madman
Super Moderator
ABSTRACT
The management of arterial hypertension is very challenging in everyday clinical practice. Blood pressure control rates remain disappointingly low, despite intense efforts. Poor adherence to antihypertensive treatment is among the main causes of inadequate blood pressure control. Among the various parameters leading to poor adherence, medication adverse events seem to be the prevailing cause of treatment discontinuation. Β-blockers are a class of drugs commonly used in the management of hypertension. However, β-blockers use has been associated with various adverse events, among which, erectile dysfunction is a prevalent one. Accumulating evidence supports the detrimental role of β-blockers on erectile function. Older studies have shown contradictory findings, which however may be attributed to methodological errors related to the assessment of erectile function. More recent studies, however, unveiled the negative impact of this drug category on erectile function. Nevertheless, β-blockers represent a class of drugs with substantial within-class heterogeneity. Nebivolol presents a unique mode of action through enhanced nitric oxide bioavailability that may be associated with benefits on erectile function. Indeed, studies of nebivolol have shown improvement in erectile function, suggesting that nebivolol represents the only exception in this class of drugs in terms of erectile function
6. Nebivolol
Nebivolol is a third-generation β-blocker with cardioselectivity and vasorelaxant properties. While other vasodilating β-blockers, such as carvedilol and labetalol, exert their vasodilatory action via blockade of alpha-adrenergic receptors, nebivolol presents a unique vasodilating mode because it stimulates the endothelial nitric oxide synthetase, and thus increases the nitric oxide secretion in the penile tissue [85].
Experimental data indicate a favorable effect of nebivolol on hypertension-induced structural and functional alterations in the penile tissue. A study in spontaneously hypertensive rats showed lower cavernous smooth muscle, vascular smooth muscle, and collagen III values with nebivolol, compared to amlodipine or placebo; moreover, nebivolol was associated with higher endothelial nitric oxide expression in sinusoidal endothelium [86]. Another study in murine corpus cavernosum tissue found a significant increase in endothelial nitric oxide synthase activation and phosphorylation with nebivolol, compared with only a small increase with metoprolol [87]. In another mice model, nebivolol but not metoprolol improved penile endothelial function, as assessed by endothelium-dependent relaxation and reactive oxygen species production [88].
The unique effects of nebivolol on the erectile function within the βbloker class have been unveiled by both observational and randomized studies. In a large observational study of more than 1000 high-risk hypertensive patients treated with β-blockers, nebivolol was associated with a lower prevalence of ED (odds ratio: 0.27). In addition, patients on nebivolol exhibited higher IIEF scores than patients on other βblockers [80]. In another observational study of 1242 hypertensive patients, ED was independently and inversely related to nebivolol administration (odds ratio: 0.22) in the two younger quartiles of study participants [81].
Data from small randomized studies point towards the same direction. A randomized study of 131 hypertensive patients revealed that the mean number of satisfactory sexual intercourses per month remained constant with nebivolol, while it decreased significantly with atenolol (with or without chlorthalidone) [89]. MR NOED was a double-blind, randomized, crossover trial comparing the effects of nebivolol and metoprolol on erectile function. It was found that the IIEF erectile function subscore was decreased by metoprolol but not nebivolol, while nebivolol (but not metoprolol) improved other secondary sexual activity scores (orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction) [90]. Another study in 119 patients with coronary artery bypass surgery found that the incidence of any grade ED was significantly lower with nebivolol than with metoprolol (p = 0.036) [91].
Two other issues need to be noticed from the clinical point of view: the effects of switching and of combination antihypertensive therapy on erectile function. Regarding substitution of β-blocker therapy with nebivolol, in an open study of patients with ED while on β-blockers, it was found that erectile function score was improved in 69% of study participants who switched to nebivolol therapy [92]. Data on the effects of fixed combination therapy on erectile function is severely limited [93], and this aspect requires immediate attention since fixed combination therapy is recommended by the current European guidelines [2].
The above evidence is acknowledged by both scientific societies and administrative authorities. The summary of the product characteristics produced by the European Medicinal Agency states: “Available preclinical and clinical evidence in hypertensive patients has not shown that nebivolol has a detrimental effect on erectile function”. In addition, the recent ESC/ESH Guidelines for the management of arterial hypertension state for nebivolol that: “It has no adverse effect on the risk of new-onset diabetes and a more favorable side effect profile than classical β-blockers, including less adverse effects on sexual function” [2]. Finally, the recently published update of the ESH Working Group on sexual dysfunction highlighted the within-class differences regarding the effects of β-blockers on erectile function, focusing on the divergent effects of nebivolol [94]. Therefore, based on the aforementioned unique characteristics, nebivolol might be considered as a first-choice agent for the management of arterial hypertension in patients who value their sexual function.
The management of arterial hypertension is very challenging in everyday clinical practice. Blood pressure control rates remain disappointingly low, despite intense efforts. Poor adherence to antihypertensive treatment is among the main causes of inadequate blood pressure control. Among the various parameters leading to poor adherence, medication adverse events seem to be the prevailing cause of treatment discontinuation. Β-blockers are a class of drugs commonly used in the management of hypertension. However, β-blockers use has been associated with various adverse events, among which, erectile dysfunction is a prevalent one. Accumulating evidence supports the detrimental role of β-blockers on erectile function. Older studies have shown contradictory findings, which however may be attributed to methodological errors related to the assessment of erectile function. More recent studies, however, unveiled the negative impact of this drug category on erectile function. Nevertheless, β-blockers represent a class of drugs with substantial within-class heterogeneity. Nebivolol presents a unique mode of action through enhanced nitric oxide bioavailability that may be associated with benefits on erectile function. Indeed, studies of nebivolol have shown improvement in erectile function, suggesting that nebivolol represents the only exception in this class of drugs in terms of erectile function
6. Nebivolol
Nebivolol is a third-generation β-blocker with cardioselectivity and vasorelaxant properties. While other vasodilating β-blockers, such as carvedilol and labetalol, exert their vasodilatory action via blockade of alpha-adrenergic receptors, nebivolol presents a unique vasodilating mode because it stimulates the endothelial nitric oxide synthetase, and thus increases the nitric oxide secretion in the penile tissue [85].
Experimental data indicate a favorable effect of nebivolol on hypertension-induced structural and functional alterations in the penile tissue. A study in spontaneously hypertensive rats showed lower cavernous smooth muscle, vascular smooth muscle, and collagen III values with nebivolol, compared to amlodipine or placebo; moreover, nebivolol was associated with higher endothelial nitric oxide expression in sinusoidal endothelium [86]. Another study in murine corpus cavernosum tissue found a significant increase in endothelial nitric oxide synthase activation and phosphorylation with nebivolol, compared with only a small increase with metoprolol [87]. In another mice model, nebivolol but not metoprolol improved penile endothelial function, as assessed by endothelium-dependent relaxation and reactive oxygen species production [88].
The unique effects of nebivolol on the erectile function within the βbloker class have been unveiled by both observational and randomized studies. In a large observational study of more than 1000 high-risk hypertensive patients treated with β-blockers, nebivolol was associated with a lower prevalence of ED (odds ratio: 0.27). In addition, patients on nebivolol exhibited higher IIEF scores than patients on other βblockers [80]. In another observational study of 1242 hypertensive patients, ED was independently and inversely related to nebivolol administration (odds ratio: 0.22) in the two younger quartiles of study participants [81].
Data from small randomized studies point towards the same direction. A randomized study of 131 hypertensive patients revealed that the mean number of satisfactory sexual intercourses per month remained constant with nebivolol, while it decreased significantly with atenolol (with or without chlorthalidone) [89]. MR NOED was a double-blind, randomized, crossover trial comparing the effects of nebivolol and metoprolol on erectile function. It was found that the IIEF erectile function subscore was decreased by metoprolol but not nebivolol, while nebivolol (but not metoprolol) improved other secondary sexual activity scores (orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction) [90]. Another study in 119 patients with coronary artery bypass surgery found that the incidence of any grade ED was significantly lower with nebivolol than with metoprolol (p = 0.036) [91].
Two other issues need to be noticed from the clinical point of view: the effects of switching and of combination antihypertensive therapy on erectile function. Regarding substitution of β-blocker therapy with nebivolol, in an open study of patients with ED while on β-blockers, it was found that erectile function score was improved in 69% of study participants who switched to nebivolol therapy [92]. Data on the effects of fixed combination therapy on erectile function is severely limited [93], and this aspect requires immediate attention since fixed combination therapy is recommended by the current European guidelines [2].
The above evidence is acknowledged by both scientific societies and administrative authorities. The summary of the product characteristics produced by the European Medicinal Agency states: “Available preclinical and clinical evidence in hypertensive patients has not shown that nebivolol has a detrimental effect on erectile function”. In addition, the recent ESC/ESH Guidelines for the management of arterial hypertension state for nebivolol that: “It has no adverse effect on the risk of new-onset diabetes and a more favorable side effect profile than classical β-blockers, including less adverse effects on sexual function” [2]. Finally, the recently published update of the ESH Working Group on sexual dysfunction highlighted the within-class differences regarding the effects of β-blockers on erectile function, focusing on the divergent effects of nebivolol [94]. Therefore, based on the aforementioned unique characteristics, nebivolol might be considered as a first-choice agent for the management of arterial hypertension in patients who value their sexual function.
