Nebivolol: A unique drug in acute and chronic renal disorders.

Sir,

This letter is in context to an article published in Indian Journal of Pharmacology titled “Cost-effectiveness analysis of nebivolol and metoprolol in essential hypertension: A pharmacoeconomic comparison of antihypertensive efficacy of β-blockers.”[1] The authors concluded that nebivolol is more cost-effective as compared to metoprolol when the cost per reduction in blood pressure/day is considered. Metoprolol is the cardioselective beta-1 adrenoreceptor blocker conventionally used to treat hypertensive patients particularly in developing countries such as India and Iran. Nebivolol is a potent, highly cardioselective β-blocker with a unique hemodynamic profile compared with other cardioselective β-blockers, like metoprolol. The blood pressure lowering effects of nebivolol could be attributed to B1-adrenoceptor antagonism, modulation of the endothelial nitric oxide (NO) system, increasing the liberation of NO, resulting in coronary and systemic vasodilation, and thereby, a reduction in peripheral resistance and counteraction of endothelial dysfunction, and additionally, an increase in stroke volume, associareportted with a reduction in vascular resistance, resulting in a maintained cardiac output despite reduced heart rate [Figure 1]. Sorrentino et al. performed a study to investigate whether nebivolol has added effects on left ventricular (LV) dysfunction and remodeling early after myocardial infarction (MI) beyond its β1-receptor–blocking properties. They found novel evidence that nebivolol treatment is associated with beneficial effects on LV dysfunction, cardiomyocytes hypertrophy, and survival early after MI, likely independent of β1-receptor blocking effects because it was not observed with metoprolol therapy. Nebivolol induced effects on NO-mediated endothelial function, early endothelial progenitor cells, and inhibition of myocardial nicotinamide adenine dinucleotide phosphate oxidase early after MI.[2] Furthermore, other beneficial effect of nebivolol in a study by Oguz et al. performed to investigate effect of nebivolol on serum asymmetric dimethylarginine (ADMA) levels in hypertensive patients with type 2 diabetes in comparison with metoprolol, an another β-blocker. Similar reductions in blood pressure values were observed in both groups. They reported a significant increase in ADMA levels, a marker of endothelial dysfunction, during metoprolol treatment, whereas nebivolol had neutral effects on ADMA levels in patients with type 2 diabetes mellitus and hypertension.[3] Use of older generation β-blockers without ancillary vasodilating properties is associated with exercise intolerance and fatigue. This is thought to be a result of attenuation of β-AR-mediated increase in heart rate and cardiac output during exercise. These side effects seem to be much less common in patients treated with newer generation β-blockers like nebivolol because of its tendency to improve oxygen uptake or augment the reduction in systemic vascular resistance at peak exercise. Impaired functional sympatholysis is increasingly recognized as a cause of skeletal muscle malperfusion not only in hypertension but also in the normotensive elderly population and individuals with physical inactivity. Thus, inhibition of sympathetic vasoconstriction may constitute an additional mechanism by which exercise tolerance is improved with nebivolol. One beneficial effect of nebivolol in acute kidney injury is this point that pretreatment with oral nebivolol may decrease the incidence of contrast-induced nephropathy (CIN) in patients who underwent coronary angiography with renal dysfunction. Study by Avci et al. showed that the incidence of CIN was statistically significantly lower in the nebivolol group comparing with the metoprolol group,[4] but in another study by Akgüllü et al., they did not find any relation between the development of CIN and carvedilol, metoprolol or nebivolol usage.[5] Moreover, a pilot study revealed nebivolol improves renal function in patients who underwent angioplasty due to renal artery stenosis. Six months after revascularization, estimated glomerular filtration rate increased from 44.8 to 50.6 mL/min in the nebivolol group, and proteinuria decreased more in the nebivolol group compared to the control group. Taken together, studies show that nebivolol has better efficacy than metoprolol in terms of reducing both systolic as well as diastolic blood pressure, LV dysfunction, and remodeling early after MI. In the above mentioned study by Patel et al., it was evident that nebivolol produces less adverse effects and ensures a better quality of life than metoprolol. With consideration of this adage “to first, do no harm” it seems that nebivolol is superior to metoprolol for long-term therapy in essential hypertension, post MI, and prevention of contrast-induced acute kidney injury, and supports this research article for consideration of nebivolol in decision-making of therapeutic management of hypertension and various states of kidney diseases.

Figure 1

L-arginine-nitric oxide pathway and effect of it on various internal organs. Nebivolol induces endothelial nitric oxide synthase

Financial Support and Sponsorship

Nil.

Conflicts of Interest

There are no conflicts of interest.