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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nebivolol is a highly selective beta1-adrenergic blocker that also enhances nitric oxide bioavailability via the L-arginine-nitric oxide pathway, leading to vasodilation and decreased peripheral vascular resistance. It is marketed in Europe for the treatment of hypertension and heart failure and is currently being reviewed for use in the US by the Food and Drug Administration. Nebivolol appears to be well tolerated with an adverse event profile that is at least similar, if not better, than that of other beta-adrenergic blockers. Studies suggest that long-term therapy with nebivolol improves left ventricular function, exercise capacity, and clinical endpoints of death and cardiovascular hospital admissions in patients with stable heart failure. To date, it is one of the only beta-adrenergic blockers that have been exclusively studied in elderly patients. Additionally, the unique mechanism of action of nebivolol makes it a promising agent for treatment of chronic heart failure in high-risk patient populations, such as African Americans. This article will review the pharmacologic and pharmacokinetic properties of nebivolol as well as clinical studies assessing its efficacy for the treatment of heart failure.
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PMID:Nebivolol in the treatment of chronic heart failure. 1807 16

Nebivolol is a third generation beta-blocker, which can be distinguished from other beta-blockers by its hemodynamic profile. It combines beta-adrenergic blocking activity with a vasodilating effect mediated by the endothelial L-arginine nitric oxide (NO) pathway. The effects of nebivolol have been compared with other beta-blockers and also with other classes of antihypertensive agents. In general, response rates to treatment are higher, and the frequency and severity of adverse events are either comparable or lower with nebivolol. Nebivolol is also effective in reducing cardiovascular morbidity and mortality in elderly patients with heart failure, regardless of the initial ejection fraction. Endothelium-derived NO is important in the regulation of large arterial stiffness, which in turn is a major risk factor for cardiovascular disease. Treatment with nebivolol increases the release of NO from the endothelium and improves endothelial function, leading to a reduction in arterial stiffness. Decreased arterial stiffness has beneficial hemodynamic effects including reductions in central aortic blood pressure. Unlike first generation beta-blockerrs, vasodilator beta-blockerrs such as nebivolol have favorable hemodynamic effects, which may translate into improved cardiovascular outcomes in patients with hypertension.
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PMID:A review of the safety and efficacy of nebivolol in the mildly hypertensive patient. 1820 Aug 10

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.
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PMID:Nebivolol: more than a highly selective Beta blocker. 1822 Nov 15

Overload-induced heart failure is associated with enhanced apoptosis of cardiomyocytes, and increased mechanical load is an inductor of this apoptosis. It is unknown whether nebivolol, a third generation beta(1)-adrenoceptor antagonist, possesses properties that can attenuate this apoptosis. Multicellular preparations from rabbit hearts were mounted in a culture system that allows for measurement of contractile parameters over several days. Culturing these muscles on a constant high preload induces apoptosis of the cardiomyocytes. Of each heart, 1 preloaded muscle preparation was treated with nebivolol (10(-6) mol/l), 1 preloaded without continuous exposure to nebivolol (positive control) and 1 unloaded (negative control). After 48 h of continuous loaded contractions, apoptosis was assessed by TUNEL-assay to confirm that nuclei of myocytes were affected, or by DNA-ladder intensity analysis for semiquantification. Maximal twitch force development was slightly, but significantly, lower in preparations contracting in presence of nebivolol (compared to solvent) while twitch-timing parameters were similar. After 48 h of continuous contractions, no additional differences were observed between the groups regarding contractile parameters. DNA-ladder analysis showed a similar rate of apoptosis in presence of nebivolol. Nebivolol does not increase, nor decrease, the rate of load-induced cardiomyocyte apoptosis.
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PMID:Load-induced cardiomyocyte apoptosis in cultured multicellular myocardial preparations is unaltered in presence of the beta-adrenoceptor antagonist nebivolol. 1912 77

beta-blockers are among the most widely used drugs in the prevention and treatment of cardiovascular disease, although they are associated with increased peripheral resistance. Third-generation beta-blockers avoid this adverse effect by inducing vasodilation through different mechanisms. In particular, nebivolol, a highly selective blocker of beta(1)-adrenergic receptors, is the only beta-blocker known to induce vascular production of nitric oxide, the main endothelial vasodilator. The specific mechanism of nebivolol is particularly relevant in hypertension, where nitric oxide dysfunction occurs. Indeed, nebivolol is able to reverse endothelial dysfunction. Nebivolol induces nitric oxide production via activation of beta(3)-adrenergic receptors, which can explain the good metabolic profile observed after treatment with this drug. Moreover, nebivolol can also stimulate the beta(3)-adrenergic receptor-mediated production of nitric oxide in the heart, and this stimulation can result in a greater protection against heart failure. In conclusion, nebivolol has a unique profile among antihypertensive drugs, adding to a very high selectivity against beta(1) adrenergic receptors, and an agonist action on beta(3) receptors and nitric oxide (NO), which has led to clinically significant improvements in hypertensive patients.
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PMID:Nitric oxide mechanisms of nebivolol. 1944 16

Beta (beta) blockers are widely used for treatment of cardiovascular and noncardiovascular diseases. Nevertheless, their mechanism of action is not fully understood and differs significantly among agents in this class. Chronic increases in adrenergic activity in heart failure result in desensitization of cardiac beta-adrenergic receptor signal transduction and adverse effects on myocytes. By reducing heart rate and decreasing myocardial workload, the pathologic remodeling of the heart may be reversed with beta-blocking agents. Among beta-blockers, there are clear differences in pharmacodynamic and pharmacokinetic properties. Newer beta-blockers differ from older agents with respect to beta-adrenoceptor affinity and selectivity and partial agonist activity, which may affect their mechanism of action and be important in clinical use.The first beta-antagonist compounds were nonselective; the next generation of beta-blockers was selective for beta1-receptors. The most recent beta-blockers may be nonselective or selective, and they have the additional ancillary property of vasodilation. Nebivolol is among the newer third-generation beta-blockers. It is unique in the class, since apart from its cardioselectivity, it also produces nitric oxide-mediated vasodilation. As a result, its hemodynamic profile is clearly different from those of traditional beta-blockers. This review will evaluate this class of agents and the basis for their differences in clinical use.
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PMID:Evolving mechanisms of action of beta blockers: focus on nebivolol. 1952 11

Beta-blockers are prescribed for a variety of cardiovascular conditions including hypertension, heart failure, primary treatment of myocardial infarction (MI), and secondary prevention of ischemic cardiac events. Yet they remain underprescribed in populations at increased risk for cardiovascular disease because of tolerability and safety concerns. Beta-blockers are heterogeneous with respect to pharmacokinetic and pharmacodynamic effects. "Original" agents were nonselective, blocking both beta1-adrenoceptors and beta2-adrenoceptors. Later, new agents were developed with selectivity for beta1-adrenoceptors, and were subsequently followed by beta-blockers, which exhibit additional effects, such as vasodilation. Among newer agents, labetalol, carvedilol, and nebivolol have been approved for use in the United States. Nebivolol possesses both beta1-selectivity and nitric oxide-mediated vasodilatory effects, while carvedilol has attractive effects on insulin resistance and exhibits antioxidant effects. Newer beta-blockers may overcome concerns about efficacy, adverse effects, and tolerability, while delivering cardiovascular protection.
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PMID:Realities of newer beta-blockers for the management of hypertension. 1958 33

Nebivolol is a third-generation beta-adrenergic receptor antagonist (beta-blocker) with high selectivity for beta(1)-adrenergic receptors. In addition, it causes vasodilatation via interaction with the endothelial L-arginine/nitric oxide (NO) pathway. This dual mechanism of action underlies many of the haemodynamic properties of nebivolol, which include reductions in heart rate and blood pressure (BP), and improvements in systolic and diastolic function. With respect to BP lowering, the NO-mediated effects cause a reduction in peripheral vascular resistance and an increase in stroke volume with preservation of cardiac output. Flow-mediated dilatation and coronary flow reserve are also increased during nebivolol administration. Other haemodynamic effects include beneficial effects on pulmonary artery pressure, pulmonary wedge pressure, exercise capacity and left ventricular ejection fraction. In addition, nebivolol does not appear to have adverse effects on lipid metabolism and insulin sensitivity like traditional beta-blockers. The documented beneficial haemodynamic effects of nebivolol are translated into improved clinical outcomes in patients with hypertension or heart failure. In patients with hypertension, the incidence of bradycardia with nebivolol is often lower than that with other currently available beta-blockers. This, along with peripheral vasodilatation and NO-induced benefits such as antioxidant activity and reversal of endothelial dysfunction, should facilitate better protection from cardiovascular events. In addition, nebivolol has shown an improved tolerability profile, particularly with respect to events commonly associated with beta-blockers, such as fatigue and sexual dysfunction. Data from SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure) showed that significantly fewer nebivolol versus placebo recipients experienced the primary endpoint of all-cause mortality or cardiovascular hospitalization. The benefits of nebivolol therapy were shown to be cost effective. Thus, nebivolol is an effective and well tolerated agent with benefits over and above those of traditional beta-blockade because of its effects on NO release, which give it unique haemodynamic effects, cardioprotective activity and a good tolerability profile.
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PMID:Nebivolol: haemodynamic effects and clinical significance of combined beta-blockade and nitric oxide release. 2003 Apr 24

The beneficial effects of beta blockers in younger patients with heart failure (HF) due to systolic dysfunction are well established. However, data from patients > or =70 years old with diabetes mellitus and HF are lacking. The Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with heart failure [SENIORS] tested the efficacy of the vasodilator beta blocker nebivolol in patients > or =70 years old with HF and impaired or preserved left ventricular ejection fraction. In the present analysis, we evaluated the association between diabetes mellitus and baseline glucose levels on the primary outcome (all-cause mortality and cardiovascular hospitalization) and secondary end points, including all-cause mortality, cardiovascular hospitalizations, and cardiovascular mortality. Of 2,128 patients, 555 (26.1%) had diabetes mellitus. Of the 555 patients with diabetes mellitus, 223 (40.2%) experienced the primary end point compared to 484 (30.8%) of the 1,573 nondiabetic patients (p <0.001). For the nondiabetic patients, the rate of the primary outcome for placebo compared to nebivolol was 33.7% for the placebo group and 27.8% for the nebivolol group (hazard ratio 0.78, 95% confidence interval 0.65 to 0.93; p = 0.006). In the diabetic subset, the rate was 40.3% for the placebo group and 40.1% for the nebivolol group (hazard ratio 1.04, 95% confidence interval 0.80 to 1.35, p = 0.773). The subgroup interaction p value was 0.073. The baseline glucose levels in the nondiabetic patients did not significantly affect the outcomes. The effect of diabetes mellitus on outcome was independent of the left ventricular ejection fraction and was most pronounced in those with HF due to a nonischemic etiology. In conclusion, in patients > or =70 years old with HF, diabetes mellitus was associated with a worse prognosis. Nebivolol was less effective in the patients with diabetes and HF than in those with HF but without diabetes who were > or =70 years old.
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PMID:Influence of diabetes mellitus and hyperglycemia on prognosis in patients > or =70 years old with heart failure and effects of nebivolol (data from the Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with heart failure [SENIORS]). 2060 52

Heart failure is a common and disabling condition with morbidity and mortality that increase dramatically with advancing age. Large observational studies, retrospective subgroup analyses and meta-analyses of clinical trials in systolic heart failure, and recently published randomized studies have provided data supporting the use of beta-blockers as a baseline therapy in heart failure in the elderly. Despite the available evidence about beta-blockers, this therapy is still less frequently used in elderly compared to younger patients. Nebivolol is a third-generation cardioselective beta-blocker with L-arginine/nitric oxide-induced vasodilatory properties, approved in Europe and several other countries for the treatment of essential hypertension, and in Europe for the treatment of stable, mild, or moderate chronic heart failure, in addition to standard therapies in elderly patients aged 70 years old or older. The effects of nebivolol on left ventricular function in elderly patients with chronic heart failure (ENECA) and the study of effects of nebivolol intervention on outcomes and rehospitalization in seniors with heart failure (SENIORS) have been specifically aimed to assess the efficacy of beta-blockade in elderly heart failure patients. The results of these two trials demonstrate that nebivolol is well tolerated and effective in reducing mortality and morbidity in older patients, and that the beneficial clinical effect is present also in patients with mildly reduced ejection fraction. Moreover, nebivolol appears to be significantly cost-effective when prescribed in these patients. However, further targeted studies are needed to better define the efficacy as well as safety profile in frail and older patients with comorbid diseases.
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PMID:Clinical and economic aspects of the use of nebivolol in the treatment of elderly patients with heart failure. 2115 40


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