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Nebivolol

A Review of its Use in the Management of Hypertension and Chronic Heart Failure

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Summary

Abstract

Nebivolol is a third-generation β-adrenoceptor antagonist. It differs from other β-adrenoceptor antagonists as it combines highly selective β1-adrenoceptor antagonist properties with nitric oxide-mediated vasodilatory actions and beneficial effects on endothelial function. Nebivolol is 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 (CHF) in addition to standard therapies in elderly patients aged ≥70 years.

Nebivolol is an effective antihypertensive agent and is well tolerated in patients with hypertension. The drug also effectively decreased the composite endpoint of mortality and cardiovascular hospital admission in elderly patients with CHF and was generally well tolerated in this population. Nebivolol should be considered as an alternative first-line treatment option for patients with uncomplicated mild to moderate essential hypertension and in elderly patients with CHF.

Pharmacological Properties

Nebivolol is a highly selective β1-adrenoceptor antagonist that also causes vasodilation via interaction with the endothelial L-arginine/nitric oxide pathway. The drug appears to increase nitric oxide production and release, and to decrease nitric oxide degradation. Nebivolol lowers heart rate and blood pressure (BP), and improves systolic and diastolic function. Nitric oxide-mediated effects of nebivolol include decreasing systemic vascular resistance and large artery stiffness, and nebivolol may also reverse endothelial dysfunction.

Following oral administration, nebivolol is rapidly absorbed. Although metabolism of nebivolol to its numerous metabolites can vary substantially between extensive and poor metabolisers, resulting in a wide range of bioavailability, there appears to be little difference in the clinical outcome between different types of metabolisers.

Dosage adjustments are recommended in patients with renal impairment and a lower starting dosage is recommended for elderly patients. Nebivolol is contraindicated in patients with hepatic impairment.

Therapeutic Efficacy

In randomised, double-blind, parallel-group studies in patients with mild to moderate essential hypertension, nebivolol was at least as effective at lowering BP as other antihypertensive drugs, including other β-adrenoceptor antagonists.

Nebivolol was more effective than placebo in lowering the incidence of the primary composite endpoint of all-cause mortality or cardiovascular hospitalisation in SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure), a study in elderly patients (aged ≥70 years) with CHF. A significantly greater improvement in left ventricular ejection fraction in nebivolol versus placebo recipients was also seen in elderly patients with CHF in the ENECA (Efficacy of Nebivolol in the treatment of Elderly patients with Chronic heart failure as Add-on therapy to ACE inhibitors or angiotensin II receptor blockers, diuretics, and/or digitalis) study and a substudy of SENIORS.

Tolerability

Nebivolol was equally or better tolerated than comparator agents in hypertension trials. The most frequent adverse events in recipients of nebivolol monotherapy were transient headache, dizziness and tiredness.

In elderly patients with CHF, the incidence of most adverse events was similar in nebivolol and placebo recipients. Bradycardia was one of the most common adverse events in nebivolol recipients, but not in placebo recipients.

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  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 1311, New Zealand

    Marit D. Moen & Antona J. Wagstaff

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  1. Marit D. Moen
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  2. Antona J. Wagstaff
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Correspondence to Marit D. Moen.

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Moen, M.D., Wagstaff, A.J. Nebivolol. Drugs 66, 1389–1409 (2006). https://doi.org/10.2165/00003495-200666100-00007

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