenergic receptor signaling pathwayPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
cardiac muscle cell contractionPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
membrane repolarization during action potentialPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
membrane repolarization during cardiac muscle cell action potentialPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
atrial cardiac muscle cell action potentialPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
cochlea developmentPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
potassium ion export across plasma membranePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
membrane repolarization during atrial cardiac muscle cell action potentialPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
membrane repolarization during ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
positive regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
non-motile cilium assemblyPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
potassium ion import across plasma membranePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
action potentialPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by hormonePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of DNA-templated transcriptionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion homeostasisPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cardiac muscle contractionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of ventricular cardiac muscle cell membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cellular response to xenobiotic stimulusPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane depolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion import across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
immune system developmentVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
positive regulation of cytosolic calcium ion concentrationVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
heart developmentVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ionVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
embryonic forelimb morphogenesisVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
camera-type eye developmentVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
positive regulation of adenylate cyclase activityVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
positive regulation of muscle contractionVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
calcium ion transport into cytosolVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
cardiac conductionVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
calcium ion transmembrane transport via high voltage-gated calcium channelVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
calcium ion transmembrane transportVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
cardiac muscle cell action potential involved in contractionVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
membrane depolarization during cardiac muscle cell action potentialVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
membrane depolarization during AV node cell action potentialVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
cell communication by electrical coupling involved in cardiac conductionVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
regulation of heart rate by cardiac conductionVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
regulation of ventricular cardiac muscle cell action potentialVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
membrane depolarization during atrial cardiac muscle cell action potentialVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
calcium ion import across plasma membraneVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
regulation of heart rateSodium channel protein type 5 subunit alphaHomo sapiens (human)
cardiac conduction system developmentSodium channel protein type 5 subunit alphaHomo sapiens (human)
cardiac ventricle developmentSodium channel protein type 5 subunit alphaHomo sapiens (human)
brainstem developmentSodium channel protein type 5 subunit alphaHomo sapiens (human)
sodium ion transportSodium channel protein type 5 subunit alphaHomo sapiens (human)
positive regulation of sodium ion transportSodium channel protein type 5 subunit alphaHomo sapiens (human)
response to denervation involved in regulation of muscle adaptationSodium channel protein type 5 subunit alphaHomo sapiens (human)
telencephalon developmentSodium channel protein type 5 subunit alphaHomo sapiens (human)
cerebellum developmentSodium channel protein type 5 subunit alphaHomo sapiens (human)
sodium ion transmembrane transportSodium channel protein type 5 subunit alphaHomo sapiens (human)
odontogenesis of dentin-containing toothSodium channel protein type 5 subunit alphaHomo sapiens (human)
positive regulation of action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
positive regulation of epithelial cell proliferationSodium channel protein type 5 subunit alphaHomo sapiens (human)
membrane depolarizationSodium channel protein type 5 subunit alphaHomo sapiens (human)
cardiac muscle contractionSodium channel protein type 5 subunit alphaHomo sapiens (human)
regulation of ventricular cardiac muscle cell membrane repolarizationSodium channel protein type 5 subunit alphaHomo sapiens (human)
regulation of atrial cardiac muscle cell membrane depolarizationSodium channel protein type 5 subunit alphaHomo sapiens (human)
regulation of atrial cardiac muscle cell membrane repolarizationSodium channel protein type 5 subunit alphaHomo sapiens (human)
regulation of ventricular cardiac muscle cell membrane depolarizationSodium channel protein type 5 subunit alphaHomo sapiens (human)
cellular response to calcium ionSodium channel protein type 5 subunit alphaHomo sapiens (human)
cardiac muscle cell action potential involved in contractionSodium channel protein type 5 subunit alphaHomo sapiens (human)
regulation of cardiac muscle cell contractionSodium channel protein type 5 subunit alphaHomo sapiens (human)
ventricular cardiac muscle cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
membrane depolarization during action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
membrane depolarization during cardiac muscle cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
atrial cardiac muscle cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
SA node cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
AV node cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
bundle of His cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
membrane depolarization during AV node cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
membrane depolarization during SA node cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
membrane depolarization during Purkinje myocyte cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
membrane depolarization during bundle of His cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
AV node cell to bundle of His cell communicationSodium channel protein type 5 subunit alphaHomo sapiens (human)
regulation of heart rate by cardiac conductionSodium channel protein type 5 subunit alphaHomo sapiens (human)
membrane depolarization during atrial cardiac muscle cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
regulation of sodium ion transmembrane transportSodium channel protein type 5 subunit alphaHomo sapiens (human)
potassium ion transportPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
protein homooligomerizationPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
membrane repolarizationPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
membrane repolarization during cardiac muscle cell action potentialPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
potassium ion export across plasma membranePotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
membrane repolarization during ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
ventricular cardiac muscle cell membrane repolarizationPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
action potentialPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (42)

Processvia Protein(s)Taxonomy
voltage-gated potassium channel activityPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
protein bindingPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
potassium channel regulator activityPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
telethonin bindingPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
protein-containing complex bindingPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
transmembrane transporter bindingPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
voltage-gated potassium channel activityPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
voltage-gated potassium channel activityPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
protein bindingPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
calmodulin bindingPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
phosphatidylinositol-4,5-bisphosphate bindingPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
protein phosphatase 1 bindingPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
outward rectifier potassium channel activityPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
protein kinase A catalytic subunit bindingPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
protein kinase A regulatory subunit bindingPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
transmembrane transporter bindingPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
voltage-gated potassium channel activity involved in atrial cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
scaffold protein bindingPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
transcription cis-regulatory region bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ubiquitin protein ligase bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
identical protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein homodimerization activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
C3HC4-type RING finger domain bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
scaffold protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
high voltage-gated calcium channel activityVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
voltage-gated calcium channel activity involved in cardiac muscle cell action potentialVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
voltage-gated calcium channel activityVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
protein bindingVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
calmodulin bindingVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
high voltage-gated calcium channel activityVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
metal ion bindingVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
alpha-actinin bindingVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
voltage-gated calcium channel activity involved in cardiac muscle cell action potentialVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
voltage-gated calcium channel activity involved in AV node cell action potentialVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
voltage-gated sodium channel activitySodium channel protein type 5 subunit alphaHomo sapiens (human)
protein bindingSodium channel protein type 5 subunit alphaHomo sapiens (human)
calmodulin bindingSodium channel protein type 5 subunit alphaHomo sapiens (human)
fibroblast growth factor bindingSodium channel protein type 5 subunit alphaHomo sapiens (human)
enzyme bindingSodium channel protein type 5 subunit alphaHomo sapiens (human)
protein kinase bindingSodium channel protein type 5 subunit alphaHomo sapiens (human)
protein domain specific bindingSodium channel protein type 5 subunit alphaHomo sapiens (human)
ankyrin bindingSodium channel protein type 5 subunit alphaHomo sapiens (human)
ubiquitin protein ligase bindingSodium channel protein type 5 subunit alphaHomo sapiens (human)
transmembrane transporter bindingSodium channel protein type 5 subunit alphaHomo sapiens (human)
nitric-oxide synthase bindingSodium channel protein type 5 subunit alphaHomo sapiens (human)
voltage-gated sodium channel activity involved in cardiac muscle cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
voltage-gated sodium channel activity involved in AV node cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
voltage-gated sodium channel activity involved in bundle of His cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
voltage-gated sodium channel activity involved in Purkinje myocyte action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
voltage-gated sodium channel activity involved in SA node cell action potentialSodium channel protein type 5 subunit alphaHomo sapiens (human)
scaffold protein bindingSodium channel protein type 5 subunit alphaHomo sapiens (human)
A-type (transient outward) potassium channel activityPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
protein bindingPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
transmembrane transporter bindingPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
metal ion bindingPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
voltage-gated potassium channel activityPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (41)

Processvia Protein(s)Taxonomy
voltage-gated potassium channel complexPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
lysosomePotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
cell surfacePotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
apical plasma membranePotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
Z discPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
membrane raftPotassium voltage-gated channel subfamily E member 1Homo sapiens (human)
early endosomePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
endoplasmic reticulumPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
cytoplasmPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
lysosomePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
early endosomePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
late endosomePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
endoplasmic reticulumPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
voltage-gated potassium channel complexPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
membranePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
basolateral plasma membranePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
apical plasma membranePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
transport vesiclePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
cytoplasmic vesicle membranePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
neuron projectionPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
neuronal cell bodyPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
membrane raftPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
ciliary basePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
lumenal side of membranePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
basolateral part of cellPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
monoatomic ion channel complexPotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
membranePotassium voltage-gated channel subfamily KQT member 1Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cell surfacePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
perinuclear region of cytoplasmPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cytoplasmVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
plasma membraneVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
postsynaptic densityVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
membraneVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
Z discVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
dendriteVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
perikaryonVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
postsynaptic density membraneVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
L-type voltage-gated calcium channel complexVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
voltage-gated calcium channel complexVoltage-dependent L-type calcium channel subunit alpha-1CHomo sapiens (human)
caveolaSodium channel protein type 5 subunit alphaHomo sapiens (human)
nucleoplasmSodium channel protein type 5 subunit alphaHomo sapiens (human)
nucleolusSodium channel protein type 5 subunit alphaHomo sapiens (human)
endoplasmic reticulumSodium channel protein type 5 subunit alphaHomo sapiens (human)
plasma membraneSodium channel protein type 5 subunit alphaHomo sapiens (human)
caveolaSodium channel protein type 5 subunit alphaHomo sapiens (human)
cell surfaceSodium channel protein type 5 subunit alphaHomo sapiens (human)
intercalated discSodium channel protein type 5 subunit alphaHomo sapiens (human)
membraneSodium channel protein type 5 subunit alphaHomo sapiens (human)
lateral plasma membraneSodium channel protein type 5 subunit alphaHomo sapiens (human)
Z discSodium channel protein type 5 subunit alphaHomo sapiens (human)
T-tubuleSodium channel protein type 5 subunit alphaHomo sapiens (human)
sarcolemmaSodium channel protein type 5 subunit alphaHomo sapiens (human)
perinuclear region of cytoplasmSodium channel protein type 5 subunit alphaHomo sapiens (human)
voltage-gated sodium channel complexSodium channel protein type 5 subunit alphaHomo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
sarcolemmaPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
GABA-ergic synapsePotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
postsynaptic specialization membranePotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
voltage-gated potassium channel complexPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
dendritic spinePotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
neuronal cell bodyPotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
postsynaptic membranePotassium voltage-gated channel subfamily D member 3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (34)

Assay IDTitleYearJournalArticle
AID26362Ionization constant (pKa)2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1207501Inhibition of rapid delayed inward rectifying potassium current (IKr) in Chinese hamster ovary (CHO) cells stable expressing hERG measured using IonWorks Barracuda automated patch clamp platform
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1207531Inhibition of rapid delayed inward rectifying potassium current (IKr) measured using manual patch clamp assay
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1207377Inhibition of slow delayed inward rectifying potassium current (Iks) in Chinese Hamster Ovary (CHO) cells expressing hKvLQT1/hminK measured using IonWorks Quattro automated patch clamp platform
AID8002Observed volume of distribution2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
AID1207347Inhibition of fast sodium current (INa) in HEK293 cells transfected with human Nav1.5 measured using IonWorks Quattro automated patch clamp platform
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1207317Inhibition of fast sodium current (INa) in Chinese Hamster Ovary (CHO) K1 cells transfected with human Nav1.5 measured using IonWorks Quattro automated patch clamp platform
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1207437Inhibition of transient outward potassium current (Ito) current in Chinese Hamster Ovary (CHO) K1 cells expressing human Kv4.3 measured using IonWorks Quattro automated patch clamp platform
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1207565Inhibition of long-lasting type calcium current (hICa) in Chinese Hamster Ovary (CHO) cells expressing hCav1.2 measured using IonWorks Quattro automated patch clamp platform
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID781328pKa (acid-base dissociation constant) as determined by Luan ref: Pharm. Res. 20052014Pharmaceutical research, Apr, Volume: 31, Issue:4
Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds.
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1207471Inhibition of rapid delayed inward rectifying potassium current (IKr) in Chinese hamster ovary (CHO) K1 cells stably expressing hERG measured using IonWorks Quattro automated patch clamp platform
AID7783Unbound fraction (plasma)2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1207407Inhibition of slow delayed inward rectifying potassium current (Iks) in Chinese Hamster Ovary (CHO) cells transfected with KCNQ1 / Kv1.7 / KvLQT1 and KCNE1/minK measured using IonWorks automated patch clamp platform
AID1207287Inhibition of long-lasting type calcium current (ICaL) in HEK293 cells (alpha1C/beta2a/alpha2delta1) cells measured using IonWorks Barracuda automated patch clamp platform
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (5)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's2 (40.00)29.6817
2010's3 (60.00)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 117.91

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index117.91 (24.57)
Research Supply Index1.95 (2.92)
Research Growth Index4.63 (4.65)
Search Engine Demand Index209.54 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (117.91)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews1 (16.67%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other5 (83.33%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (102)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Danish Trial of Beta Blocker Treatment After Myocardial Infarction Without Reduced Ejection Fraction (DANBLOCK) [NCT03778554]Phase 42,760 participants (Anticipated)Interventional2018-12-17Recruiting
N-of-1 Trials for Deprescribing Beta-blockers in HFpEF [NCT04767061]Phase 49 participants (Actual)Interventional2021-04-01Completed
Regression of Myocardial Steatosis by Nebivolol [NCT01358409]Early Phase 131 participants (Actual)Interventional2011-04-01Completed
Olmesartan Versus Nebivolol in Management of Hypertension in Acute Ischemic Stroke [NCT03655964]Phase 260 participants (Actual)Interventional2018-08-20Completed
A Prospective, Randomized, Open-Label, Active-Comparator, Blinded-Endpoint, 12-week Forced-Titration Study of the Efficacy and Safety of Nebivolol Verses Metoprolol in Hypertensive Subjects Taking Amlodipine [NCT03635125]Phase 440 participants (Actual)Interventional2010-08-30Completed
An Open-label, Randomized Study Evaluating the Long-term Effects of Metoprolol (MET) Versus Nebivolol (NEB) as Monotherapy or in Combination With Amlodipine or Hydrochlorothiazide for the Treatment of Patients With Hypertension [NCT00142584]Phase 3336 participants (Actual)Interventional2005-08-31Completed
Use of Determination of Drug Levels to Optimize Pharmacotherapy of Heart Failure [NCT06035978]Phase 4100 participants (Anticipated)Interventional2023-11-30Not yet recruiting
Dose Response and Receptor Selectivity of Beta-blocker Effects on Bone Metabolism [NCT02467400]Early Phase 1165 participants (Actual)Interventional2015-07-01Completed
The Impact of Heart Rate on Central Hemodynamics in Sick Sinus Syndrome Patients With a Permanent Cardiac Pacemaker [NCT03245996]Phase 427 participants (Actual)Interventional2015-06-30Completed
Comparative Study of the Effects of Telmisartan and Nebivolol on 24-h Ambulatory Blood Pressure and Arterial Stiffness in Patients With Arterial Hypertension [NCT02057328]Phase 480 participants (Anticipated)Interventional2010-12-31Recruiting
Open-label, Multicenter, Multinational, Interventional Clinical Trial to Assess Effectiveness and SAfety of the Extemporaneous Combination of Nebivolol and Zofenopril Calcium in Grade 1 to 2 Hypertensive patIents Versus Each mOnotherapy [NCT05257148]Phase 4296 participants (Actual)Interventional2021-04-28Completed
Efficacy of Medical Therapy in Women and Men With Angina and Myocardial Bridging [NCT04130438]Phase 2360 participants (Anticipated)Interventional2020-10-15Suspended(stopped due to Low enrollment, modifying study protocol)
An Open Label, Randomized, 2-Period, 2- Treatment, 2 -Sequence, Crossover, Single-Dose BE Study of Nebivolol 20 mg Tablet [Torrent, India]Versus Bystolic® 20 mg Tablet [ Forest Pharmaceuticals Inc., USA] in Healthy Subjects - Fasted. [NCT03517020]Phase 122 participants (Actual)Interventional2011-04-30Completed
A Multicenter, Randomized, Double-blind, Placebo-Controlled, 8-Week Study to Evaluate the Safety and Efficacy of Nebivolol and Valsartan Given as a Fixed Dose Combination in Patients With Stage 1 or 2 Essential Hypertension [NCT01508026]Phase 34,161 participants (Actual)Interventional2012-01-31Completed
The Effect of Nebivolol in Hypertensive Patients With Coronary Arterial Spasm [NCT03930433]Phase 451 participants (Actual)Interventional2018-01-01Completed
Managing Endothelial Dysfunction in COVID-19 : A Randomized Controlled Trial at the Lebanese American University Medical Center- Rizk Hospital [NCT04631536]Phase 342 participants (Actual)Interventional2021-01-10Active, not recruiting
Effects of Nebivolol on Exercise Tolerance and Left Ventricular Systolic and Diastolic Function [NCT01056718]53 participants (Actual)Interventional2009-11-30Completed
Effects of the Novel Beta-adrenergic Antagonist Nebivolol (Bystolic) on Prehypertensive Subjects at Genetic Risk of Hypertension: Implications for Inflammation, Endothelial Dysfunction, and Oxidative Stress. [NCT01202175]Phase 450 participants (Actual)Interventional2010-07-31Completed
Effect of Nebivolol on Forearm Vasodilation, Nitric Oxide Bioavailability, and Oxidative Stress in Patients With Stage 1/2 Hypertension [NCT00648895]Phase 312 participants (Actual)Interventional2007-11-30Completed
A Blinded Crossover Study of the 24 Hour Blood Pressure Response to Treatment of Obstructive Sleep Apnea Associated Hypertension With Nebivolol or Hydrochlorothiazide [NCT02710071]Phase 441 participants (Actual)Interventional2015-01-31Completed
A Trial to Compare the Effects of Nebivolol Versus Atenolol on Various Cardiovascular Measurements Including Insulin Sensitivity [NCT00125853]54 participants (Actual)Interventional2006-07-31Completed
Association Between Angiotensin Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use and COVID-19 Severity and Mortality Among US Veterans [NCT04467931]22,213 participants (Actual)Observational2020-01-19Completed
Nebivolol in Chronic Obstructive Pulmonary Disease [NCT01939990]Phase 2/Phase 30 participants (Actual)Interventional2012-01-31Withdrawn(stopped due to Funding was discontinued.)
Effects of NEbivolol on Subclinical Left Ventricular dYSfunction. A Comparative Study Against Metoprolol. The ENESYS Study. A Phase 3, Randomised, Parallel, Active-controlled, Open Label Study [NCT00942487]Phase 360 participants (Actual)Interventional2005-04-30Completed
Glycemic Effects of Nebivolol Compared With Metoprolol Extended Release and Compared With Hydrochlorothiazide In Hypertensive Patients With Type 2 Diabetes Mellitus: A Pilot Study [NCT00744237]Phase 4231 participants (Actual)Interventional2008-08-31Completed
Echocardiographic Study of a Single Dose Bisoprolol Versus Nebivolol in Healthy Subjects: a Randomized, Double-blind, Cross-over Study [NCT04432610]Phase 40 participants (Actual)Interventional2030-01-31Withdrawn(stopped due to COVID pandemic)
Effects of Losartan vs. Nebivolol vs. the Association of Both on the Progression of Aortic Root Dilation in Marfan Syndrome (MFS) With FBN1 Gene Mutations. [NCT00683124]Phase 3291 participants (Anticipated)Interventional2008-07-31Recruiting
A 25 Week, Open Label Study to Determine the Effects of Nebivolol When Added to Hydrochlorothiazide on Diastolic Function and Arterial Stiffness in African Americans With Hypertension [NCT00999752]40 participants (Actual)Interventional2009-10-31Completed
Impact of Nebivolol on Central Aortic Pressure [NCT01051947]0 participants (Actual)Interventional2009-12-31Withdrawn(stopped due to Similar study already published)
The Effects of Nebivolol on Aortic Impedance Parameters in Type 2 Diabetics [NCT00829296]Phase 2/Phase 370 participants (Actual)Interventional2009-01-31Completed
A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of Nebivolol Added To Antihypertensive Treatment With Lisinopril or Losartan in Patients With Hypertension. [NCT00734630]Phase 4491 participants (Actual)Interventional2008-08-31Completed
Cardioprotective Effects of Nebivolol Versus Placebo in Patients Undergoing Chemotherapy With Anthracyclines (CONTROL Trial) [NCT05728632]Phase 380 participants (Actual)Interventional2019-01-01Active, not recruiting
NT-proBNP Selected PreventiOn of Cardiac eveNts in a populaTion of dIabetic Patients Without A History of Cardiac Disease: a Prospective Randomized Trial [NCT02817360]Phase 42,400 participants (Anticipated)Interventional2016-02-29Recruiting
Tolerability of Nebivolol Compared With Metoprolol ER in Patients With Mild to Moderate Hypertension Taking Hydrochlorothiazide (HCTZ) [NCT00547300]Phase 349 participants (Actual)Interventional2007-10-31Terminated
An Open Label, Multi-centre, Non-interventional Post-marketing Surveillance (PMS) to Monitor the Safety and Effectiveness of Nebilet Administered in Korean Patients According to the Prescribing Information [NCT01077661]743 participants (Actual)Observational2009-10-31Completed
Comparative Effects of Nebivolol and Carvedilol on Diastolic Function of the Left Ventricle in the Elderly Heart Failure Patients With Preserved Ejection Fraction: Study Protocol for a Randomized Controlled Trial [NCT02619526]62 participants (Anticipated)Interventional2016-12-31Recruiting
Blood Pressure and Metabolic Effects of Nebivolol Compared With Hydrochlorothiazide and Placebo in Hypertensive Patients With Impaired Glucose Tolerance or Impaired Fasting Glucose [NCT00673790]Phase 4537 participants (Actual)Interventional2008-05-15Completed
A Randomized, Double-blind, Parallel-Group Study to Evaluate the Effects of First-Line Treatment With a Free Combination of Nebivolol and Lisinopril Compared With Placebo and the Monotherapy Components on Blood Pressure in Patients With Stage 2 Diastolic [NCT01218100]Phase 4664 participants (Actual)Interventional2010-10-31Completed
A Prospective, Randomized, Double-Blind, Placebo Controlled Study of the Long-Term Efficacy of Nebivolol in Hypertensive Patients After Withdrawal of Therapy [NCT00785512]Phase 4207 participants (Actual)Interventional2008-11-30Completed
N-of-1 Trials for Deprescribing Beta-blockers in HFpEF [NCT04757584]Phase 49 participants (Actual)Interventional2021-04-01Completed
A Randomized, Parallel Group Safety Evaluation of Electrocardiographic Intervals and Blood Pressure in Normal Healthy Volunteers After Nebivolol, Atenolol, Moxifloxacin, or Placebo Administration After Single and Repeated Doses [NCT00158093]Phase 1260 participants Interventional2003-06-30Completed
Comparative Blood Pressure Effects of Nebivolol Versus Lisinopril in Patients With New Onset or Exacerbated Hypertension Induced by Bevacizumab: a Crossover Study [NCT01076140]0 participants (Actual)Interventional2010-02-28Withdrawn(stopped due to No participants enrolled)
Nebivolol Effects on Endothelial Function and Erectile Function in Non-smoking Pre-hypertensive and Newly Diagnosed Stage 1 Hypertensive Men With Erectile Dysfunction. [NCT01885988]Phase 470 participants (Anticipated)Interventional2013-03-31Recruiting
The Usefulness of Non-invasive Assessment of Haemodynamic Profile in the Diagnosis and Treatment of Hypertension [NCT01996085]144 participants (Actual)Interventional2013-01-31Completed
A Double-Blind, Multi-Center, Randomized, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Nebivolol Added to Existing Antihypertensive Treatment in Patients With Mild to Moderate Hypertension [NCT00200434]Phase 3600 participants Interventional2002-10-31Completed
A Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Examine the Effect of Nebivolol, a Beta-Blockade Drug, for the Prevention of Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy [NCT01648634]Phase 351 participants (Actual)Interventional2012-02-13Completed
Collaborative Systematic Overview of Randomised Controlled Trials of Beta-Blockers in the Treatment of Heart Failure [NCT00832442]18,240 participants (Anticipated)Observational2008-08-31Enrolling by invitation
Nebivolol Effect on Nitric Oxide Levels, Blood Pressure, and Renal Function in Kidney Transplant Patients [NCT01157234]Phase 432 participants (Actual)Interventional2010-07-31Completed
Comparative Effects of Nebivolol Versus Metoprolol on Sodium Sensitivity and Renal Sodium Handling in Hypertensive Hispanic Postmenopausal Women [NCT00992056]Phase 424 participants (Actual)Interventional2010-12-31Completed
Open-label, Multicenter, multinAtionaL, inteRventional Clinical Trial to Assess Efficacy and Safety of the exteMporaneous combInation of Nebivolol and Ramipril in hypertenSIve pAtients - ARTEMISIA Study [NCT06104423]Phase 4215 participants (Anticipated)Interventional2023-10-02Recruiting
A Multicenter, Open-Label, Single-Arm, Free Tablet Combination, Long-Term Study to Evaluate the Safety of Nebivolol in Combination With Valsartan in Patients With Stage 1 or Stage 2 Essential Hypertension [NCT01415505]Phase 3812 participants (Actual)Interventional2011-08-31Completed
A Double-Blind, Randomized, Multi-Center, Active Comparator, Five Treatment Study of the Effects of Nebivolol Compared to Atenolol on Cardiovascular Hemodynamics and Exercise Capacity in Patients With Mild to Moderate Hypertension [NCT00200421]Phase 2110 participants Interventional2002-05-31Completed
A Double-Blind, Multi-Center, Randomized, Placebo-Controlled, Parallel Group Dosing Study Evaluating the Effects of Nebivolol on Blood Pressure in Patients With Mild to Moderate Hypertension [NCT00200460]Phase 3825 participants Interventional2001-09-30Completed
A Multi-Center, Parallel Group Extension Study to Determine the Safety and Efficacy of Long-Term Nebivolol Exposure in Patients With Mild to Moderate Hypertension [NCT00200499]Phase 3845 participants Interventional2002-03-31Completed
The Surrogate Marker of Rate Control in Patients With Atrial Fibrillation [NCT04513509]50 participants (Anticipated)Interventional2020-08-07Not yet recruiting
Comparison the Effects of Nebivolol Versus Metoprolol Succinate on Endothelial Function and Large Artery Stiffness [NCT01248338]Phase 480 participants (Actual)Interventional2006-03-31Completed
Randomized, Multicenter, Observer-Masked Study to Compare Safety/Efficacy of Nebivolol Suspension 0.5% or 1.0%, or Timolol Suspension 0.5% to Timolol Solution 0.5% in Participants With Primary Open Angle Glaucoma or Ocular Hypertension [NCT04910100]Phase 2225 participants (Actual)Interventional2021-04-15Completed
The Evaluation of The Effects of Nebivolol in Comparison to Atenolol on Wall Shear Stress and Rupture Prone Coronary Artery Plaques in Patients With Moderate Coronary Artery Disease [NCT01230892]Phase 429 participants (Actual)Interventional2010-02-28Completed
An Advanced Echocardiographic Evaluation of Nebivolol [NCT01206439]Phase 42 participants (Actual)Interventional2010-09-30Terminated(stopped due to Slow enrollment)
Comparative Effect of Nebivolol vs. Metoprolol on Insulin Sensitivity and Fibrinolytic Balance in Metabolic Syndrome [NCT00775671]Phase 446 participants (Actual)Interventional2008-10-31Completed
The Efficacy and Tolerability of Highly Selective Beta-1 Agent in Hypertensive Black Patients Residing in Sub Saharan Africa: A Pilot Study [NCT03598673]200 participants (Actual)Observational2018-02-27Completed
A Double-Blind, Multicenter, Randomized, Placebo-Controlled, Parallel Group Dosing Study of the Effects of Nebivolol on Blood Pressure in Black Patients With Mild to Moderate Hypertension. [NCT00145236]Phase 3300 participants Interventional2001-11-30Completed
Comparative Effects of Nebivolol Versus Metoprolol on 24-hour Blood Pressures and Basal Metabolic Rate: An Open-Label Study [NCT00849810]1 participants (Actual)Interventional2009-01-31Terminated(stopped due to Difficulty with recruiting willing participants.)
Nebivolol Vs. Metoprolol: Comparative Effects on Fatigue and Quality of Life [NCT00999102]Phase 437 participants (Actual)Interventional2009-10-31Completed
Cognitive and Physical Impairment in Frail Older Adults [NCT04962841]485 participants (Anticipated)Observational2020-04-01Recruiting
Nebivolol Versus Bisoprolol Versus Carvedilol in Heart Failure: Effects on Exercise Capacity and Hypoxia, Chemoreceptor Response, Pulmonary Function [NCT00517725]Phase 460 participants (Actual)Interventional2007-07-31Completed
Evaluating the Outcome of Cardio Selective beta1- Blockers Use in Patients With Chronic Obstructive Pulmonary Disease: A Pilot Study [NCT04845061]Phase 430 participants (Anticipated)Interventional2021-10-01Recruiting
A Double-Blind, Randomized, Placebo- and Active-Controlled, Forced Titration Study Evaluating the Effects of Nebivolol on Blood Pressure and Heart Rate in African American Patients With Hypertension [NCT00145210]Phase 3630 participants (Anticipated)Interventional2005-04-30Completed
A Double-Blind, Multi-Center, Randomized, Placebo-Controlled, Parallel Group Study of the Effects of Nebivolol on Safety and Efficacy in Patients With Mild to Moderate Hypertension [NCT00200473]Phase 3800 participants Interventional2001-09-30Completed
The Pathophysiology and Treatment of Supine Hypertension in Patients With Autonomic Failure [NCT00223717]Phase 1152 participants (Actual)Interventional2001-01-31Completed
An Open Label, Randomized, 2 -Period, 2 -Treatment, 2- Sequence, Crossover, Single-Dose BE Study of Nebivolol 20 mg Tablet [Torrent, India] Vs Bystolic® 20 mg Tablet [ Forest Pharmaceuticals Inc., USA] in Healthy Subjects Fed Condition. [NCT03517033]Phase 130 participants (Actual)Interventional2011-05-31Completed
Efficacy and Tolerability of Nebivolol Compared With Carvedilol in Patients With Coronary Artery Disease and Stage I or II Hypertension [NCT00673075]Phase 439 participants (Actual)Interventional2008-05-31Completed
A Multicenter, Prospective, Randomized, Double-blind, Placebo-Controlled, Dose-Titration Study of Nebivolol Monotherapy in Hispanic Patients With Stage 1 or Stage 2 Hypertension [NCT00770861]Phase 4277 participants (Actual)Interventional2008-09-30Completed
Effect of Nebivolol and Lifestyle Modification on Large Artery Stiffness in Middle-Aged and Older Hypertensive Adults [NCT01920282]Phase 445 participants (Actual)Interventional2010-01-31Completed
Prognostic Value of Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy in Relation to Risk (the MAPEC Study). [NCT00295542]Phase 43,344 participants (Actual)Interventional2000-03-31Completed
Economic Impact of Switching From Metoprolol to Nebivolol for Hypertension Treatment: A Retrospective Database Analysis [NCT01758263]3,000 participants (Anticipated)Observational2012-10-31Active, not recruiting
Effects of Continuous Positive Airway Pressure (CPAP) and Nebivolol Treatment on Arterial Blood Pressure and Endothelial Function in Hypertensive OSA Patients. [NCT01771406]Phase 436 participants (Anticipated)Interventional2013-02-28Not yet recruiting
A Prospective, Randomized, Open-Label, 13 to 14-week Study of the Efficacy and Safety of Valsartan and Nebivolol/Valsartan in Hypertensive Subjects With Left Ventricular Hypertrophy (LVH) [NCT03180593]Phase 430 participants (Actual)Interventional2017-02-07Completed
Nebivolol and Endothelial Regulation of Fibrinolysis [NCT01595516]Phase 444 participants (Actual)Interventional2012-02-29Completed
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 [NCT01522950]Phase 276 participants (Actual)Interventional2010-05-31Completed
Open-laBel, Multicenter, multinatiOnal, inTerventional Clinical Trial to Assess effIcacy and Safety of the Extemporaneous Combination of nEbivoLol and amLodipine in Grade 1-2 Hypertensive patIents Versus Each Monotherapy [NCT05513937]Phase 4291 participants (Actual)Interventional2022-05-12Completed
Effect of Nebivolol on Blood Pressure in a Model of Hypertension Sensitive to Potentiation of Nitric Oxide Bioactivity [NCT01044693]20 participants (Actual)Interventional2010-01-31Completed
"An Open Label, 2-part, One-sequence, 3-period Study to Evaluate Drug-drug Interactions Between DWN12088 and Nebivolol or Paroxetine in Healthy Male Volunteers" [NCT04888728]Phase 124 participants (Actual)Interventional2021-06-30Completed
Effects of Nebivolol on Microvascular Perfusion in the Skeletal Muscles During Exercise in Hypertensive Patients [NCT01501929]Phase 432 participants (Actual)Interventional2010-08-31Completed
Effects of Nebivolol Versus Metoprolol on Blood Flow Responses to Exercise and Angiotensin II in Hypertensive Patients [NCT01502787]Phase 446 participants (Actual)Interventional2009-04-30Completed
The Effect of Nebivolol on Endothelial Dysfunction in African Americans With Hypertension [NCT01049009]Phase 491 participants (Actual)Interventional2009-12-31Completed
Nebivolol and the Endothelin (ET)-1 System [NCT01395329]Phase 442 participants (Actual)Interventional2011-05-31Completed
The Effects of Nebivolol on the NO-system in Patients With Essential [NCT01679652]Phase 225 participants (Actual)Interventional2012-08-31Completed
Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Effect of 5 mg or 20 mg Nebivolol Once Daily on Blood Pressure in Patients With Systolic Stage 2 Hypertension [NCT01057251]Phase 4433 participants (Actual)Interventional2010-03-31Completed
Effect of Nebivolol on Oxidative Stress and Endothelial Progenitor Cells in Subjects With Hypertension [NCT01041287]Phase 496 participants (Actual)Interventional2009-12-31Completed
The Impact of Nebivolol Versus Metoprolol on Quality of Life Measures and Cost-effectiveness in Stable Renal Transplant Recipients [NCT01441570]11 participants (Actual)Interventional2012-02-29Terminated(stopped due to due to slow enrollment)
Improving Treatment Personalization of Pulmonary Hypertension Associated With Diastolic Heart Failure [NCT02053246]Phase 411 participants (Actual)Interventional2014-01-31Terminated(stopped due to Study funding ended before recruitment completed.)
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Efficacy and Safety of Nebivolol in Younger Patients (18 - 54 Years) Who Have Stage 1 or 2 Essential Hypertension [NCT01415531]Phase 4641 participants (Actual)Interventional2011-08-31Completed
Alternative in Beta Blocker Intolerance; the ABBI Trial [NCT00893984]Phase 46 participants (Actual)Interventional2009-05-31Terminated(stopped due to Lack of patient recruitment)
Comparative Effects of Nebivolol and Metoprolol on Female Sexual Function [NCT00995072]29 participants (Actual)Interventional2009-10-31Completed
Nebivolol for the Relief of Microvascular Angina in Women [NCT01665508]Phase 412 participants (Actual)Interventional2013-04-30Completed
The Differential Effects of Antihypertensive Drugs on Central Blood Pressure: Comparison Between Beta-blocker and ARB [NCT05328310]110 participants (Anticipated)Interventional2019-01-06Active, not recruiting
Comparison of the Cardiovascular, Metabolic and Respiratory Effects of Nebivolol and Carvedilol at High Altitude in Healthy Subjects. [NCT00924833]Phase 427 participants (Actual)Interventional2006-05-31Completed
Ambulatory 24-Hour Cardiac Oxygen Consumption and Blood Pressure-Heart Rate Variability: Effects of Nebivolol and Valsartan Alone and in Combination [NCT05170061]Phase 326 participants (Actual)Interventional2013-02-28Completed
Effect of Nebivolol Compared With Metoprolol in Hypertensive Patients With Peripheral Arterial Disease [NCT01499134]Phase 317 participants (Actual)Interventional2011-08-31Completed
Effects of Nebivolol on Left Ventricular and Left Atrial Morphodynamics in Adults With Hypertension and Isolated Diastolic Dysfunction [NCT01961323]Phase 470 participants (Actual)Interventional2012-03-31Completed
Can Nebivolol Reverse Inappropriate Left Ventricular Mass in Hypertensive Patients? [NCT01605370]Phase 41 participants (Actual)Interventional2012-06-30Terminated(stopped due to Difficulty in identifying subjects satisfying the inclusion criteria.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00125853 (5) [back to overview]Total Cholesterol
NCT00125853 (5) [back to overview]HbA1c
NCT00125853 (5) [back to overview]Insulin Sensitivity Index (ISI)
NCT00125853 (5) [back to overview]BMI
NCT00125853 (5) [back to overview]24 Hour Systolic Blood Pressure
NCT00142584 (3) [back to overview]Number of Participants With Treatment Emergent Adverse Events (TEAEs)
NCT00142584 (3) [back to overview]Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline
NCT00142584 (3) [back to overview]Change in Average Sitting Diastolic Blood Pressure (DBP) Taken at Trough at the End of Treatment Compared to Baseline
NCT00673075 (4) [back to overview]Peripheral Systolic Blood Pressure (SBP)
NCT00673075 (4) [back to overview]Peripheral Diastolic Blood Pressure (DBP)
NCT00673075 (4) [back to overview]Proportion of Patients With Peripheral SBP <140 mm Hg and DBP <90 mm Hg at Week 18
NCT00673075 (4) [back to overview]Left Ventricular Ejection Fraction (LVEF) (%) at Week 18
NCT00673790 (2) [back to overview]Trough Seated Diastolic Blood Pressure
NCT00673790 (2) [back to overview]Plasma Glucose Level After an Oral Glucose Tolerance Test
NCT00734630 (2) [back to overview]Mean Seated Trough Cuff Systolic Blood Pressure (SBP) at Week 12
NCT00734630 (2) [back to overview]Mean Seated Trough Cuff Diastolic Blood Pressure (DBP) at Week 12
NCT00744237 (2) [back to overview]Change From Baseline in Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)
NCT00744237 (2) [back to overview]Change From Baseline in Mean Glycosylated Hemoglobin (HbA1c) at Week 26
NCT00770861 (2) [back to overview]Change From Baseline in Trough Seated Systolic Blood Pressure (SBP) at Week 8 (LOCF).
NCT00770861 (2) [back to overview]Change From Baseline in Trough Seated DBP at Week 8(LOCF).
NCT00775671 (2) [back to overview]Measurement of Insulin Sensitivity
NCT00775671 (2) [back to overview]Marker of Fibrinolysis
NCT00785512 (2) [back to overview]Trough Sitting Systolic Blood Pressure
NCT00785512 (2) [back to overview]Trough Sitting Diastolic Blood Pressure
NCT00829296 (4) [back to overview]Change in Pulse Wave Velocity (PWV)
NCT00829296 (4) [back to overview]Change in Central Systolic Blood Pressure (SBP)
NCT00829296 (4) [back to overview]Change in Augmentation Index
NCT00829296 (4) [back to overview]Change in Pulse Pressure Amplification
NCT00849810 (1) [back to overview]Primary Outcome is Pre- and Post-treatment Ambulatory Blood Pressure.
NCT00893984 (4) [back to overview]Number of Participants With Termination of Bystolic Stratified by Reason
NCT00893984 (4) [back to overview]Incidence of Same Symptom Stopping Bystolic as Previous Beta Blocker
NCT00893984 (4) [back to overview]Number of Participants With Intolerance of Bystolic, Measured by Side Effect(s) That Lead to Discontinuance of Bystolic by the Patient and/or the Physician
NCT00893984 (4) [back to overview]Number of Participants With Mild Symptoms
NCT00924833 (4) [back to overview]Peak Exercise Oxygen Consumption
NCT00924833 (4) [back to overview]Delta Peak Exercise Minute Ventilation Time 1 Versus Time 3.
NCT00924833 (4) [back to overview]Delta Peak Exercise Oxygen Consumption Time 1 Versus Time 3
NCT00924833 (4) [back to overview]Peak Exercise Minute Ventilation
NCT00992056 (1) [back to overview]Change in 24-hour Mean Systolic Blood Pressure by ABPM From Day 5 of Low Sodium to Day 10 of High Sodium
NCT00995072 (2) [back to overview]Change in Female Sexual Function Index
NCT00995072 (2) [back to overview]Change in Sexual Functioning Questionnaire Score
NCT00999102 (2) [back to overview]Treadmill Exercise Time After 4 Weeks of Treatment on Each Drug/Dose Combination.
NCT00999102 (2) [back to overview]Multidimensional Assessment of Fatigue (MAF) Questionnaire: Global Fatigue Score After 4 Weeks of Treatment on Each Drug/Dose Combination.
NCT01041287 (3) [back to overview]Pulse Wave Velocity (Measure of Arterial Stiffness)
NCT01041287 (3) [back to overview]Pulse Wave Velocity (Measure of Arterial Stiffness)
NCT01041287 (3) [back to overview]Pulse Wave Velocity (Measure of Arterial Stiffness)
NCT01044693 (4) [back to overview]Change in Heart Rate During the Night
NCT01044693 (4) [back to overview]Nocturnal Urinary Sodium Excretion
NCT01044693 (4) [back to overview]Orthostatic Tolerance the Following Morning
NCT01044693 (4) [back to overview]Change in Systolic Blood Pressure During the Night
NCT01049009 (2) [back to overview]Endothelial Function Measured by Forearm Blood Flow (FBF) at 12 Weeks
NCT01049009 (2) [back to overview]Endothelial Function Measured by Forearm Blood Flow (FBF) at 24 Weeks
NCT01056718 (27) [back to overview]LV Mass
NCT01056718 (27) [back to overview]Metabolic Equivalent (METS) Level
NCT01056718 (27) [back to overview]Mitral Valve E/A Ratio
NCT01056718 (27) [back to overview]Mitral Valve Inflow (A) Velocity
NCT01056718 (27) [back to overview]Mitral Valve Inflow (E) Velocity
NCT01056718 (27) [back to overview]Mitral Valve Tissue Doppler Velocity (a')
NCT01056718 (27) [back to overview]Mitral Valve Tissue Doppler Velocity (e')
NCT01056718 (27) [back to overview]Peak Stress Diastolic BP
NCT01056718 (27) [back to overview]Peak Stress Systolic BP
NCT01056718 (27) [back to overview]Pulmonary Vein Peak Diastolic Velocity
NCT01056718 (27) [back to overview]Pulmonary Vein Peak Systolic Velocity
NCT01056718 (27) [back to overview]Quality of Life
NCT01056718 (27) [back to overview]Resting Cardiac Output
NCT01056718 (27) [back to overview]Resting EF
NCT01056718 (27) [back to overview]Resting Heart Rate
NCT01056718 (27) [back to overview]Resting Stroke Volume
NCT01056718 (27) [back to overview]Resting Systolic BP
NCT01056718 (27) [back to overview]Stress Cardiac Output
NCT01056718 (27) [back to overview]Stress EF
NCT01056718 (27) [back to overview]Stress Heart Rate
NCT01056718 (27) [back to overview]Stress Stroke Volume
NCT01056718 (27) [back to overview]Mitral Valve Deceleration Time
NCT01056718 (27) [back to overview]Diastolic BP
NCT01056718 (27) [back to overview]E/e' Ratio
NCT01056718 (27) [back to overview]Exercise Duration
NCT01056718 (27) [back to overview]LV End Diastolic Diameter
NCT01056718 (27) [back to overview]LV End Systolic Diameter
NCT01057251 (2) [back to overview]Change From Baseline in Mean Seated Diastolic Blood Pressure After 6 Weeks of Nebivolol Monotherapy
NCT01057251 (2) [back to overview]Change From Baseline in Mean Seated Systolic Blood Pressure After 6 Weeks of Nebivolol Monotherapy
NCT01157234 (11) [back to overview]Diastolic Blood Pressure (Millimeter, Mercury) Change From Baseline to Month-12 Between the Groups
NCT01157234 (11) [back to overview]Systolic Blood Pressure (Millimeter, Mercury) Change From Baseline to Month-12 of Treatment Between the Groups
NCT01157234 (11) [back to overview]Number of Antihypertensive Drug Classes Change From Baseline to Month-12 Between the Groups.
NCT01157234 (11) [back to overview]Percent Change in Plasma Nitric Oxide Level From Baseline to Month-12 of Treatment With Nebivolol in Transplant Recipients < 50 Years Old Compared With Metoprolol in Transplant Recipients < 50 Years Old
NCT01157234 (11) [back to overview]Percent Change in Plasma Nitric Oxide Level From Baseline to Month-12 of Treatment With Nebivolol in Transplant Recipients <50 Years Old Compared With Metoprolol in Transplant Recipients >/= 50 Years Old.
NCT01157234 (11) [back to overview]Percent Change in Plasma Nitric Oxide Level From Baseline to Month-12 of Treatment With Nebivolol in Transplant Recipients >/= 50 Years Old Compared With Metoprolol in Transplant Recipients Age >/= 50 Years Old.
NCT01157234 (11) [back to overview]Percent Change in Plasma Nitric Oxide Level From Baseline to Month-twelve of Treatment With Nebivolol in Transplant Recipients >/= 50 Years Old Compared With Nebivolol in Transplant Recipients < 50 Years Old.
NCT01157234 (11) [back to overview]Plasma Nitric Oxide Level (Nmol/L) at Month-12 Between the Groups.
NCT01157234 (11) [back to overview]Plasma Nitric Oxide Level Change From Baseline to Month 12 Between the Groups.
NCT01157234 (11) [back to overview]Mean Arterial Blood Pressure (Millimeter, Mercury) Change From Baseline to Month-12 Between the Groups
NCT01157234 (11) [back to overview]Estimated Glomerular Filtration Rate (ml/Minute) Change From Baseline to Month-12 Between the Groups
NCT01202175 (12) [back to overview]Urinary Hydrogen Peroxide Excretion
NCT01202175 (12) [back to overview]Urinary Isoprostane Excretion
NCT01202175 (12) [back to overview]Urinary Nitric Oxide Excretion
NCT01202175 (12) [back to overview]Aortic Augmentation Index for Heart Rate
NCT01202175 (12) [back to overview]Aortic Augmentation Pressure
NCT01202175 (12) [back to overview]Aortic Diastolic Blood Pressure (DBP)
NCT01202175 (12) [back to overview]Aortic Mean Arterial Pressure (MAP)
NCT01202175 (12) [back to overview]Aortic Pulse Pressure
NCT01202175 (12) [back to overview]Aortic Systolic Blood Pressure (SBP)
NCT01202175 (12) [back to overview]Heart Rate, Beats Per a Minute
NCT01202175 (12) [back to overview]Plasma Interleukin Levels
NCT01202175 (12) [back to overview]Pulse Wave Velocity
NCT01218100 (2) [back to overview]The Change From Baseline in Trough Seated Systolic Blood Pressure at Week 6.
NCT01218100 (2) [back to overview]The Change From Baseline in Trough Seated Diastolic Blood Pressure at Week 6.
NCT01230892 (1) [back to overview]Number of Participants With Reduction of Thin-cap Fibroatheromas (TCFA) as Defined by VH-IVUS
NCT01395329 (7) [back to overview]Diastolic Blood Pressure
NCT01395329 (7) [back to overview]Systolic Blood Pressure
NCT01395329 (7) [back to overview]FBF Response to Acetylcholine (ACh)
NCT01395329 (7) [back to overview]FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788)
NCT01395329 (7) [back to overview]FBF Response to Sodium Nitroprusside
NCT01395329 (7) [back to overview]Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min)
NCT01395329 (7) [back to overview]Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min)
NCT01415531 (2) [back to overview]Trough Seated Systolic Blood Pressure (SBP)
NCT01415531 (2) [back to overview]Trough Seated Diastolic Blood Pressure (DBP)
NCT01441570 (2) [back to overview]Quality of Life
NCT01441570 (2) [back to overview]Blood Pressure
NCT01499134 (8) [back to overview]Walking Impairment Questionnaire (WIQ) - Change in WIQ Distance Score
NCT01499134 (8) [back to overview]Walking Impairment Questionnaire (WIQ) - Change in Buttock Pain
NCT01499134 (8) [back to overview]Peak Walking Time (PWT)
NCT01499134 (8) [back to overview]Claudication Onset Time (COT)
NCT01499134 (8) [back to overview]Ankle-brachial Index (ABI)
NCT01499134 (8) [back to overview]Walking Impairment Questionnaire (WIQ) - Change Calf Pain
NCT01499134 (8) [back to overview]Walking Impairment Questionnaire (WIQ) - Change in WIQ Speed Score
NCT01499134 (8) [back to overview]Walking Impairment Questionnaire (WIQ) - Change in WIQ Stairs Score
NCT01501929 (2) [back to overview]Endothelial Cell Protein Expression p47phox From Endothelial Cell Collection
NCT01501929 (2) [back to overview]Microvascular Blood Flow
NCT01502787 (3) [back to overview]Blood Pressure During Angiotensin II Infusion
NCT01502787 (3) [back to overview]Blood Pressure During Exercise
NCT01502787 (3) [back to overview]Forearm Blood Flow
NCT01522950 (4) [back to overview]Change in Diastolic Blood Pressure
NCT01522950 (4) [back to overview]Change in Large Artery Elasticity
NCT01522950 (4) [back to overview]Change in Small Artery Elasticity
NCT01522950 (4) [back to overview]Change in Systolic Blood Pressure
NCT01595516 (6) [back to overview]Diastolic Blood Pressure
NCT01595516 (6) [back to overview]Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy.
NCT01595516 (6) [back to overview]Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention
NCT01595516 (6) [back to overview]Heart Rate
NCT01595516 (6) [back to overview]Systolic Blood Pressure
NCT01595516 (6) [back to overview]Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy.
NCT01665508 (6) [back to overview]Exercise Duration
NCT01665508 (6) [back to overview]Peak Heart Rate as Measured by Cardiopulmonary Exercise Testing
NCT01665508 (6) [back to overview]Peak O2 Pulse
NCT01665508 (6) [back to overview]Peak VO2 Measured by Cardiopulmonary Exercise Testing
NCT01665508 (6) [back to overview]Seattle Angina Questionnaire Score
NCT01665508 (6) [back to overview]SF36
NCT01920282 (2) [back to overview]Insulin Sensitivity (HOMA-IR)
NCT01920282 (2) [back to overview]Beta-stiffness Index
NCT01961323 (3) [back to overview]Untwist Rate of the Left Ventricle
NCT01961323 (3) [back to overview]E Velocity Indexed to e' (E/e' Ratio) of the Left Ventricle
NCT01961323 (3) [back to overview]Improvement in Exercise Tolerance
NCT02053246 (2) [back to overview]Changes in Pulmonary Vascular Pressure
NCT02053246 (2) [back to overview]Changes in 6-minute Walk Distance
NCT02710071 (1) [back to overview]24-h, Wake and Sleep Period Systolic and Diastolic Blood Pressure
NCT04767061 (10) [back to overview]Change in Patient-reported Quality of Life When on Beta-blocker Versus When Off Beta-blocker, as Measured by Patient-Reported Outcome Measurement Information System-29 (PROMIS-29)
NCT04767061 (10) [back to overview]Change in Patient-reported Sexual Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by Patient-Reported Outcome Measurement Information System-Sexual Function (PROMIS-Sexual Function)
NCT04767061 (10) [back to overview]Change in Patient-reported Health Status When on Beta-blocker Versus When Off Beta-blocker, as Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
NCT04767061 (10) [back to overview]Change in Patient-reported Health When on Beta-blocker Versus When Off Beta-blocker, as Measured by the EuroQol-5D Visual Analogue System (EQ-5D VAS)
NCT04767061 (10) [back to overview]Change in Patient-reported Cognitive Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by Patient-Reported Outcome Measurement Information System-Short Form 6a (PROMIS SF-6a)
NCT04767061 (10) [back to overview]Change in Physical Activity When on Beta-blocker Versus When Off Beta-blocker, as Measured by Step Count on Wearable Activity Monitoring Device
NCT04767061 (10) [back to overview]Change in Exercise Capacity When on Beta-blocker Versus When Off Beta-blocker, as Measured by Peak Oxygen Consumption (VO2) During Cardiopulmonary Exercise Test (CPET)
NCT04767061 (10) [back to overview]Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Balance Portion of a Modified Version of the Short Physical Performance Battery.
NCT04767061 (10) [back to overview]Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Gait Speed Portion of a Modified Version of the Short Physical Performance Battery.
NCT04767061 (10) [back to overview]Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Chair Rise Portion of a Modified Version of the Short Physical Performance Battery.

Total Cholesterol

Fasting blood samples were taken at the beginning and end of each treatment period. (NCT00125853)
Timeframe: Before and after 8 weeks of treatment

,
Interventionmmol/L (Mean)
BeforeAfter
Atenolol5.04.9
Nebivolol5.15.1

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HbA1c

Fasting blood samples were taken at the beginning and end of each treatment period. (NCT00125853)
Timeframe: Before and after 8 weeks of treatment

,
Interventionpercentage of glycosylated hemoglobin (Mean)
BeforeAfter
Atenolol5.75.7
Nebivolol5.75.7

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Insulin Sensitivity Index (ISI)

"Patients were asked to fast for a minimum of 12 hours prior to each oral glucose tolerance test (OGTT). Venous blood was withdrawn for insulin and glucose analysis, 15 minutes and immediately prior to, and 30, 60, 90 and 120 minutes following an oral glucose load. For each OGTT, the Insulin Sensitivity Index (ISI) was calculated using the standard method for oral glucose tolerance testing.~For each OGTT, the Insulin Sensitivity Index (ISI) was calculated using the standard method for oral glucose tolerance testing." (NCT00125853)
Timeframe: Baseline, 15, 30, 60, 90, 120m following oral glucose load, at baseline and at the end of each phase(8 weeks treatment

,
Interventionfactor (Mean)
BeforeAfter
Atenolol82.3675.47
Nebivolol80.7081.54

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BMI

Body weights and heights were taken at the beginning and end of each treatment period. (NCT00125853)
Timeframe: Before and after 8 weeks of treatment

,
Interventionkg/m^2 (Mean)
BeforeAfter
Atenolol28.128.0
Nebivolol28.228.3

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24 Hour Systolic Blood Pressure

The 24-h Ambulatory Blood Pressure Monitoring (ABPM) was recorded at the beginning and end of each beta-blocker treatment period. BP was automatically recorded for 24 h at 30 min intervals. The time periods from 0700h to 2200h and from 2200h to 0700h were defined as daytime and night-time, respectively. (NCT00125853)
Timeframe: Before and after 8 weeks of treatment

,
InterventionmmHg (Mean)
SBP beforeSBP after
Atenolol128.4117.2
Nebivolol130.4121.2

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Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Summary of Participants that experienced one or more TEAEs by Treatment Group-Safety Population (NCT00142584)
Timeframe: Through study completion (approximately 18 months)

InterventionParticipants (Count of Participants)
1-NEB150
2-MET51

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Change From Baseline in Mean Trough Sitting Diastolic Blood Pressure (DBP) at Each Study Visit (Visits 1 Through 9) Compared to Baseline

Data for the analysis of the change from baseline in mean trough sitting DBP at each study visit (Visits 1 through 9) compared with baseline (baseline was defined as the baseline visit in Study NEB 310 [NCT00145210]) by treatment group are provided below. (NCT00142584)
Timeframe: Through study completion (approximately 18 months)

,
Interventionmm Hg (Mean)
Visit 1Visit 2Visit 3Visit 4Visit 5Visit 6Visit 7Visit 8Visit 9
1-NEB-8.3-8.4-10.6-12.1-13.0-14.5-15.5-16.3-16.7
2-MET-8.4-8.4-9.8-10.7-12.4-12.1-13.1-12.4-13.7

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Change in Average Sitting Diastolic Blood Pressure (DBP) Taken at Trough at the End of Treatment Compared to Baseline

The primary efficacy parameter was the change in the average trough sitting DBP at the end of treatment (Visit 10 or Early Termination) compared with baseline (baseline was defined as the baseline visit in Study NEB 310 [NCT00145210]). (NCT00142584)
Timeframe: Through study duration (approximately 18 months)

Interventionmm Hg (Mean)
1-NEB-14.0
2-MET-10.9

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Peripheral Systolic Blood Pressure (SBP)

Peripheral systolic blood pressure (SBP) at visit 13 (week 18) (NCT00673075)
Timeframe: 18 weeks post initiation of randomized treatment

,
InterventionmmHg (Mean)
BaselinePost-Baseline
Carvedilol136.9137.3
Nebivolol135.1129.6

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Peripheral Diastolic Blood Pressure (DBP)

Peripheral diastolic blood pressure (DBP) at post-baseline (visit 13, week 18) (NCT00673075)
Timeframe: 18 weeks post initiation of randomized treatment

,
InterventionmmHg (Mean)
BaselinePost-baseline
Carvedilol78.279.3
Nebivolol81.178.0

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Proportion of Patients With Peripheral SBP <140 mm Hg and DBP <90 mm Hg at Week 18

Proportion of Patients with Peripheral SBP <140 mm Hg and DBP <90 mm Hg at Week 18 (NCT00673075)
Timeframe: 18 weeks post-treatment

Interventionparticipants (Number)
Nebivolol11
Carvedilol5

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Left Ventricular Ejection Fraction (LVEF) (%) at Week 18

Left ventricular ejection fraction (LVEF) (%) at Week 18 (NCT00673075)
Timeframe: 18 weeks post-treatment

,
Interventionpercentage (Mean)
BaselinePost baseline
Carvedilol60.44260.775
Nebivolol61.4361.93

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Trough Seated Diastolic Blood Pressure

Change from Baseline in Mean Seated Trough Cuff Diastolic Blood Pressure (DBP) at Week 12, Last Observation Carried Forward (LOCF). (NCT00673790)
Timeframe: Change from Baseline Visit 4 (Week 0) To Visit 8 (Week 12)

Interventionmm Hg (Mean)
Nebivolol-9.4
Placebo-5.0

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Plasma Glucose Level After an Oral Glucose Tolerance Test

Change from Baseline in Plasma Glucose 2 Hours Post-oral Glucose 75 grams, given as part of an Oral Glucose Tolerance Test (OGTT). Last Observation Carried Forward. (NCT00673790)
Timeframe: Change from Baseline Visit 3 or 4 (Week -2 or 0) To Visit 8 (Week 12)

Interventiong/mL (Least Squares Mean)
Nebivolol0.20
Hydrochlorothiazide (HCTZ)0.31
Placebo-0.21

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Mean Seated Trough Cuff Systolic Blood Pressure (SBP) at Week 12

Change from Baseline in Mean Seated Trough Cuff Systolic Blood Pressure (SBP) at Week 12, Last Observation Carried Forward (LOCF). (NCT00734630)
Timeframe: From baseline Visit 5 (Week 0) to Visit 10 (Week 12)

InterventionmmHG (Mean)
Nebivolol-10.1
Placebo-7.3

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Mean Seated Trough Cuff Diastolic Blood Pressure (DBP) at Week 12

Change from Baseline in Mean Seated Trough Cuff Diastolic Blood Pressure (DBP) at Week 12, Last Observation Carried Forward (LOCF). (NCT00734630)
Timeframe: From baseline Visit 5 (Week 0) to Visit 10 (Week 12)

InterventionmmHG (Mean)
Nebivolol-7.8
Placebo-3.5

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Change From Baseline in Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)

Change from Baseline in Insulin Resistance based on homeostasis model assessment of insulin resistance (HOMA-IR) at week 26, Last Observation Carried Forward (LOCF). The HOMA-IR is the the product of the blood Glucose and Insulin levels, divided by a constant. HOMA-IR is expressed as the following: HOMA-IR = fasting serum insulin (μU/ml) × fasting plasma glucose (mmol/l) / 22.5 (NCT00744237)
Timeframe: [visit 5(week 0) and visit 14(week 26)]

InterventionUnit on a scale (Mean)
Nebivolol0.011
Metoprolol ER1.156
Hydrochlorothiazide (HCTZ)-0.662

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Change From Baseline in Mean Glycosylated Hemoglobin (HbA1c) at Week 26

Change from baseline in glycosylated hemoglobin (HbA1c) over 26 weeks, Last Observation Carried Forward. (NCT00744237)
Timeframe: visit 5(week 0) and visit 14(week 26)

InterventionPercentage (Mean)
Nebivolol0.12
Metoprolol ER0.00
Hydrochlorothiazide (HCTZ)0.40

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Change From Baseline in Trough Seated Systolic Blood Pressure (SBP) at Week 8 (LOCF).

The secondary efficacy parameter was the change from baseline in mean trough seated SBP at Week 8. The average of three consecutive BP measurements would be the mean trough seated SBP value. (NCT00770861)
Timeframe: From baseline visit 7 (week 0) to end of double-blind treatment phase visit 11 (week 8)

Interventionmm Hg (Mean)
Nebivolol-14.1
Placebo-9.3

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Change From Baseline in Trough Seated DBP at Week 8(LOCF).

The primary efficacy parameter was the change from baseline in mean trough seated DBP at Week 8. The average of three consecutive BP measurements would be the mean trough seated DBP value. (NCT00770861)
Timeframe: From baseline visit 7 (week 0) to end of double-blind treatment phase visit 11 (week 8)

Interventionmm Hg (Mean)
Nebivolol-11.1
Placebo-7.3

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Measurement of Insulin Sensitivity

The change in insulin sensitivity index, from baseline to after 12 weeks of treatment. Calculated from the intravenous glucose tolerance test at baseline and at 12 weeks. (NCT00775671)
Timeframe: 3 hours

Intervention10-4xmin-1 per mU/L (Mean)
Nebivolol0.04
Metoprolol-1.5

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Marker of Fibrinolysis

Concentration of plasminogen activator inhibitor 1 (PAI-1)antigen. (NCT00775671)
Timeframe: After 12 weeks of study drug

Interventionng/mL (Mean)
Nebivolol10.5
Metoprolol12.3

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Trough Sitting Systolic Blood Pressure

Change from baseline, week 0 (Visit 9) to Week 4 (Visit 12) in peripheral systolic blood pressure measured at drug trough. (NCT00785512)
Timeframe: From baseline, week 0 (Visit 9) to week 4 (Visit 12)

,
Interventionmm HG (Mean)
BaselineChange from baseline
Nebivolol134.13.5
Placebo134.47.6

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Trough Sitting Diastolic Blood Pressure

Change from baseline, week 0 (Visit 9) to Week 4 (Visit 12) in peripheral diastolic blood pressure measured at drug trough. (NCT00785512)
Timeframe: From baseline, week 0 (Visit 9) to week 4 (Visit 12)

,
Interventionmm HG (Mean)
BaselineChange from baseline
Nebivolol81.31.8
Placebo81.17.7

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Change in Pulse Wave Velocity (PWV)

To examine the effect of nebivolol versus metoprolol succinate in Type 2 hypertensive diabetic patients on other measures of central conduit artery function such as pulse wave velocity. (NCT00829296)
Timeframe: Baseline and 26 Weeks

,
Interventionm/s (Mean)
Pulse wave velocity at BaselinePulse wave velocity at 26 Weeks
Metoprolol6.526.4
Nebivolol6.486.3

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Change in Central Systolic Blood Pressure (SBP)

Changes in aortic impedance in patients on nebivolol vs. metoprolol succinate in Type 2 hypertensive diabetic patients as measured by the change from baseline in central systolic blood pressure. (NCT00829296)
Timeframe: Baseline and 26 Weeks

,
InterventionmmHg (Mean)
Aortic Systolic Blood Pressure at BaselineAortic Systolic Blood Pressure at 26 Weeks
Metoprolol127.8123.8
Nebivolol125.3121.6

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Change in Augmentation Index

Augmentation index is defined as the percentage of the central pulse pressure which is attributed to the reflected pulse wave and, therefore, reflects the degree to which central arterial pressure is augmented by wave reflection. (NCT00829296)
Timeframe: Baseline and 26 Weeks

,
Interventionpercent (%) (Mean)
Augmentation index at BaselineAugmentation index at 26 Weeks
Metoprolol26.224.6
Nebivolol22.022.1

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Change in Pulse Pressure Amplification

To examine the effect of nebivolol versus metoprolol succinate in Type 2 hypertensive diabetic patients on other measures of central conduit artery function such as pulse pressure amplification (central pulse pressure /brachial pulse pressure). (NCT00829296)
Timeframe: Baseline and 26 Weeks

,
Interventionratio (Mean)
Pulse pressure amplification at BaselinePulse pressure amplification at 26 Weeks
Metoprolol0.790.85
Nebivolol0.770.83

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Primary Outcome is Pre- and Post-treatment Ambulatory Blood Pressure.

(NCT00849810)
Timeframe: 4 weeks (pre- and post-treatment)

Interventionmm HG (Mean)
SBP ABPM on metoprololDBP ABPM on metoprololSBP ABPM on nebivololDBP ABPM on nebivolol
Metoprolol to Nebivolol1227212271

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Number of Participants With Termination of Bystolic Stratified by Reason

(NCT00893984)
Timeframe: 30 Days

InterventionParticipants (Count of Participants)
Nebivolol0

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Number of Participants With Intolerance of Bystolic, Measured by Side Effect(s) That Lead to Discontinuance of Bystolic by the Patient and/or the Physician

(NCT00893984)
Timeframe: 30 Days

InterventionParticipants (Count of Participants)
Nebivolol0

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Number of Participants With Mild Symptoms

Mild symptoms include weight gain, edema, and headaches (NCT00893984)
Timeframe: 30 Days

Interventionparticipants (Number)
Nebivolol1

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Peak Exercise Oxygen Consumption

Oxygen consumption at peak of exercise (NCT00924833)
Timeframe: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.

,,
Interventionml/Kg/min (Mean)
Time 1Time 2Time 3
Carvedilol37.636.224.0
Nebivolol38.039.728.8
Placebo33.933.922.9

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Delta Peak Exercise Minute Ventilation Time 1 Versus Time 3.

"Difference in peak exercise minute ventilation between Time 1 and Time 3 (Time 3 - Time 1.~Minute ventilation = tidal volume (ml) multiplied by the respiratory rate (breaths/min)." (NCT00924833)
Timeframe: Time 1: sea level, baseline, no treatment. Time 3: within the first two days of high altitude exposure, under treatment.

InterventionL/min (Mean)
Placebo0.7
Carvedilol-9.3
Nebivolol15.2

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Delta Peak Exercise Oxygen Consumption Time 1 Versus Time 3

Difference in peak exercise oxygen consumption between Time 1 and Time 3 (Time 3 - Time 1) (NCT00924833)
Timeframe: Time 1: sea level, baseline, no treatment. Time 3: within the first two days of high altitude exposure, under treatment.

Interventionml/Kg/min (Mean)
Placebo-32.7
Carvedilol-37.6
Nebivolol-22.5

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Peak Exercise Minute Ventilation

Minute ventilation at peak of exercise. Minute ventilation = tidal volume (ml) multiplied by the respiratory rate (breaths/min) (NCT00924833)
Timeframe: Time 1: sea level, baseline, no treatment. Time 2: sea level, after three weeks of allocated treatment. Time 3: within the first two days of high altitude exposure, under treatment.

,,
InterventionL/min (Mean)
Time 1Time 2Time 3
Carvedilol90.389.684.5
Nebivolol81.883.892.0
Placebo93.995.690.3

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Change in 24-hour Mean Systolic Blood Pressure by ABPM From Day 5 of Low Sodium to Day 10 of High Sodium

(NCT00992056)
Timeframe: Day 5, Day 10

InterventionmmHg (Mean)
Metoprolol7.7
Nebivolol9.3

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Change in Female Sexual Function Index

This scale is a self-reported instrument used to detect female sexual function. The scale ranges from 2 to 36. The higher score indicates higher sexual function. (NCT00995072)
Timeframe: Baseline, 12 weeks

Interventionunits on a scale (Mean)
Nebivolol 5 mg Daily1.24
Metoprolol Succinate 100 mg Daily1.42

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Change in Sexual Functioning Questionnaire Score

This scale is a self-reported instrument used to detect sexual functioning. The scale ranges from 14 to 70. The higher scores reflects higher sexual functioning. (NCT00995072)
Timeframe: Baseline, 12 weeks

Interventionunits on a scale (Mean)
Nebivolol 5 mg Daily2.38
Metoprolol Succinate 100 mg Daily0.85

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Treadmill Exercise Time After 4 Weeks of Treatment on Each Drug/Dose Combination.

Treadmill Exercise Time After 4 Weeks of Treatment on Each Drug/Dose Combination (in minutes). The Treadmill Test was Performed at the 4-week Visit of Each Drug/Dose Combination. (NCT00999102)
Timeframe: After 4 weeks of treatment on each drug/dose combination

Interventionminutes (Mean)
Nebivolol 5 mg for 4 Weeks833.9
Metoprolol 50 mg for 4 Weeks840.9
Nebivolol 10 mg for 4 Weeks841.2
Metoprolol 100 mg for 4 Weeks867.1

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Multidimensional Assessment of Fatigue (MAF) Questionnaire: Global Fatigue Score After 4 Weeks of Treatment on Each Drug/Dose Combination.

"A 16 item scale that measures 4 dimensions of fatigue: severity, distress, timing, and degree of interference in activities of daily living.~Range: 1 (no fatigue) to 50 (extreme fatigue)." (NCT00999102)
Timeframe: After 4 weeks of treatment on each drug/dose combination

Interventionunits on a scale (Mean)
Nebivolol 5 mg for 4 Weeks18.5
Metoprolol 50 mg for 4 Weeks18.0
Nebivolol 10 mg for 4 Weeks21.0
Metoprolol 100 mg for 4 Weeks20.3

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Pulse Wave Velocity (Measure of Arterial Stiffness)

The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s). (NCT01041287)
Timeframe: 3 months

Interventionmeters per second (m/s) (Mean)
Nebivolol/ Metoprolol8.4
Metoprolol/Nebivolol10.1

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Pulse Wave Velocity (Measure of Arterial Stiffness)

The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s). (NCT01041287)
Timeframe: Baseline

Interventionmeters per second (m/s) (Mean)
Nebivolol/ Metoprolol9.4
Metoprolol/Nebivolol8.9

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Pulse Wave Velocity (Measure of Arterial Stiffness)

The pulse wave velocity (PWV) system measured the velocity of the blood pressure waveform between the carotid and femoral arteries using a single-lead electrocardiogram and tonometer to measure the pressure pulse waveform sequentially at the two peripheral artery sites. PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s). (NCT01041287)
Timeframe: 6 months

Interventionmeters per second (m/s) (Mean)
Nebivolol/ Metoprolol9.1
Metoprolol/Nebivolol9.8

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Change in Heart Rate During the Night

Change from baseline (8 pm) in heart rate at the time of maximal BP-lowering effect (NCT01044693)
Timeframe: 8 pm - 8 am

Interventionbpm (Mean)
Placebo Capsule-3
Nebivolol 5 mg-6
Metoprolol Tartrate 50 mg-6
Sildenafil 25 mg0

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Nocturnal Urinary Sodium Excretion

Nocturnal sodium excretion was defined as the ratio of urinary sodium to urinary creatinine. (NCT01044693)
Timeframe: 8 pm - 8 am

InterventionmEq/mg (Mean)
Placebo Capsule0.145
Nebivolol 5 mg0.127
Metoprolol Tartrate 50 mg0.139
Sildenafil 25 mg0.125

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Orthostatic Tolerance the Following Morning

Orthostatic tolerance was defined as the area under the curve of standing systolic blood pressure calculated by the trapezoidal rule (upright systolic blood pressure multiplied by standing time) during a 10-minute standing test (NCT01044693)
Timeframe: 10 min standing

Interventionmm Hg*min (Mean)
Placebo Capsule594
Nebivolol 5 mg675
Metoprolol Tartrate 50 mg696
Sildenafil 25 mg575

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Change in Systolic Blood Pressure During the Night

Maximal change from baseline in systolic blood pressure, measured from 8 pm to 8 am, after a single dose of the intervention (NCT01044693)
Timeframe: 8 pm - 8 am

,,,
Interventionmm Hg (Mean)
Baseline supine at 8 pmChange in systolic BP
Metoprolol Tartrate 50 mg157-7
Nebivolol 5 mg162-24
Placebo Capsule1541
Sildenafil 25 mg158-20

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Endothelial Function Measured by Forearm Blood Flow (FBF) at 12 Weeks

Forearm blood flow measured by venous occlusion plethysmography at rest, after administration of N(G)-monomethyl-L-arginine (L-NMMA) and tetraethylammonium chloride (TEA), after administration of L-NMMA, TEA, and acetylcholine, and after administration of L-NMMA, TEA, and exercise. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute. (NCT01049009)
Timeframe: 12 weeks

,
InterventionmL/100 mL/min (Mean)
At restL-NMMA+TEAL-NMMA+TEA+AChL-NMMA+TEA+exercise
Metoprolol XL/Nebivolol2.6792.2217.56211.574
Nebivolol/Metoprolol XL2.7391.9635.3767.377

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Endothelial Function Measured by Forearm Blood Flow (FBF) at 24 Weeks

Forearm blood flow measured by venous occlusion plethysmography at rest, after administration of N(G)-monomethyl-L-arginine (L-NMMA) and tetraethylammonium chloride (TEA), after administration of L-NMMA, TEA, and acetylcholine, and after administration of L-NMMA, TEA, and exercise. Unit of Measure refers to volume of blood (mL) per 100 mL of forearm tissue per minute. (NCT01049009)
Timeframe: 24 weeks

,
InterventionmL/100 mL/min (Mean)
At restL-NMMA+TEAL-NMMA+TEA+AChL-NMMA+TEA+exercise
Metoprolol XL/Nebivolol2.9682.2877.53410.395
Nebivolol/Metoprolol XL3.0662.4577.1589.589

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LV Mass

(NCT01056718)
Timeframe: 10 week

Interventiongrams (Mean)
Nebivolol Treatment167

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Metabolic Equivalent (METS) Level

METs is a measure of exercise capacity. One MET is defined as 3.5 mL 02 uptake/kg per minute which is the resting oxygen uptake in a sitting position. The Bruce protocol consisted of successive 3 minute stages each of which requires the subject to walk at a faster speed and higher grade of incline. Each stage is assigned a MET level. The achieved exercise capacity in METs has been shown to be predictive in older adult population of survival with higher MET levels associated with improved survival. (NCT01056718)
Timeframe: 10 Weeks

InterventionMETS (Mean)
Nebivolol Treatment6.7

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Mitral Valve E/A Ratio

mitral valve doppler E velocity to A velocity (NCT01056718)
Timeframe: 10 Week

InterventionRatio (Mean)
Nebivolol Treatment0.97

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Mitral Valve Inflow (A) Velocity

(NCT01056718)
Timeframe: 10 Week

Interventioncm/s (Mean)
Nebivolol Treatment90

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Mitral Valve Inflow (E) Velocity

(NCT01056718)
Timeframe: 10 Week

Interventioncm/s (Mean)
Nebivolol Treatment85

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Mitral Valve Tissue Doppler Velocity (a')

(NCT01056718)
Timeframe: 10 Week

Interventioncm/s (Mean)
Nebivolol Treatment11.5

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Mitral Valve Tissue Doppler Velocity (e')

(NCT01056718)
Timeframe: 10 Week

Interventioncm/s (Mean)
Nebivolol Treatment8.7

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Peak Stress Diastolic BP

(NCT01056718)
Timeframe: 10 Week

Interventionmm Hg (Mean)
Nebivolol Treatment68

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Peak Stress Systolic BP

(NCT01056718)
Timeframe: 10 Week

Interventionmm Hg (Mean)
Nebivolol Treatment171

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Pulmonary Vein Peak Diastolic Velocity

(NCT01056718)
Timeframe: 10 Week

Interventioncm/s (Mean)
Nebivolol Treatment51

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Pulmonary Vein Peak Systolic Velocity

(NCT01056718)
Timeframe: 10 Week

Interventioncm/s (Mean)
Nebivolol Treatment63

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Quality of Life

"Quality of life was assessed by a visual analogue scale before and after 10 weeks of nebivolol. The subjects self reported assessment of his/her overall health was recorded on a vertical visual analogue scale where 100 is the best imaginable health state and 0 is the worst imaginable health state." (NCT01056718)
Timeframe: 10 Weeks

Interventionunits on a scale (Mean)
Nebivolol Treatment78

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Resting Cardiac Output

(NCT01056718)
Timeframe: 10 week

InterventionL per minute (Mean)
Nebivolol Treatment3.0

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Resting EF

(NCT01056718)
Timeframe: 10 Weeks

InterventionPercent of LV end diastolic volume (Mean)
Nebivolol Treatment63

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Resting Heart Rate

(NCT01056718)
Timeframe: 10 Week

InterventionBeats per Minute (Mean)
Nebivolol Treatment65

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Resting Stroke Volume

(NCT01056718)
Timeframe: 10 weeks

Interventionml (Mean)
Nebivolol Treatment48

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Resting Systolic BP

(NCT01056718)
Timeframe: 10 Weeks

Interventionmm Hg (Mean)
Nebivolol Treatment135

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Stress Cardiac Output

(NCT01056718)
Timeframe: 10 week

InterventionL per minute (Mean)
Nebivolol Treatment5.3

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Stress EF

(NCT01056718)
Timeframe: 10 Week

InterventionPercent of LV end diastolic volume (Mean)
Nebivolol Treatment72

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Stress Heart Rate

(NCT01056718)
Timeframe: 10 Week

InterventionBeats per Minute (Mean)
Nebivolol Treatment118

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Stress Stroke Volume

(NCT01056718)
Timeframe: 10 week

Interventionml (Mean)
Nebivolol Treatment51

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Mitral Valve Deceleration Time

(NCT01056718)
Timeframe: 10 Week

Interventionms (Mean)
Nebivolol Treatment227

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Diastolic BP

(NCT01056718)
Timeframe: 10 Week

Interventionmm Hg (Mean)
Nebivolol Treatment76

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E/e' Ratio

(NCT01056718)
Timeframe: 10 Week

InterventionRatio (Mean)
Nebivolol Treatment10.5

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Exercise Duration

(NCT01056718)
Timeframe: 10 Weeks

InterventionSeconds (Mean)
Nebivolol Treatment419

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LV End Diastolic Diameter

(NCT01056718)
Timeframe: 10 week

Interventioncm (Mean)
Nebivolol Treatment4.8

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LV End Systolic Diameter

(NCT01056718)
Timeframe: 10 week

Interventioncm (Mean)
Nebivolol Treatment3.1

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Change From Baseline in Mean Seated Diastolic Blood Pressure After 6 Weeks of Nebivolol Monotherapy

Office blood pressure measured at trough by automatic oscillometric device. (NCT01057251)
Timeframe: Change from Baseline (Week 0) to Visit 4 (Week 6)

Interventionmm Hg (Mean)
Nebivolol-12.3
Placebo-5.7

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Change From Baseline in Mean Seated Systolic Blood Pressure After 6 Weeks of Nebivolol Monotherapy

Office blood pressure measured at trough by automatic oscillometric device. (NCT01057251)
Timeframe: Change from Baseline Visit 1 (week 0) to Visit 4 (Week 6)

Interventionmm Hg (Mean)
Nebivolol-18.2
Placebo-12.3

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Diastolic Blood Pressure (Millimeter, Mercury) Change From Baseline to Month-12 Between the Groups

Absolute Change in Diastolic Blood Pressure (DBP), (millimeter, Mercury)= Month-12 sitting trough Diastolic Blood Pressure (millimeter, Mercury) level minus baseline sitting trough Diastolic Blood Pressure (millimeter, Mercury). (NCT01157234)
Timeframe: Change in Baseline, Month-12

Interventionmillimeter, mercury (Least Squares Mean)
Nebivolol-0.66
Metoprolol-2.35

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Systolic Blood Pressure (Millimeter, Mercury) Change From Baseline to Month-12 of Treatment Between the Groups

Absolute change in Systolic Blood Pressure (SBP), (millimeter, Mercury)=Month-12 sitting trough SBP level minus baseline sitting trough SBP level (NCT01157234)
Timeframe: Change in Baseline, Month-12

Interventionmillimeter, Mercury (Least Squares Mean)
Nebivolol-2.65
Metoprolol-3.88

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Number of Antihypertensive Drug Classes Change From Baseline to Month-12 Between the Groups.

Percent change in quantity of Anti-Hypertensive Drug Classes (AHDC)=[Month-12 absolute number of AHDC minus baseline absolute number of AHDC] divided by [baseline absolute number of AHDC] multiplied by 100. (NCT01157234)
Timeframe: Change in Baseline, Month-12

Interventionpercent change (Least Squares Mean)
Nebivolol-8.14
Metoprolol8.70

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Percent Change in Plasma Nitric Oxide Level From Baseline to Month-12 of Treatment With Nebivolol in Transplant Recipients < 50 Years Old Compared With Metoprolol in Transplant Recipients < 50 Years Old

(NCT01157234)
Timeframe: Change in Baseline, Month-12

Interventionpercent change (Least Squares Mean)
Nebivolol < 50 Years Old51.55
Metoprolol <50 Years Old-16.64

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Percent Change in Plasma Nitric Oxide Level From Baseline to Month-12 of Treatment With Nebivolol in Transplant Recipients <50 Years Old Compared With Metoprolol in Transplant Recipients >/= 50 Years Old.

(NCT01157234)
Timeframe: Baseline and Month-12

Interventionpercent change (Least Squares Mean)
Nebivolol <50 Year Old51.55
Metoprolol >/= 50 Year Old-17.99

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Percent Change in Plasma Nitric Oxide Level From Baseline to Month-12 of Treatment With Nebivolol in Transplant Recipients >/= 50 Years Old Compared With Metoprolol in Transplant Recipients Age >/= 50 Years Old.

(NCT01157234)
Timeframe: Change in Baseline, Month-12

Interventionpercent change (Least Squares Mean)
Nebivolol >/=50 Years Old-15.25
Metoprolol >/=50 Years Old-17.99

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Percent Change in Plasma Nitric Oxide Level From Baseline to Month-twelve of Treatment With Nebivolol in Transplant Recipients >/= 50 Years Old Compared With Nebivolol in Transplant Recipients < 50 Years Old.

(NCT01157234)
Timeframe: Change in Baseline, Month-12

Interventionpercent change (Least Squares Mean)
Nebivolol >/=50 Years Old-15.25
Metoprolol <50 Years Old-16.64

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Plasma Nitric Oxide Level (Nmol/L) at Month-12 Between the Groups.

(NCT01157234)
Timeframe: 12 Months

Interventionnmol/L (Least Squares Mean)
Nebivolol50.07
Metoprolol38.13

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Plasma Nitric Oxide Level Change From Baseline to Month 12 Between the Groups.

Percent change in Nitric Oxide (NO) blood level (nmol/L)=[Month-12 NO blood level minus baseline NO blood level] divided by [baseline NO blood level] multiplied by 100, where all levels are in nmol/L. (NCT01157234)
Timeframe: Change in Baseline, Month-12

Interventionpercent change (Least Squares Mean)
Nebivolol11.47
Metoprolol-17.27

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Mean Arterial Blood Pressure (Millimeter, Mercury) Change From Baseline to Month-12 Between the Groups

"Absolute change in Mean Arterial Blood Pressure, (MAP), (millimeter, Mercury= Month-12 sitting trough MAP minus baseline sitting trough MAP.~Mean Arterial Pressure= 2/3 trough diastolic blood pressure + 1/3 trough systolic blood pressure" (NCT01157234)
Timeframe: Change in Baseline, Month-12

Interventionmillimeter, Mercury (Least Squares Mean)
Nebivolol-1.07
Metoprolol-3.19

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Estimated Glomerular Filtration Rate (ml/Minute) Change From Baseline to Month-12 Between the Groups

The changed percentage in Estimated Glomerular Filtration Rate (eGFR), (based on the Modification of Diet in Renal Disease Equation)=[Month-12 GFR level minus baseline eGFR level] divided by [baseline eGFR level] multiplied by 100, where all levels are in ml/min. (NCT01157234)
Timeframe: Change in Baseline, Month-12

Interventionpercent change (Least Squares Mean)
Nebivolol2.16
Metoprolol10.43

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Urinary Hydrogen Peroxide Excretion

(NCT01202175)
Timeframe: Baseline (visit 1) and 8 Weeks (visit 2)

,
Interventionumol/ mg Cr (Mean)
Baseline (visit 1)Week 8 (visit 2)
Nebivolol0.6522.79
Placebo0.5000.578

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Urinary Isoprostane Excretion

(NCT01202175)
Timeframe: Basline (visit 1) and 8 weeks (visit 2)

,
Interventionpg/ mg Cr (Mean)
Baseline (visit 1)Week 8 (visit 2)
Nebivolol180213
Placebo165185

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Urinary Nitric Oxide Excretion

(NCT01202175)
Timeframe: Basline (visit 1) and 8 weeks (visit 2)

,
Interventionumol/ mg Cr (Mean)
Baseline (visit 1)Week 8 (visit 2)
Nebivolol40.3164.38
Placebo61.7765.54

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Aortic Augmentation Index for Heart Rate

(NCT01202175)
Timeframe: Basline (visit 1) and 8 weeks (visit 2)

,
Interventionpercentage (Mean)
Baseline (visit 1)Week 8 (visit 2)
Nebivolol14.711.9
Placebo14.512.8

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Aortic Augmentation Pressure

(NCT01202175)
Timeframe: Basline (visit 1) and 8 weeks (visit 2)

,
Interventionmm Hg (Mean)
Baseline (visit 1)Week 8 (visit 2)
Nebivolol7.46.8
Placebo5.55.3

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Aortic Diastolic Blood Pressure (DBP)

(NCT01202175)
Timeframe: Basline (visit 1) and 8 weeks (visit 2)

,
Interventionmm Hg (Mean)
Baseline (visit 1)Week 8 (visit 2)
Nebivolol79.171.3
Placebo75.974

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Aortic Mean Arterial Pressure (MAP)

(NCT01202175)
Timeframe: Basline (visit 1) and 8 weeks (visit 2)

,
Interventionmm Hg (Mean)
Baseline (visit 1)Week 8 (visit 2)
Nebivolol94.286.8
Placebo90.488.6

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Aortic Pulse Pressure

(NCT01202175)
Timeframe: Basline (visit 1) and 8 weeks (visit 2)

,
Interventionmm Hg (Mean)
Baseline (visit 1)Week 8 (visit 2)
Nebivolol33.634.9
Placebo31.832.6

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Aortic Systolic Blood Pressure (SBP)

(NCT01202175)
Timeframe: Basline (visit 1) and 8 weeks (visit 2)

,
Interventionmm Hg (Mean)
Baseline (visit 1)Week 8 (visit 2)
Nebivolol112.7106.2
Placebo107.7106.6

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Heart Rate, Beats Per a Minute

(NCT01202175)
Timeframe: Basline (visit 1) and 8 weeks (visit 2)

,
Interventionbeats per a minute (Mean)
Baseline (visit 1)Week 8 (visit 2)
Nebivolol72.064.4
Placebo75.672.1

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Plasma Interleukin Levels

(NCT01202175)
Timeframe: Basline (visit 1) and 8 weeks (visit 2)

,
Interventionpg/ mL (Mean)
Baseline (visit 1)Week 8 (visit 2)
Nebivolol1.6261.647
Placebo1.3511.351

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Pulse Wave Velocity

(NCT01202175)
Timeframe: Basline (visit 1) and 8 weeks (visit 2)

,
Interventionm/s (Mean)
Baseline (visit 1)Week 8 (visit 2)
Nebivolol6.736.00
Placebo5.955.78

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The Change From Baseline in Trough Seated Systolic Blood Pressure at Week 6.

(NCT01218100)
Timeframe: Visit 6/(Week 0) and Visit 9/(Week 6)

Interventionmm HG (Mean)
Placebo-9.9
Nebivolol + Lisinopril (Combination)-19.2
Nebivolol-14.4
Lisinopril-16.1

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The Change From Baseline in Trough Seated Diastolic Blood Pressure at Week 6.

(NCT01218100)
Timeframe: Visit 6/(Week 0) and Visit 9/(Week 6)

Interventionmm HG (Mean)
Placebo-8.0
Nebivolol + Lisinopril (Combination)-17.2
Nebivolol-13.3
Lisinopril-12.0

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Number of Participants With Reduction of Thin-cap Fibroatheromas (TCFA) as Defined by VH-IVUS

Presence of thin-cap fibroatheroma as defined by virtual histology-intravascular ultrasound (VH-IVUS) (NCT01230892)
Timeframe: 1 year

Interventionparticipants (Number)
Nebivolol4
Atenolol6

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Diastolic Blood Pressure

(NCT01395329)
Timeframe: Diastolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

InterventionmmHg (Mean)
Before Nebivolol89
After Nebivolol77
Before Metoprolol90
After Metoprolol77
Before Placebo86
After Placebo83

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Systolic Blood Pressure

(NCT01395329)
Timeframe: Systolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

InterventionmmHg (Mean)
Before Nebivolol144
After Nebivolol126
Before Metoprolol140
After Metoprolol125
Before Placebo139
After Placebo134

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FBF Response to Acetylcholine (ACh)

FBF was measured via strain-gauge occlusion plethysmography at rest and in response to ACh (4.0, 8.0 and 16.0 ug/100 mL tissue/min) for 5 minutes at each dose. Flows during the last minute of rest and each drug dose were measured and the mean value reported. (NCT01395329)
Timeframe: Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

,,,,,
InterventionmL/100 mL tissue/min (Mean)
BaselineACh 4.0ACh 8.0ACh 16.0
After Metoprolol5.612.013.214.1
After Nebivolol4.913.915.016.4
After Placebo5.113.213.713.9
Before Metoprolol5.312.413.113.8
Before Nebivolol5.212.112.713.3
Before Placebo4.811.412.012.7

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FBF Response to ACh in the Absence or Presence of Nonselective Endothelin A/B Blockade (BQ-123+BQ-788)

FBF was measured via strain-gauge occlusion plethysmography at rest and in response to BQ-123+BQ-788 +ACh (4.0, 8.0 and 16.0 ug/100 mL tissue/min) for 5 minutes at each dose. Flows during the last minute of rest and each drug dose were measured and the mean value reported. (NCT01395329)
Timeframe: Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

,,,,,
InterventionmL/100 mL tissue/min (Mean)
BaselineACh 4.0ACh 8.0ACh 16.0Baseline+BQ123/788ACh 4.0+BQ-123/788ACh 8.0+BQ-123/788ACh 16.0+BQ-123/788
After Metoprolol6.012.413.714.77.416.517.618.2
After Nebivolol4.713.815.016.15.813.714.515.0
After Placebo5.113.313.713.95.615.316.517.3
Before Metoprolol5.513.113.714.56.716.117.117.9
Before Nebivolol5.011.712.312.96.414.615.315.9
Before Placebo4.911.712.313.06.113.515.116.2

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FBF Response to Sodium Nitroprusside

FBF was measured via strain-gauge occlusion plethysmography at rest and in response to sodium nitroprusside (1.0, 2.0 and 4.0 ug/100 mL tissue/min) for 5 minutes at each dose. Flows during the last minute of rest and each drug dose were measured and the mean value reported. (NCT01395329)
Timeframe: Forearm blood flow was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

,,,,,
InterventionmL/100 mL tissue/min (Mean)
BaselineSodium Nitroprusside 1.0Sodium Nitroprusside 2.0Sodium Nitroprusside 4.0
After Metoprolol5.714.315.116.0
After Nebivolol4.713.715.216.4
After Placebo5.213.715.316.1
Before Metoprolol4.914.114.915.8
Before Nebivolol5.213.515.315.9
Before Placebo5.212.814.415.8

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Percent Change in FBF Response to BQ-123 (100 Nmol/Min) + BQ-788 (50 Nmol/Min)

Forearm blood flow (FBF) was measured via strain-gauge venous occlusion plethysmography at rest and every 10 minutes thereafter for 60 minutes. The average percent change for before and after either drug or placebo was calculated as the FBF at (each time point-resting value)/resting value and multiplied by 100 to calculate the percent change. The baseline or resting value was measured before the start of each drug infusion. (NCT01395329)
Timeframe: Forearm blood flow was measured 0-120 minutes before the 12 week drug or placebo intervention and 0-120 minutes after the 12 week drug or placebo intervention.

,,,,,
InterventionPercent change from baseline (Mean)
BQ-123 10 minBQ-123 20 minBQ-123 30 minBQ-123 40 minBQ-123 50 minBQ-123 60 minBQ-123+BQ-788 70 minBQ-123+BQ-788 80 minBQ-123+BQ-788 90 minBQ-123+BQ-788 100 minBQ-123+BQ-788 110 minBQ-123+BQ-788 120 min
After Metoprolol11.118.721.128.927.730.637.832.247.442.048.155.4
After Nebivolol-1.06.0-1.13.86.11.19.216.121.822.318.920.4
After Placebo15.714.723.325.726.530.438.045.047.153.452.849.5
Before Metoprolol10.018.023.028.431.434.433.244.749.847.557.864.6
Before Nebivolol10.217.422.325.625.827.044.041.339.547.447.657.6
Before Placebo13.120.426.823.929.033.837.542.646.457.157.857.9

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Percent Change in Forearm Blood Flow (FBF) Response to BQ-123 (100 Nmol/Min)

Forearm blood flow (FBF) was measured via strain-gauge venous occlusion plethysmography at rest and every 10 minutes thereafter for 60 minutes. The average percent change for before and after either drug or placebo was calculated as the FBF at (each time point-resting value)/resting value and multiplied by 100 to calculate the percent change. The baseline or resting value was measured before the start of each drug infusion. (NCT01395329)
Timeframe: Forearm blood flow was measured at 0-60 minutes before the 12 week drug or placebo intervention and 0-60 minutes after the 12 week drug or placebo intervention.

,,,,,
Interventionpercent change from baseline (Mean)
BQ-123 10 minBQ-123 20 minBQ-123 30 minBQ-123 40 minBQ-123 50 minBQ-123 60 min
After Metoprolol11.118.721.128.927.730.6
After Nebivolol-1.06.0-1.13.86.11.1
After Placebo15.714.723.325.726.530.4
Before Metoprolol10.018.023.028.431.434.4
Before Nebivolol10.217.422.325.625.827.0
Before Placebo13.120.426.823.929.033.8

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Trough Seated Systolic Blood Pressure (SBP)

Change from baseline in mean seated trough cuff Systolic Blood Pressure (SBP) at Week 8 as measured by an Omron device. The secondary efficacy analysis was based on the Intent to Treat (ITT) population using a Last Observation Carried Forward (LOCF) approach. (NCT01415531)
Timeframe: Change from Baseline to Week 8

Interventionmm Hg (Mean)
Placebo-5.5
Nebivolol-13.7

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Trough Seated Diastolic Blood Pressure (DBP)

Change from baseline in mean seated trough cuff Diastolic Blood Pressure (DBP) at Week 8 as measured by an Omron device. The primary efficacy analysis was based on the Intent to Treat (ITT) population using a Last Observation Carried Forward (LOCF) approach. (NCT01415531)
Timeframe: Change from Baseline to Week 8

InterventionmmHG (Mean)
Placebo-5.5
Nebivolol-11.8

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Quality of Life

"Primary outcome measure will be the change from the Screening/Enrollment Visit to the End of the Study/Early Termination visit in scores of four quality of life questionnaires. The four quality of life questionnaires that were used included the following:~Short Form (SF)-36v2 Health Survey (Score Range = 0-100; the lower the score the more disability)~Sexual Dysfunction Tool for Men = International Index of Erectile Function (IIEF) Questionnaire (Score Range = 5-25; a score of 22-25 = No erectile dysfunction; 17-21 = Mild erectile dysfunction; 12-16 = Mild to moderate erectile dysfunction; 8-11 = Moderate erectile dysfunction; 5-7 = Severe erectile dysfunction)~Sexual Dysfunction Tool for Women = Changes in Sexual Functioning Questionnaire (CSFQ-14-F; Score Range = 14-70; a score at or below 42 is indicative of sexual dysfunction)~Multidimensional Assessment of Fatigue (MAF) Scale (Score Range = 1-50; the higher the score the more fatigue)" (NCT01441570)
Timeframe: 12 weeks; Baseline scores were measured at the Initial Screening/Enrollment Visit (Visit 1 - beginning of week 1); Follow-Up scores were measured at the End of the Study (Visit 2 - End of week 12)

,
Interventionunits on a scale (Mean)
Baseline SF-36 (physical) ScoreFollow-Up SF-36 (physical) ScoreChange from Baseline SF-36 (physical)Baseline SF-36 (mental) ScoreFollow-Up SF-36 (mental) ScoreChange from Baseline SF-36 (mental)Baseline MAF ScoreFollow-Up MAF ScoreChange from Baseline MAFBaseline IIEF ScoreFollow-Up IIEF ScoreChange from Baseline IIEFBaseline CSFQFollow-Up CSFQChange from Baseline CSFQ
Metoprolol45.943.6-2.340.342.72.431.717.8-13.91514.3-1.349490
Nebivolol41.146.65.540.6487.427.722.1-5.610.316.36.748.753.04.5

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Blood Pressure

Evaluate the baseline and follow-up systolic and diastolic blood pressures for all subjects in both groups. (NCT01441570)
Timeframe: 12 weeks

,
InterventionmmHg (Mean)
Baseline Systolic Blood PressureFollow-Up Systolic Blood PressureChange from Baseline Systolic Blood PressureBaseline Diastolic Blood PressureFollow-Up Diastolic Blood PressureChange from Baseline Diastolic Blood Pressure
Metoprolol138.8136.0-2.877.073.0-4.0
Nebivolol142.3142.83.673.276.01.6

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Walking Impairment Questionnaire (WIQ) - Change in WIQ Distance Score

Change in distance score as captured by the Walking Impairment Questionnaire (WIQ) distance score subscale. The degree of difficulty in the walking of specific distances is ranked on a 0 to 4 Likert scale, in which 0 represents the inability to walk the distance and 4 represents no difficulty. A Likert scale is an ordinal scale of consecutive, equidistant, numerical values (ie, 0 to 4). The distances assessed in the WIQ range from walking indoors around the home to walking 5 blocks (1500 feet). The items on the subscale are weighted according to the difficulty of walking. The distance score is determined by dividing the total weighted score by the greatest possible weighted score and multiplying by 100. Scores range from 0-100. (NCT01499134)
Timeframe: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.

Interventionunits on a scale (Mean)
Nebivolol13.52
Metoprolol Succinate28.28

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Walking Impairment Questionnaire (WIQ) - Change in Buttock Pain

Change in buttock pain as captured by the Walking Impairment Questionnaire (WIQ). A 5 point Likert scale scoring ranges from 1) No Difficulty, 2) Slight Difficulty, 3) Some Difficulty, 4) Much Difficulty, and 5) Great Difficulty. The scores are determined by dividing the score by the maximum possible score and then multiplying by 100. The score ranges from 0-100 with lower scores indicating greater pain. (NCT01499134)
Timeframe: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.

Interventionunits on a scale (Mean)
Nebivolol-8.3
Metoprolol Succinate14.3

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Peak Walking Time (PWT)

Change in peak walking time (PWT) is measured in seconds. The PWT is defined as when walking on a treadmill cannot continue due to maximal leg pain, resulting in the discontinuation of the treadmill test. (NCT01499134)
Timeframe: Baseline PWT is measured at the time of enrollment and again at the final study visit at 26 weeks.

Interventionseconds (Mean)
Nebivolol110.4
Metoprolol Succinate-19.4

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Claudication Onset Time (COT)

Change in measurement of claudication onset time (COT). The COT is defined as the time when a patient first experienced pain walking during a treadmill test. (NCT01499134)
Timeframe: Baseline COT is measured at the time of enrollment and again at the final study visit at 26 weeks.

Interventionseconds (Mean)
Nebivolol155.7
Metoprolol Succinate148.7

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Ankle-brachial Index (ABI)

Change in measurement of Ankle-brachial index (ABI). The ABI is the ratio of the blood pressure measured in the lower legs to the blood pressure measured in the arms. (NCT01499134)
Timeframe: Baseline ABI is measured at the time of enrollment and again at the final study visit at 26 weeks

InterventionAnkle-Brachial Index (Mean)
Nebivolol0.03
Metoprolol Succinate0.06

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Walking Impairment Questionnaire (WIQ) - Change Calf Pain

Change in calf pain as captured by the Walking Impairment Questionnaire (WIQ). A 5 point Likert scale scoring ranges from 1) No Difficulty, 2) Slight Difficulty, 3) Some Difficulty, 4) Much Difficulty, and 5) Great Difficulty. The scores are determined by dividing the score by the maximum possible score and then multiplying by 100. The score ranges from 0-100 with lower scores indicating greater pain. (NCT01499134)
Timeframe: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.

Interventionunits on a scale (Mean)
Nebivolol25
Metoprolol Succinate10.7

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Walking Impairment Questionnaire (WIQ) - Change in WIQ Speed Score

Change in speed score as captured by the Walking Impairment Questionnaire (WIQ) speed score subscale. In the walking speed component, the degree of difficulty walking is ranked on a 0 to 4 scale where speed is assessed for each of the following speeds: at the following speeds: 1, slowly; 2, average speed; 3, quickly; or 4, running or jogging 1 block. Zero represents the inability to walk the specified speed, and 4 represents no difficulty. The items on the subscale are weighted according to the difficulty of the task. The speed score is determined by dividing the total weighted score by the greatest possible weighted score and multiplying by 100. Scores range from 0-100. (NCT01499134)
Timeframe: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.

Interventionunits on a scale (Mean)
Nebivolol21.88
Metoprolol Succinate-6.83

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Walking Impairment Questionnaire (WIQ) - Change in WIQ Stairs Score

Change in stairs score as captured by the Walking Impairment Questionnaire (WIQ) stairs subscale. This scale item asks the subject to describe the degree of difficulty climbing one, two, or three flights of stairs in the past week. A flight of stairs is defined as 14 steps. A 5 point Likert scale scoring ranges from 1) No Difficulty, 2) Slight Difficulty, 3) Some Difficulty, 4) Much Difficulty, 5) Unable to Do, or 6) Didn Do for Other Reasons. The items on the subscale are weighted according to the difficulty of the task. The stairs score is determined by dividing the total weighted score by the greatest possible weighted score and multiplying by 100. Scores range from 0-100. (NCT01499134)
Timeframe: Baseline WIQ is completed at the time of enrollment and again at the final study visit at 26 weeks.

Interventionunits on a scale (Mean)
Nebivolol21.67
Metoprolol Succinate24.31

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Endothelial Cell Protein Expression p47phox From Endothelial Cell Collection

Endothelial cell (EC) was collected after a 20-guage angiocatheter was inserted into the contralateral forearm vein under sterile conditions. Three J-shaped vascular guidewires (St. Jude, St. Paul, MN) were advanced sequentially into the vein up to 10 cm. Endothelial cells were collected by gentle abrasion and placed into a dissociation buffer (0.5% bovine serum albumin, 2mM EDTA, and 100 ug/ml heparin in PBS). Endothelial cells were recovered from the tips of guide wires by repeated washing into collection tubes and subsequent centrifugation. EC were incubated with monoclonal antibodies against the polyclonal antibodies against NADPH oxidase p47 subunit. The intensity of staining was measured using fluorescence microscopy. (NCT01501929)
Timeframe: 12 weeks

InterventionRatio human to HUVEC p47Phox expression (Mean)
Metoprolol0.47
Nebivolol0.44

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Microvascular Blood Flow

Microvascular perfusion of skeletal muscle were measured during handgrip at 20 cycle per minute after 12 weeks of metoprolol, and after 12 weeks of nebivolol (NCT01501929)
Timeframe: 12 weeks

Interventionvideo intensity units/ second (Median)
Metoprolol43.938
Nebivolol74.584

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Blood Pressure During Angiotensin II Infusion

(NCT01502787)
Timeframe: 12 weeks after initiation of metoprolol

InterventionmmHg (Mean)
Metoprolol114
Nebivolol113

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Blood Pressure During Exercise

(NCT01502787)
Timeframe: 12 weeks

InterventionmmHg (Mean)
Initial Treatment With Metoprolol101
Initial Treatment With Nebivolol103

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Forearm Blood Flow

(NCT01502787)
Timeframe: 12 weeks after each specified medication

Interventionml/min (Mean)
First Intervention Metoprolol: 12 Weeks96
Second Intervention Nebivolol: 24 Weeks105

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Change in Diastolic Blood Pressure

Change in diastolic blood pressure as measured by sphygmomanometer from baseline to 9 months after intervention initiation. (NCT01522950)
Timeframe: baseline, 9 months

InterventionmmHg (Mean)
Nebivolol-8.5
Atenolol-8.5
Placebo-2.9

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Change in Large Artery Elasticity

Change in large artery elasticity (a marker for endothelial function) from baseline to 9 months after intervention initiation. (NCT01522950)
Timeframe: baseline, 9 months

Intervention(ml/mmHg × 10) (Mean)
Nebivolol3.2
Atenolol2.9
Placebo0.2

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Change in Small Artery Elasticity

Change in small artery elasticity (a marker for endothelial function) from baseline to 9 months after intervention initiation. (NCT01522950)
Timeframe: baseline, 9 months

Intervention(ml/mmHg × 100) (Mean)
Nebivolol2.4
Atenolol1.0
Placebo0.4

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Change in Systolic Blood Pressure

Change in systolic blood pressure as measured by sphygmomanometer from baseline to 9 months after intervention initiation. (NCT01522950)
Timeframe: baseline, 9 months

InterventionmmHg (Mean)
Nebivolol-9
Atenolol-13
Placebo-3.2

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Diastolic Blood Pressure

(NCT01595516)
Timeframe: Diastolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

,,
InterventionmmHg (Mean)
Before InterventionAfter Intervention
Metoprolol8779
Nebivolol8578
Placebo8581

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Endothelial t-PA Release in Response to Bradykinin (BDK) and Bradykinin+Vitamin C (BDK+C) Before and After 12 Weeks of Nebivolol Therapy.

Net endothelial release of t-PA antigen in response to bradykinin (BDK) and bradykinin+vitamin C (BDK+C) was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x [101-hematocrit/100]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK) and BDK+Vit C. t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells. (NCT01595516)
Timeframe: t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention.

,,,
Interventionng/100 mL tissue/min (Mean)
Amount of t-PA release to salineAmount of t-PA release to BDK 12.5Amount of t-PA release to BDK 25.0Amount of t-PA release to BDK 50.0
After Nebivolol: Saline-1.528.249.167.5
After Nebivolol: Vitamin C-3.838.154.279.9
Before Nebivolol: Saline-2.414.327.647.2
Before Nebivolol: Vitamin C-1.431.352.780.5

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Endothelial t-PA Release in Response to Bradykinin (BDK) Before and After the 12 Week Intervention

Net endothelial release of t-PA antigen in response to bradykinin (BDK) was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x [101-hematocrit/100]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK). t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells. (NCT01595516)
Timeframe: t-PA release was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

,,,,,
Interventionng/100 mL tissue/min (Mean)
Amount of t-PA release to SalineAmount of t-PA release to BDK 12.5Amount of t-PA release to BDK 25.0Amount of t-PA release to BDK 50.0
After Metoprolol-1.916.631.252.7
After Nebivolol-1.825.246.472.8
After Placebo-0.917.632.752.9
Before Metoprolol-1.214.427.548.2
Before Nebivolol-1.215.729.147.2
Before Placebo-0.218.128.351.1

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Heart Rate

Resting heart rate in the seated position (NCT01595516)
Timeframe: Heart rate was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

,,
Interventionbpm (Mean)
Before InterventionAfter Intervention
Metoprolol7164
Nebivolol6458
Placebo6972

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Systolic Blood Pressure

(NCT01595516)
Timeframe: Systolic blood pressure was measured before the 12 week drug or placebo intervention and after the 12 week drug or placebo intervention.

,,
InterventionmmHg (Mean)
Before InterventionAfter Intervention
Metoprolol138125
Nebivolol140125
Placebo138135

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Endothelial t-PA Release in Response to BDK and BDK+C Before and After 12 Weeks of Metoprolol Therapy.

Net endothelial release of t-PA antigen in response to BDK and BDK+C was calculated using the following equation: Net Release of t-PA Antigen=(Cv-Ca) x (FBF x [101-hematocrit/100]) where Cv and Ca represent the concentration of t-PA in the vein and artery respectively. A positive difference indicates a net release and a negative difference net uptake. Arterial and venous blood samples are collected simultaneously at baseline and each dose of the drug (BDK) and BDK+Vit C. t-PA concentration were determined by enzyme immunoassay. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the trapped red blood cells. (NCT01595516)
Timeframe: t-PA release was measured before the 12 week drug intervention and after the 12 week drug intervention.

,,,
Interventionng/100 mL tissue/min (Mean)
Amount of t-PA release to SalineAmount of t-PA release to BDK 12.5Amount of t-PA release to BDK 25.0Amount of t-PA release to BDK 50.0
After Metoprolol: Saline-1.316.431.349.9
After Metoprolol: Vitamin C-2.730.046.473.8
Before Metoprolol: Saline-2.710.124.545.0
Before Metoprolol: Vitamin C-2.531.147.182.4

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Exercise Duration

Assessment of exercise duration as determined by CPET (NCT01665508)
Timeframe: 3 months

Interventionminutes (Mean)
Nebivolol11.9
Baseline11.8

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Peak Heart Rate as Measured by Cardiopulmonary Exercise Testing

Assessment of peak heart rate as determined by CPET (NCT01665508)
Timeframe: 3 months

Interventionbeats per minute (Mean)
Nebivolol119
Baseline145

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Peak O2 Pulse

peak O2 pulse as measured by cardiopulmonary exercise testing (NCT01665508)
Timeframe: 3 months

Interventionml/beat (Mean)
Nebivolol13.1
Baseline11

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Peak VO2 Measured by Cardiopulmonary Exercise Testing

Assessment of exercise capacity (peak VO2) as determined by CPET (NCT01665508)
Timeframe: 3 months

Interventionml/beat (Mean)
Nebivolol13.1
Baseline11.0

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Seattle Angina Questionnaire Score

"Seattle Angina Questionnaire (SAQ):~The SAQ is a 5 part survey that is widely used and well validated tool to assess angina stability and angina frequency among patients with coronary artery disease.~The SAQ is a validated, self-administered 19-item questionnaire with 5 different dimensions of health status in patients with CAD including: angina frequency, angina stability, disease-specific quality of life, physical limitations and treatment satisfaction. Each SAQ domain score ranges from 0-100, with higher scores indicating a better health status." (NCT01665508)
Timeframe: 3 months

,
Interventionunits on a scale (Mean)
anginal stabilityphyisical limitationanginal frequencytreatment satisfactionqualify of life
Baseline29.267.670.084.451.4
Nebivolol83.374.180.081.362.5

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SF36

The SF-36v2 is a commonly used instrument to assess HRQoL8. The questionnaire evaluates 8 HRQoL domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role emotional and mental health. The physical component score is a composite of the SF-36v2 physical health domains (physical functioning, role-physical, bodily pain and general health) and the mental component score a composite of the mental health domains (vitality, social functioning, role-emotional and mental health). Each HRQoL domain score ranges from 0 to 100, with higher scores corresponding to a better health status. The SF-36v2 domain scores were calculated using the QualityMetric Health Outcomes Scoring Software version 4.5. (NCT01665508)
Timeframe: baseline and 12 week follow-up

,
Interventionunits on a scale (Mean)
physical functioningrole-physicalbodily paingeneral healthvitalitysocial functioningrole-emotionalmental healthphysical componentmental component
Baseline67.982.378.772.863.591.797.281.748.456.7
Nebivolol75.085.475.27567.791.790.381.750.355.3

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Insulin Sensitivity (HOMA-IR)

The HOMA index was calculated as the product of plasma blood glucose and insulin divided by 22.5. (NCT01920282)
Timeframe: 12 weeks

InterventionArbitrary units (Mean)
Nebivolol-0.36
Lifestyle Modification-1.98
Nebivolol Plus Lifestyle Modification-2.12

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Beta-stiffness Index

Longitudinal B-mode images of the left common carotid artery diameter (1-2 cm proximal to the carotid bulb) were obtained over 15 consecutive cardiac cycles. Brachial blood pressure was measured via an automated sphygmomanometer. Quantification of systolic and diastolic carotid artery diameters were analyzed with the Vascular Research Tools 5 software program. Beta-stiffness index was calculated as: Beta = ln(P1/P0)/((D1-D0)/D0), where D0 represents the minimal diameter recorded during diastole, D1 represents the maximal diameter recorded during systole, P0 represents the pressure measured during diastole, and P1 represents the pressure measured during systole. (NCT01920282)
Timeframe: 12 weeks

InterventionArbitrary units (Mean)
Nebivolol-2.03
Lifestyle Modification-1.87
Nebivolol Plus Lifestyle Modification-2.51

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Untwist Rate of the Left Ventricle

measured as a part of stress echocardiogram, number of participants with significant improvement in the LV untwist after Nebivolol treatment in patients who completed the study (NCT01961323)
Timeframe: at 6 months

InterventionParticipants (Count of Participants)
Nebivolol0

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E Velocity Indexed to e' (E/e' Ratio) of the Left Ventricle

measured as a part of stress echocardiogram, E/e' ratio: The normal E/e' ratio from the medial annulus is <8 and suggests a normal left atrial pressure. While values between 8 and 12 are indeterminate, a value >12 is indicative of an elevated left atrial pressure or PCWP (>18mmHg). The ranges for E/e' from the lateral mitral annulus are <5, 5 -10 and >10 respectively. (NCT01961323)
Timeframe: at 6 months

Interventionratio (Mean)
RestingPeak Exercise
Nebivolol7.58.8

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Improvement in Exercise Tolerance

measured by stress echocardiogram, number of participants who had improvement in METS and improvement in exercise time as compared to their baseline. (NCT01961323)
Timeframe: at 6 months

InterventionParticipants (Count of Participants)
Improvement in METs and exercise timeImprovement in exercise time only
Nebivolol98

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Changes in Pulmonary Vascular Pressure

Difference between baseline and 18 week mean pulmonary artery pressure and pulmonary artery wedge pressure (NCT02053246)
Timeframe: baseline - 18 weeks

InterventionmmHg (Mean)
Mean Pulmonary Artery Pressure ChangePulmonary Artery Wedge Pressure Change
Nebivolol0.431.0

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Changes in 6-minute Walk Distance

Difference in 6-minute walk distance between baseline and 18 weeks. (NCT02053246)
Timeframe: baseline - 18 weeks

Interventionfeet (Mean)
Nebivolol-44.0

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24-h, Wake and Sleep Period Systolic and Diastolic Blood Pressure

"24-h Systolic Blood Pressure is the average of all 24-h Ambulatory Systolic Blood Pressure recordings. The Wake Period Systolic Blood Pressure is the average of all Systolic Blood Pressures recorded every 15 minutes during the wake period. The Sleep Period Systolic Blood pressure is the average of all Systolic Blood Pressures recorded every 30 minutes during the sleep period.~24-h Diastolic Blood Pressure is the average of all 24-h Ambulatory Diastolic Blood Pressure recordings. The Wake Period Diastolic Blood Pressure is the average of all Diastolic Blood Pressures recorded every 15 minutes during the wake period. The Sleep Period Diastolic Blood pressure is the average of all Diastolic Blood Pressures recorded every 30 minutes during the sleep period." (NCT02710071)
Timeframe: At the end of 2 weeks of placebo therapy, at the end of 6 weeks of Nebivolol therapy and at the end of 6 weeks of hydrochlorothiazide therapy.

,,
InterventionmmHg (Mean)
24-h systolic blood pressure24-h diastolic blood pressureWake systolic blood pressureWake diastolic blood pressureSleep systolic blood pressureSleep diastolic blood pressure
Hydrochlorothiazide133801388512775
Nebivolol130771358112371
Placebo137821418612976

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Change in Patient-reported Quality of Life When on Beta-blocker Versus When Off Beta-blocker, as Measured by Patient-Reported Outcome Measurement Information System-29 (PROMIS-29)

"The PROMIS-29 assesses 7 domains with 4 questions with an additional pain intensity numeric rating scale. The patients' answers to the PROMIS-29 are scored from 1-5 (except for the pain numeric rating scale). The sum of the PROMIS-29 is the raw score transformed into a final T-score metric. Scores are mapped so that the values follow a normal distribution with a population mean T-score of 50 and an SD of 10. Instead of having a min or max, the PROMIS-29 raw scores have been transformed into t-scores for comparison to a reference population (the US general population) with a mean of 50 and SD of 10. Scores lower than 50 indicate worse health compared to the US general population. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's home dose of beta-blocker before enrollment, therefore, each subject's respective period for the OFF and ON periods could range between 3 - 6 weeks. The values measured over the time points were averaged." (NCT04767061)
Timeframe: The maximum amount of time a subject could have been assessed for this measure is 76-weeks (24-week max intervention phase,1-year follow-up phase). This outcome was measured at baseline, weekly, end of period and intervention visits, and during follow-up.

,
Interventionscore on a scale (Mean)
Physical Health ComponentMental Health Component
OFF Beta Blockers40.047.9
ON Beta Blockers39.846.8

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Change in Patient-reported Sexual Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by Patient-Reported Outcome Measurement Information System-Sexual Function (PROMIS-Sexual Function)

"Patient-Reported Outcome Measurement Information System-Sexual Function (PROMIS-Sexual Function) measures self-reported sexual function and satisfaction. Questions are ranked on a 6-point Likert scale, with higher scores indicating poorer sexual function and satisfaction. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's home dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the span of the outcome measure time frame. The score ranges from 0-10 with higher scores meaning worsened sexual function." (NCT04767061)
Timeframe: The maximum amount of time a subject could have been assessed for this measure is 76-weeks (24-week max intervention phase,1-year follow-up phase). This outcome was measured at baseline, end of period and intervention visits, and during follow-up.

Interventionscore on a scale (Mean)
ON Beta Blockers1.8
OFF Beta Blockers2.1

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Change in Patient-reported Health Status When on Beta-blocker Versus When Off Beta-blocker, as Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ-12)

"The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a heart failure-specific health status survey. Questions are ranked on 5- to 7-point Likert scales, with higher scores indicating better health status. KCCQ scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's home dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the span of the outcome measure time frame." (NCT04767061)
Timeframe: The max amount of time a subject could have been assessed for this measure is 76-weeks (24-week max intervention phase,1-year follow-up phase). This outcome was measured at baseline, bi-weekly, end of period and intervention visits, and during follow-up.

Interventionscore on a scale (Mean)
ON Beta Blockers58.7
OFF Beta Blockers66.0

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Change in Patient-reported Health When on Beta-blocker Versus When Off Beta-blocker, as Measured by the EuroQol-5D Visual Analogue System (EQ-5D VAS)

"The EuroQol-5D Visual Analogue System (EQ-5D VAS) indicates patient-perceived health on a vertical visual analogue scale. The scale ranges from 0, indicating poorest health, to 100, indicating the best health. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's home dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the span of the outcome measure time frame." (NCT04767061)
Timeframe: The maximum amount of time a subject could have been assessed for this outcome measure is 24-weeks. This outcome was measured at baseline and at each end of period visit.

Interventionscore on a scale (Mean)
ON Beta Blockers68.9
OFF Beta Blockers67.8

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Change in Patient-reported Cognitive Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by Patient-Reported Outcome Measurement Information System-Short Form 6a (PROMIS SF-6a)

"Patient-Reported Outcome Measurement Information System-Short Form 6a (PROMIS SF-6a) is a survey of patient-perceived cognitive deficits. Questions are ranked on a 5-point Likert scale, with higher scores indicating better cognitive function. Scores are mapped so the values follow a normal distribution with a population mean T-score of 50 and an SD of 10. Instead of having a min or max, the raw scores have been transformed into t-scores for comparison to a reference population (the US general population) with a mean of 50 and SD of 10. Scores lower than 50 indicate worse cognitive function compared to the US general population. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's home dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3-6 weeks. The outcome measure data is the mean of the data collected during the span of the measured time points." (NCT04767061)
Timeframe: The maximum amount of time a subject could have been assessed for this measure is 76-weeks (24-week max intervention phase,1-year follow-up phase). This outcome was measured at baseline, weekly, end of period and intervention visits, and during follow-up.

Interventionscore on a scale (Mean)
ON Beta Blockers53.8
OFF Beta Blockers52.4

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Change in Physical Activity When on Beta-blocker Versus When Off Beta-blocker, as Measured by Step Count on Wearable Activity Monitoring Device

"The wearable activity monitoring device measures daily step count. Due to the nature of N-of-1 trials, the duration of a subject's periods varies based on the subject's home dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 and 6 weeks. We will compare average step counts over 2-week periods, which will be the final 2 weeks of each period when subjects are either on their home (ON Beta Blockers) or minimally tolerated (OFF Beta Blockers) dose. The outcome measure data is the mean collected during the outcome measure time frame." (NCT04767061)
Timeframe: The maximum amount of time a subject could have been assessed for this outcome measure is 8-weeks (last 2 weeks of each period for up to 4 periods).

InterventionCount of Steps (Mean)
ON Beta Blockers2790.5
OFF Beta Blockers3167.3

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Change in Exercise Capacity When on Beta-blocker Versus When Off Beta-blocker, as Measured by Peak Oxygen Consumption (VO2) During Cardiopulmonary Exercise Test (CPET)

"Cardiopulmonary exercise testing (CPET) measures breath-by-breath oxygen production during symptom-limited exercise on a stationary bike. This permits the calculation of peak oxygen consumption (VO2). Percent predicted peak VO2 for body weight will also be calculated. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's home dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the span of the outcome measure time frame." (NCT04767061)
Timeframe: The maximum amount of time a subject could have been assessed for this outcome measure is 6-weeks. This outcome was measured at the end of the first and second visit.

Interventionml/kg/min (Mean)
ON Beta Blockers10.0
OFF Beta Blockers11.4

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Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Balance Portion of a Modified Version of the Short Physical Performance Battery.

"The Short Physical Performance Battery assesses gait speed, core strength when rising from a chair without using the upper extremities, and balance while standing without a cane or walker. The balance test portion of the SPPB assesses the subject's ability to stand unassisted without the use of a cane or walker. Balance test scores range from 0 - 4 with higher scores indicating better ability to stand unassisted. Our research team conducted the balance test according to SPPB standards. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's home dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the span of the outcome measure time frame." (NCT04767061)
Timeframe: The maximum amount of time a subject could have been assessed for this outcome measure is 24-weeks. This outcome was measured at baseline and at each end of period visit.

Interventionscore on a scale (Mean)
ON Beta Blockers3.9
OFF Beta Blockers3.6

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Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Gait Speed Portion of a Modified Version of the Short Physical Performance Battery.

"The Short Physical Performance Battery assesses gait speed, core strength when rising from a chair without using the upper extremities, and balance while standing without a cane or walker. The gait speed portion of the SPPB assesses the subject's lower extremity function. When comparing the number of seconds it takes to complete the 4-meter gait speed test, quicker speeds indicate better lower extremity function. Our research team conducted the 4-meter gait speed test according to SPPB standards, but have chosen on comparing the speed at which subjects were able to complete the test. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's home dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the span of the outcome measure time frame." (NCT04767061)
Timeframe: The maximum amount of time a subject could have been assessed for this outcome measure is 24-weeks. This outcome was measured at baseline and at each end of period visit.

Interventionseconds (Mean)
ON Beta Blockers4.3
OFF Beta Blockers4.6

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Change in Lower Extremity Function When on Beta-blocker Versus When Off Beta-blocker, as Measured by the Chair Rise Portion of a Modified Version of the Short Physical Performance Battery.

"The Short Physical Performance Battery assesses gait speed, core strength when rising from a chair without using the upper extremities, and balance while standing without a cane or walker. The chair rise portion of the SPPB assesses core strength. When comparing the number of seconds it takes to complete 5 chair rises, quicker speeds indicate better core strength. Our research team has chosen on comparing the speed at which subjects were able to complete the test. Due to the nature of N-of-1 trials, the duration of a subject's period varies based on the subject's home dose of beta-blocker prior to enrollment, therefore, each subject's respective time period for the OFF and ON periods could range between 3 - 6 weeks. The outcome measure data is the mean of the data collected during the outcome measure time frame." (NCT04767061)
Timeframe: The maximum amount of time a subject could have been assessed for this outcome measure is 24-weeks. This outcome was measured at baseline and at each end of period visit.

Interventionseconds (Mean)
ON Beta Blockers16
OFF Beta Blockers15.1

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