Efficacy and tolerability of nebivolol: does age matter? A retrospective analysis of three randomized, placebo-controlled trials in stage I–II hypertension

Abstract

Abstract:Objectives: This retrospective analysis examined the efficacy and tolerability of nebivolol, a ß 1 -selective, vasodilatory β-blocker, in four different age groups of patients with hypertension. Methods: Data were pooled from three 12-week, randomized, placebo-controlled trials (placebo, n = 205; nebivolol [1.25-30/40 mg/day], n = 1811) and stratified into age quartiles (Group 1: 22-46 years; Group 2: 47-53 years; Group 3: 54-62 years; Group 4: 63-84 years). Only patients treated with placebo and the three commonly used nebivolol dosages (5, 10, and 20 mg/day) are presented. Baseline-to-endpoint changes in trough sitting diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR) were analyzed for each age quartile using an analysis of covariance (ANCOVA) model. Tolerability was assessed by means of adverse event (AE) rates. Results: The analysis comprised 205 placebo-treated patients and 1380 patients treated with nebivolol dosages of 5, 10, or 20 mg/day. Older age was associated with higher SBP values at baseline. In all age groups, each of the three most frequently used nebivolol dosages significantly reduced DBP, compared with placebo (-9.1 to -11.8 mmHg versus -3.4 to -5.9 mmHg; p ≤ 0.008 overall). For SBP, a statistically significant effect versus placebo was observed for all dosages and age groups except for 5 and 10 mg/day in Group 4. Within each group, treatment with nebivolol (all three dosages) and placebo resulted in similar AE rates (nebivolol: 26.1-36.6%; placebo: 36.2-42.6%) and AE-related discontinuation rates (1.8-3.8% versus 0-4.3%). In each age group, there were no significant nebivolol-placebo differences in the rates of patients who experienced clinically significant changes or abnormal endpoint levels of metabolic parameters. Conclusions: This retrospective analysis suggests that nebivolol monotherapy is efficacious and well tolerated across various age groups, with the efficacy in reducing SBP somewhat diminishing in patients over 62 years of age. The changes in hypertension type, severity, and prevalence across age groups pose notable challenges in clinical practice. For example, older age is also associated with an increased prevalence of comorbidities and polypharmacy, whereas younger age is a key determinant of poor therapy adherence [Briesacher et al. 2008;Fischer et al. 2010]. In addition, antihypertensive medication itself is independently associated with a higher risk of adverse events (AEs) such as erectile dysfunction (ED) [Cordero et al. 2010;Düsing, 2005;Ko et al. 2002;Shiri et al. 2007] and orthostatic hypotension (OH) [Cleophas and van Marum, 2003], which may affect quality of life and lead to treatment discontinuation in both younger and older patients [Fogari and Zoppi, 2004]. Therefore, patient age should be carefully taken into consideration when selecting antihypertensive therapy [Carlberg and Nilsson, 2010]. KeywordsNebivolol, a ß 1 -selective blocker with vasodilatory properties that are thought to be mediated by nitric oxide (NO) [Münze...

Nebivolol Monotherapy in Younger Adults (Younger Than 55 Years) With Hypertension: A Randomized, Placebo‐Controlled Trial

“…Our efficacy results are generally in agreement with findings of the age‐stratified pooled analysis of 3 pivotal nebivolol trials (N=1585) and a German observational study (N=5031), which both showed efficacy of nebivolol across the entire age spectrum of adulthood. In the German study, a stronger effect for both DBP and SBP was observed among younger patients (younger than 59 years) vs older patients, and, in the pooled analysis, a significant effect on SBP in the oldest group (63–84 years) was observed only with the dosage of 20 mg/d . However, the extent to which our trial can be compared with those two studies is limited: The German study and the 3 pooled pivotal studies were all fixed‐dose trials, plus the German study was open‐label, with a majority of patients taking other antihypertensives .…”

“…The placebo‐subtracted DBP and SBP reductions in our trial were similar to those seen in pivotal, fixed‐dose trials of nebivolol, in which participants' mean age was 54 years . Our efficacy results are generally in agreement with findings of the age‐stratified pooled analysis of 3 pivotal nebivolol trials (N=1585) and a German observational study (N=5031), which both showed efficacy of nebivolol across the entire age spectrum of adulthood. In the German study, a stronger effect for both DBP and SBP was observed among younger patients (younger than 59 years) vs older patients, and, in the pooled analysis, a significant effect on SBP in the oldest group (63–84 years) was observed only with the dosage of 20 mg/d .…”

“…In the German study, a stronger effect for both DBP and SBP was observed among younger patients (younger than 59 years) vs older patients, 24 and, in the pooled analysis, a significant effect on SBP in the oldest group (63-84 years) was observed only with the dosage of 20 mg/d. 18 However, the extent to which our trial can be compared with those two studies is limited: The German study and the 3 pooled pivotal studies were all fixed-dose trials, 18,24 plus the German study was open-label, with a majority of patients taking other antihypertensives. 24 In addition, a high percentage of patients who experienced DBP reduction ≥8 mm Hg (Figure 2) is encouraging, considering the fact that in individuals younger than 50 years, DBP is a stronger predictor of coronary heart disease than SBP or pulse pressure.…”

Additivity of nebivolol/valsartan single‐pill combinations versus other single‐pill combinations for hypertension

“…These results support the notion that effective BP reduction with a combination of a β‐blocker and a RAAS inhibitor may depend on the particular drugs combined. In multiple studies, both nebivolol and valsartan monotherapies have been shown to be safe and effective in patients with hypertension, including in populations susceptible to treatment‐resistant hypertension (eg, elderly, black) . This analysis of the additivity of the nebivolol/valsartan SPCs compared with other approved SPCs for the treatment of hypertension further supports its clinical utility.…”

Nebivolol: Does the key lie in β3 agonism?

“…in the subgroup analysis [41] and especially beneficial in the group of young patients [42], a special target for the incidence of adrenergic hypertension.…”