Nebivolol Efficacy and Safety in Patients with Stage I‐II Hypertension

Abstract

Background: Nebivolol is a novel, β 1 -adrenergic receptor blocker with vasodilatory properties mediated through activation of the L-arginine/nitric oxide pathway. Hypothesis: This multicenter, double-blind, parallel-group, placebo-controlled study investigated the antihypertensive efficacy and safety of nebivolol in patients with stage I through stage II hypertension (sitting diastolic blood pressure [SiDBP] ≥95 mm Hg and ≤109 mm Hg). Methods: A total of 811 patients were randomized to placebo or nebivolol 5 mg, 10 mg, or 20 mg once daily for 12 weeks. The primary efficacy endpoint was the reduction in mean trough SiDBP from baseline. Results: At study end, the least squares mean reductions in trough SiDBP from baseline with nebivolol 5 mg, 10 mg, and 20 mg were −7.8 mm Hg, −8.5 mm Hg, and −9.1 mm Hg, respectively, compared with −4.6 mm Hg for placebo (P = .002 for nebivolol 5 mg, P<.001 for nebivolol 10 mg and 20 mg, vs placebo). Nebivolol treatment also produced reductions in trough sitting systolic blood pressure; however, only the 20 mg dose was statistically significant compared with placebo (−6.7 mm Hg vs −0.4 mm Hg; P<.001). Response rates (defined as an average trough SiDBP <90 mm Hg or a decrease by ≥10 mm Hg from baseline at the end of the study) ranged from 66.0% to 68.9% with nebivolol 5-20 mg, compared with 49.3% with placebo (P≤.009). Nebivolol 5 mg and 10 mg doses were well tolerated, with an overall adverse event incidence comparable to placebo. Conclusions: Once-daily nebivolol is an effective antihypertensive agent in patients with stage I-II hypertension.

Efficacy and safety of nebivolol in Hispanics with stage I-II hypertension: a randomized placebo-controlled trial

“…The results of this study support findings from other nebivolol trials in hypertension [Greathouse, 2010;Neutel et al 2009;Saunders et al 2007;Weiss et al 2007;Van Nueten et al 1998, 1997: nebivolol is efficacious in reducing BP in participants with stage III hypertension, associated with an AE rate similar to that of placebo, and a low rate of AEs commonly associated with beta-blocker use (dyspnea, 0%; fatigue, 0%; sexual dysfunction, 0.7%) [Munzel and Gori, 2009]. The relatively low incidence of AEs in this study and other nebivolol clinical trials [Ambrosioni and Borghi, 2005] may be attributable to its high ß1-selectivity and NO-mediated vasodilatory effects [Munzel and Gori, 2009].…”

Adding nebivolol to ongoing antihypertensive therapy improves blood pressure and response rates in patients with uncontrolled stage I–II hypertension

“…Overall, the DBP and SBP reductions as well as the response rates observed in this trial are confirmatory of the BP reductions observed in the three registration trials of nebivolol monotherapy vs placebo conducted in over 2000 patients with stage I-II hypertension. 14,15,26 Use of antihypertensive therapies with complementary mechanisms of action is advocated for optimal control of BP due to the multifactorial aetiology of hypertension. 5 Perhaps for this reason, combination therapy of b-blockers with ACE inhibitors or ARBs has not always demonstrated additive benefits, as they both target the reninangiotensin system.…”

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

“…In the three trials that were pooled in our analysis [Greathouse, 2010;Saunders et al 2007;Weiss et al 2007], the observed rates of ED (0.5% of men) and OH (0.2%) were relatively low. (OH is a phenomenon that has been estimated to occur in 5-33% of the elderly and may be caused by various antihypertensive medications, including β-blockers [Verhaeverbeke and Mets, 1997].)…”

“…All data reported in this publication were pooled from three similarly designed phase III, Greathouse, 2010]. Trials NEB-MD-202 and NEB-MD-302 were conducted in the US; trial NEB-MD-305 was conducted in the US, UK, Belgium, and the Netherlands.…”

“…Although available data suggest that treatment with older-generation β-blockers (mainly atenolol) is associated with a reduction of cardiovascular morbidity and mortality in younger (<60 years of age) but not older (≥60 years) patients with uncomplicated hypertension [Khan and McAlister, 2006;Messerli et al 1998], there are no randomized, prospective, placebo-controlled trials that examined the effects of nebivolol treatment, short or long term, based on patients' age. This post hoc analysis evaluated the efficacy and safety of nebivolol monotherapy in a pooled sample from three US registration trials [Greathouse, 2010;Saunders et al 2007;Weiss et al 2007], stratified by age quartiles. …”