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Nebivolol

Haemodynamic Effects and Clinical Significance of Combined β-Blockade and Nitric Oxide Release

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Abstract

Nebivolol is a third-generation β-adrenergic receptor antagonist (β-blocker) with high selectivity for β1-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 β-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 β-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 β-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 β-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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Acknowledgements

Editorial assistance with English and preparation for submission was provided by Nicola Ryan of Wolters Kluwer with support from A Menarini Farmaceutica Internazionale srl, Florence, Italy. Professor Metra has received honoraria for preparation for advisory boards and meetings organized by companies involved in cardiovascular research, including Corthera, Merck, Cardiokime and Ostuka. The other authors have no conflicts of interest that are directly relevant to the content of this article.

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  1. Department of Cardiology, Institute for Cardiovascular Research VU, VU University Medical Center, Amsterdam, the Netherlands

    Otto Kamp

  2. Section of Cardiovascular Disease, Department of Experimental and Applied Sciences, University of Brescia, Faculty of Medicine, c/o Spedali Civili; Piazza Spedali Civili, 25123, Brescia, Italy

    Marco Metra, Silvia Bugatti, Luca Bettari, Natalia Petrini & Livio Dei Cas

  3. Department of Internal Medicine and Biomedical Sciences, University of Parma, Parma, Italy

    Alessandra Dei Cas

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Kamp, O., Metra, M., Bugatti, S. et al. Nebivolol. Drugs 70, 41–56 (2010). https://doi.org/10.2165/11530710-000000000-00000

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