Tolerability Of Nebivolol Research Articles

The Safety and Tolerability of Nebivolol in Hypertensive Patients with Coronary Artery Disease and Left Ventricular Ejection Fraction ≥ 40%: A Population-Based Cohort Study (Nebivolol-TR Study).

This study aimed to assess the safety and tolerability of nebivolol in hypertensive patients with coronary artery disease and left ventricular ejection fraction ≥ 40% in a Turkish cohort. A total of 1015 hypertensive patients and coronary artery disease with left ventricular ejection fraction ≥ 40% were analyzed from 29 different centers in Turkey. Primary outcomes were the mean change in blood pressure and heart rate. Secondary outcomes were to assess the rate of reaching targeted blood pressure (<130/80 mmHg) and heart rate (<60 bpm) and the changes in the clinical symptoms (angina and dyspnea). Adverse clinical events and clinical outcomes including cardiovascular mortality, cardiovascular hospital admissions, or acute cardiac event were recorded. The mean age of the study population was 60.3 ± 11.5 years (male: 54.2%). During a mean follow-up of 6 months, the mean change in blood pressure was -11.2 ± 23.5/-5.1 ± 13.5 mmHg, and the resting heart rate was -12.1 ± 3.5 bpm. Target blood pressure and heart rate were achieved in 76.5% and 37.7% of patients. Angina and functional classifications were improved by at least 1 or more categories in 31% and 23.2% of patients. No serious adverse events related to nebivolol were reported. The most common cardiovascular side effect was symptomatic hypotension (4.2%). The discontinuation rate was 1.7%. Cardiovascular hospital admission rate was 5% and hospitalization due to heart failure was 1.9% during 6 months' follow-up. Cardiovascular mortality rate was 0.1%. Nebivolol was well tolerated and safe for achieving blood pressure and heart rate control in hypertensive patients with coronary artery disease and heart failure with preserved or mildly reduced ejection fraction.

Efficacy and safety of nebivolol in hypertensive patients: a meta-analysis of randomized controlled trials.

PurposeOur meta-analysis was undertaken to evaluate the efficacy and safety of nebivolol compared with other second-generation β blockers for hypertensive patients.MethodsWe searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov databases for randomized controlled trials (RCTs). The efficacy endpoints included systolic blood pressure (SBP), diastolic blood pressure (DBP), reduction of SBP and DBP, heart rate (HR), and adverse events (AEs).FindingsEight RCTs with 1514 patients met the inclusion criteria. HR was significantly lower in patients receiving other second-generation β blockers compared with patients receiving nebivolol. There was no difference the reduction of blood pressure (SBP and DBP) or the reduction of SBP or DBP between the groups. The incidence of AEs was lower in patients taking nebivolol compared with patients taking other second-generation β blockers.ConclusionsNo significant difference was demonstrated between nebivolol and other second-generation β blockers in the reduction of blood pressure, SBP, and DBP. The tolerability of nebivolol was significantly better compared with other second-generation β blockers, and nebivolol was also associated with a stable HR and a lower risk of AEs compared with other second-generation β blockers.

Efficacy and tolerability of nebivolol added to RAAS inhibitors

entered a 21 day single blind placebo washout period. Thirty hour ABPMs were performed on all patients and qualifying patients were randomized to Valsartan ER 160mg QD or to Diovan 160mg QD for a 21 day treatment period. After 21 days of active treatment all patients had a repeat 30 hour ABPM and then entered into a second 21 day single blind placebo washout period. Patients were then switched to the alternative treatment for a second 21 day active treatment period following which a third 30 hour ABPM was performed. On day 1 and day 21 of each active treatment period, all patients were admitted to the PK unit and PK samples were drawn to establish the pharmacokinetic profile of each of the drugs. A comparison of mean 24 hour, mean daytime and mean nighttime BP as measured by ABPM was performed on patients treated with Valsartan ER versus those treated on Diovan. In addition, a comparison of BP reductions during the final 4 hours of the dosing interval was performed. Mean BP measured 28 to 30 hours post dose was also compared in the patients treated with either Valsartan ER or Diovan after patients had missed a treatment dose.

NEBIVOLOL A NOVEL SOMEWHAT DIFFERENT ΒETA ADRENERGIC RECEPTOR BLOCKER

Nebivolol is a highly selective β1 adrenoceptor blocker available clinically and is devoid of intrinsic sympathomimetic activity, inverse agonistic activity, and α1 receptor blocking properties along with peripheral vasodilatation and nitric oxide (NO) induced benefits such as antioxidant activity and reversal of endothelial dysfunction. Nebivolol is the racemic mixture of 2 isomers with 4 asymmetric centres. The d-isomer is the active b-blocking component, while the l-isomer is responsible for the release of nitric oxide. Nebivolol has a hemodynamic profile different from classic β receptor antagonists that iit acutely lowers arterial blood pressure without depressing left ventricular function, and reduces systemic vascular resistance. Nebivolol shown to inhibit platelet aggregation and thrombus formation, it has also an antiproliferative effects and reverses endothelial dysfunction in animal models of oxidative stress. Clinically, this compound has been proven to have antihypertensive and anti-ischemic effects as well as beneficial effects on hemodynamics. The tolerability of nebivolol has been shown to be superior to that of other beta blocker. Further studies are now necessary to compare the benefit of nebivolol with that of other drugs in the same class and to prove its claims of superiority and novelty of action, most importantly, its prognostic impact in patients with hypertension and its potential benefit in other comorbid conditions. Keywords- Nebivolol, β1 adrenoceptor blocker. Â

Efficacy and tolerability of nebivolol: does age matter? A retrospective analysis of three randomized, placebo-controlled trials in stage I–II hypertension

This retrospective analysis examined the efficacy and tolerability of nebivolol, a ß(1)-selective, vasodilatory β-blocker, in four different age groups of patients with hypertension. Data were pooled from three 12-week, randomized, placebo-controlled trials (placebo, n = 205; nebivolol [1.25-30/40 mg/day], n = 1811) and stratified into age quartiles (Group 1: 22-46 years; Group 2: 47-53 years; Group 3: 54-62 years; Group 4: 63-84 years). Only patients treated with placebo and the three commonly used nebivolol dosages (5, 10, and 20 mg/day) are presented. Baseline-to-endpoint changes in trough sitting diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR) were analyzed for each age quartile using an analysis of covariance (ANCOVA) model. Tolerability was assessed by means of adverse event (AE) rates. The analysis comprised 205 placebo-treated patients and 1380 patients treated with nebivolol dosages of 5, 10, or 20 mg/day. Older age was associated with higher SBP values at baseline. In all age groups, each of the three most frequently used nebivolol dosages significantly reduced DBP, compared with placebo (-9.1 to -11.8 mmHg versus -3.4 to -5.9 mmHg; p ≤ 0.008 overall). For SBP, a statistically significant effect versus placebo was observed for all dosages and age groups except for 5 and 10 mg/day in Group 4. Within each group, treatment with nebivolol (all three dosages) and placebo resulted in similar AE rates (nebivolol: 26.1-36.6%; placebo: 36.2-42.6%) and AE-related discontinuation rates (1.8-3.8% versus 0-4.3%). In each age group, there were no significant nebivolol-placebo differences in the rates of patients who experienced clinically significant changes or abnormal endpoint levels of metabolic parameters. This retrospective analysis suggests that nebivolol monotherapy is efficacious and well tolerated across various age groups, with the efficacy in reducing SBP somewhat diminishing in patients over 62 years of age.

Efficacy and Tolerability of Nebivolol in Stage I–II Hypertension: A Pooled Analysis of Data From Three Randomized, Placebo-Controlled Monotherapy Trials

Background Nebivolol is a β 1-selective β-blocker with NO-mediated vasodilatory properties, approved in the United States for the treatment of stage I–II hypertension. Objective The purpose of this pooled analysis was to summarize efficacy and provide a brief overview of the tolerability associated with the use of nebivolol. Methods PubMed was searched for randomized, double-blind, placebo-controlled, parallel-group trials of monotherapy with nebivolol for stage I–II hypertension of at least 12 weeks' duration. This article reports pooled changes in sitting diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR) at trough; proportions of responders (patients whose end-point sitting DBP at trough was <90 mm Hg or whose sitting DBP at trough had decreased from baseline by ≤10 mm Hg); and the most frequent adverse events (AEs). These data were also summarized in the subpopulation of black patients. Results The literature search yielded 3 similarly designed studies. In all 3 trials, a single-blind placebo run-in phase (4–6 weeks) was followed by randomization (baseline) and a 12-week double-blind treatment phase in which patients received nebivolol 1.25 to 30 or 40 mg/d or placebo. The primary efficacy measure in all 3 trials was the mean change from baseline in sitting DBP at 12 weeks, based on the intent-to-treat population. In the pooled sample, 930 (46.1%) patients were women, and the mean age was 53.6 years. Compared with placebo (n = 205), the reductions in DBP (up to 11.1 mm Hg), SBP (up to 12.4 mm Hg), and HR (up to 9.2 beats/min) were significantly greater with nebivolol (n = 1811) at the recommended dosages of 5–30/40 mg/d (all, P < 0.001). The most commonly reported AEs were headache (nebivolol, all dosages, 7.1%; placebo, 5.9%), fatigue (3.6% vs 1.5%, respectively), and nasopharyngitis (3.1% vs 4.4%). The efficacy and tolerability of nebivolol in black patients were similar to those observed in the total study population. Conclusion Based on the pooled results from the 3 monotherapy trials reported here, nebivolol administered for 12 weeks was efficacious and generally well tolerated in patients with stage I–II hypertension.

β-Blockers in Patients With Intermittent Claudication and Arterial Hypertension

The use of β-receptor blockers in peripheral arterial disease is controversial for their impact on vasomotor tone. The β-blocker nebivolol possesses vasodilating, endothelium-dependent, NO-releasing properties that might be beneficial in peripheral arterial disease. The aim of the study was to evaluate the effects and tolerability of nebivolol in comparison with metoprolol in these patients. A total of 128 patients with intermittent claudication and essential hypertension were included and double-blind randomized to receive 5 mg of nebivolol (N=65) or 95 mg of metoprolol (N=63) once daily. End points were changes in ankle-brachial index, initial and absolute claudication distance, endothelial function assessed by flow-mediated dilatation of the brachial artery, blood pressure, and quality of life using the claudication scale questionnaire. End point analysis was possible in 109 patients (85.2%). After the 48-week treatment period, ankle-brachial index and absolute claudication distance improved significantly in both patient groups (P<0.05 for both), with no difference across treatments. A significant increase of initial claudication distance was found in the nebivolol group. Adjusted mean change of initial claudication distance was 33.9% after nebivolol (P=0.003) and 16.6% after metoprolol (P=0.12) treatment. Quality of life was not influenced by either treatment, and there was no relevant change in flow-mediated dilatation in patients treated with nebivolol or metoprolol (P=0.16). Both drugs were equally effective in lowering blood pressure. In conclusion, β-blocker therapy was well tolerated in patients with intermittent claudication and arterial hypertension during a treatment period of ≈1 year. In the direct comparison, there was no significant difference between nebivolol and metoprolol.

The Efficacy and Tolerability of Nebivolol in Hypertensive African American Patients

Hypertensive African Americans often respond poorly to beta-blocker monotherapy, compared with whites. There is evidence, however, that suggests that this response may be different if beta-blockers with vasodilating effects are used. This 12-week, multi-center, double-blind, randomized placebo-controlled study assessed the antihypertensive efficacy and safety of nebivolol, a cardioselective, vasodilating beta1-blocker, at doses of 2.5, 5, 10, 20, or 40 mg once daily in 300 African American patients with stage I or II hypertension (mean sitting diastolic blood pressure [SiDBP] > or =95 mm Hg and < or =109 mm Hg). The primary efficacy end point was the baseline-adjusted change in trough mean SiDBP. After 12 weeks, nebivolol significantly reduced least squares mean SiDBP (P< or =.004) at all doses of 5 mg and higher and sitting systolic blood pressure (P< or =.044) at all doses 10 mg and higher, compared with placebo. The drug was safe and well-tolerated, with no significant difference in the incidence of adverse events compared with placebo. Nebivolol monotherapy provides antihypertensive efficacy, with few significant adverse effects, in hypertensive African Americans.

Nebivolol: More Than a Highly Selective Beta Blocker

Although their specific mechanisms of action are incompletely understood, beta blockers are most likely lower blood pressure and provide target organ protection by several different mechanisms, including inhibition of renin-angiotensine system by decreasing renin release by the jugstaglomerular cells of the kidney, central inhibition of sympathetic nervous system outflow and slowing of heart rate with a decrease in cardiac output. These agents are widely recommended as important parts of antihypertensive regimens and as well as preferred therapies for patients at high risks of coronary heart disease, and including those with angina pectoris, myocardial infarction or heart failure. The third generation beta blockers are distinguished from the earlier class of beta blockers by their vasodilating activity. Labetalol, carvedilol and bucindolol appear to provide a vasodilation primarily through their blockade of alpha-1 rerceptors. Nebivolol is a lipophilic beta reseptor blocker of third generation with distinct beta-1 with selective and vasodilating properties. A number of experimental and human pharmological studies suggest that the vasodilatation is triggered via increasing vascular NO bioavailabilty which is a consequence of stimulation of NO release and antioxidant properties of this compound. The pharmocological profile is characterised by the significant antihypertensive effect as well as lowering of cardiac pre and after load. Nebivolol is well tolerated and does not appear to significantly influence glucose or plasma lipid metabolism. It is devoid of intrinsic sympathomimetic activity (ISA). This article will review patents, novel composition, pharmacology, haemodynamics, antihypertensive efficiency, metabolic effect and tolerability of nebivolol.

The influence of CYP2D6 phenotype on the clinical response of nebivolol in patients with essential hypertension

* The variability in drug metabolism has been recognized as an important factor in the occurrence of adverse effects or lack of therapeutic efficacy. * The metabolism of the third-generation beta(1)-receptor antagonist nebivolol has been shown to be highly dependent on cytochrome P450 2D6 enzymatic activity in preclinical studies. * This paper assesses the role of a cytochrome P450 2D6 gene defect on the antihypertensive response to nebivolol in a clinical setting. * Despite significant differences in drug disposition, the chronic administration of nebivolol produced similar efficacy and tolerability in hypertensive patients either characterized as poor or extensive metabolizers of the drug. * The study offers insight into the relative contribution of nebivolol enantiomers in systemic blood pressure control. Nebivolol is a beta(1)-adrenergic receptor antagonist with vasodilating properties used in the treatment of hypertension. It is administered as a racemic mixture (D- and L-nebivolol) and is highly metabolized by the cytochrome P-450 2D6 (CYP2D6). The purpose of this study was to determine the role of CYP2D6 phenotypes on the efficacy and tolerability of nebivolol during chronic administration to patients with essential hypertension. Two hundred and eighteen patients were genotyped and phenotyped for CYP2D6 activity, allowing to find and match 14 poor metabolizers (PMs) with 23 extensive metabolizers (EMs). Patients took rac-nebivolol 5 mg daily for 12 weeks. Blood pressure (BP), heart rate, adverse events, plasma levels of the two enantiomers D- and L-nebivolol and their corresponding hydroxymetabolites were assessed. The metabolic disposition of nebivolol was enantioselective and highly influenced by CYP2D6 phenotypes. Mean steady-state plasma concentrations of D- and L-nebivolol were 10- and 15-fold greater in PMs than in EMs, respectively (P < 0.0001). Despite these differences in the pharmacokinetics of nebivolol, EMs and PMs displayed similar BP responses. Mean reductions in sitting systolic and diastolic BPs were -11/-10 +/- 9/4 mmHg in EMs and -11/-9 +/- 10/5 mmHg in PMs. Side-effects were mild to moderate and not different between groups. Polymorphisms in the gene encoding CYP2D6 significantly influenced the metabolism of nebivolol, but not its antihypertensive efficacy and tolerability. The similar clinical response between EMs and PMs could be explained by the contribution of active hydroxylated metabolites of nebivolol to its antihypertensive actions in EMs.

Nebivolol

Nebivolol is a beta-blocker under U.S. Food and Drug Administration review for the treatment of hypertension. The unique pharmacologic properties of nebivolol include high specificity for the beta-1 receptor and a nitric oxide-mediated vasodilatory effect. The agent provides significant blood pressure reduction from baseline values as compared with placebo. Clinical trials have demonstrated that nebivolol reduces blood pressure similarly to atenolol, bisoprolol, amlodipine, nifedipine, lisinopril, and hydrochlorothiazide. The tolerability of nebivolol is similar to or better than that of these agents. In elderly patients (> or = 70 years of age) with clinically stable congestive heart failure, the addition of nebivolol to the treatment regimen improved the time to all-cause mortality and cardiovascular hospital admissions over that of placebo. If approved, nebivolol would likely be a viable alternative therapy for hypertension and heart failure; however, additional studies are needed in patients having coronary artery disease.

Nebivolol: a novel beta-blocker with nitric oxide-induced vasodilatation

Nebivolol is a novel beta1-blocker with a greater degree of selectivity for beta1-adrenergic receptors than other agents in this class and a nitric oxide (NO)-potentiating, vasodilatory effect that is unique among beta-blockers currently available to clinicians (nebivolol is approved in Europe and is currently under review in the US). A NO-potentiating agent such as nebivolol may have an important role in hypertensive populations with reduced endothelial function such as diabetics, African-Americans and those with vascular disease. Nebivolol is a racemic mixture with beta-blocker activity residing in the d-isomer; in contrast, l-nebivolol is far more potent in facilitating NO release. Nebivolol is unique among beta-blockers in that, at doses < 10 mg, it does not inhibit the increase in heart rate normally seen with exercise. The efficacy ofnebivolol has been tested successfully in clinical trials against other agents including other beta-blockers, angiotensin-converting enzyme-inhibitors and calcium channel antagonists in patients with hypertension, angina, and congestive heart failure. The tolerability of nebivolol has been shown to be superior to that of atenolol and metoprolol. In controlled clinical trials, nebivolol has a side effect profile that is similar to placebo, in particular as it relates to fatigue and sexual dysfunction. This article will review published clinical data regarding this cardioselective beta-blocker.

Efficacy and tolerability profile of nebivolol vs atenolol in mild‐to‐moderate essential hypertension: Results of a double‐blind randomized multicentre trial

The objective of this 12‐week double‐blind randomized multicentre study was to compare the efficacy and tolerability of nebivolol, a recently developed beta‐blocking agent with vasodilating properties, to the classical beta‐blocker atenolol. After a placebo run‐in phase, 205 mild‐to‐moderate middle‐age essential hypertensives were randomized to either nebivolol 5 mg daily (n = 105) or atenolol 100 mg daily (n = 100) over a period of 12 weeks. The primary endpoint of the study was the change in sitting systolic and diastolic blood pressure (SBP and DBP respectively) from baseline to week 12 of treatment. The two drugs induced similar significant antihypertensive effects, the SBP and DBP reduction amounting to–18.2 ± 14.0 and–14.6 ± 7.9 mmHg (mean ± SD) for atenolol and −19.1 ± 12.9 and −14.8 ± 7.1 for nebivolol (p < 0.01 for all). This was the case also for standing blood pressure. Sitting and standing heart rate values were significantly reduced by both drugs, the bradicardic response induced by nebivolol treatment being significantly less than atenolol. Distribution of responders and non‐ responders was similar for nebivolol and atenolol, while the former drug showed a better tolerability profile and a lower incidence of side‐effects. These data provide evidence, that, for the same antihypertensive effects, nebivolol shows a better tolerability profile than atenolol and a lower incidence of adverse effects.

Evaluation of the Efficacy and Tolerability of Nebivolol versus Lisinopril in the Treatment of Essential Arterial Hypertension: A Randomized, Multicentre, Double-blind Study

The main objective of this study was to compare the anti-hypertensive efficacy and safety of nebivolol (5 mg once daily) and lisinopril (20 mg once daily) given for 12 weeks in patients with mild to moderate essential hypertension. Fourteen centres participated in this randomized, double-blind parallel group study. Sixty-eight patients with uncomplicated mild-to-moderate hypertension were randomized, and sixty-five were eligible for the analysis of efficacy (intention-to-treat). Hypertensive patients were newly diagnosed, or previous antihypertensive therapy was withdrawn at least 1 month before active treatment, and were included in the study if their diastolic blood pressure (DBP) was >95 and <114 mmHg. The age range was 24-65 years. The primary endpoints of the study were: (i) response rate: patients were defined as "normalized" responders if their blood pressure values were <140/90 mmHg, or as "non-normalized" responders if the reduction in blood pressure was 10 mmHg or more, compared with baseline; (ii) changes in sitting blood pressure at the end of the study. The secondary endpoints were: standing blood pressure and sitting or standing heart rate (HR). Results showed that baseline sitting DBP was significantly different between groups. Analysis of covariance of the raw data performed with baseline as covariate demonstrated that the DBP and HR values were significantly lower in the nebivolol group at the 8th week. However, when an analysis of variance for repeated measures was performed, a significant reduction in sitting systolic blood pressure (SBP) (p < 0.0001), DBP (p < 0.0001) and HR (p < 0.0001) was observed throughout the study in both groups. No difference was observed between treatments, although for DBP, a significant interaction between treatment-weeks was observed (p = 0.016). There was also a statistically significant difference in favour of the nebivolol group in the distribution of responders and non-responders at week 8. Lisinopril and nebivolol were equally well tolerated. In conclusion, nebivolol was slightly more effective, in comparison with lisinopril, in terms of reduction in DBP. This greater efficacy was obtained without any increase in adverse effects, since both treatments were equally well tolerated.

Efficacy and tolerability of nebivolol in patients with mild-moderate hypertension

Efficacy and tolerability of nebivolol in patients with mild-moderate hypertension

Nebivolol - A Review

Nebivolol is a vasodilating β-blocker, which can be distinguished from other β-blockers by its haemodynamic profile. It combines β-adrenergic blocking activity with a vasodilating effect mediated by the endothelial Larginine nitric oxide (NO) pathway. The blood pressure lowering effect of nebivolol is linked to a reduction in peripheral resistance and an increase in stroke volume and preservation of cardiac output. Clinical trials have demonstrated that nebivolol reduces blood pressure similarly to atenolol, bisoprolol, amlodipine, nifedipine, lisinopril, and hydrochlorothiazide. The tolerability of nebivolol is similar to or better than that of these agents. In general, response rates to treatment are higher and the frequency and severity of adverse events are either comparable or lower with nebivolol. Endothelium-derived NO is important in the regulation of large arterial stiffness, which in turn is a major risk factor for cardiovascular disease. Therefore, antihypertensive drugs, such as nebivolol, that also improve endothelial function and decrease arterial stiffness, may contribute to a reduction in cardiovascular risk.Key words: Vasodilating β-blocker; nitric oxide (NO); peripheral resistance; arterial stiffness DOI: 10.3329/uhj.v6i2.7254University Heart Journal Vol. 6, No. 2, July 2010 pp.93-96