Novel Cardioselective Beta-Blocker Potent Antihypertensive

June 3, 2007
Wayne Kuznar

Internal Medicine World Report, June 2006, Volume 0, Issue 0

From the American Society of Hypertension

NEW YORK CITY?A novel, once-daily, highly-selective beta-blocker now in phase 3 clinical studies lowers blood pressure (BP) in a dose-dependent manner and is well tolerated at all doses, presenters said at the 21st annual scientific meeting of the American Society of Hypertension.

The investigational agent, nebivolol (Mylan), offers unique beta-blockade actions mediated through the L-arginine/ nitric oxide (NO) pathway, said Joel M. Neutel, MD, associate professor of medicine, University of California, Irvine. Through this pathway, nebivolol produces endothelium-dependent vasodilation.

In addition to increasing NO synthesis, it also appears to increase the bio- availability of NO in endothelial cells.

"Its impact on arterial compliance and endothelial function differentiates it from other beta-blockers," said Dr Neutel. "In this regard, it acts much like an angiotensin-converting-enzyme inhibitor."

"I expect that it will be an alternative as a first-line agent for the treatment of hypertension. It works in all races and subgroups, including diabetics." ?Joel M. Neutel, MD

"I expect that it will be an alternative as a first-line agent for the treatment of hypertension," he said. "It works in all races and subgroups, including diabetics."

He was lead investigator in a pooled analysis of 2 randomized, multicenter, double-blind trials that compared nebivolol with placebo in 1716 adults with mild-to-moderate hypertension.

Patients were randomized to 12 weeks of treatment with placebo or nebivolol (1.25, 2.5, 5, 10, 20, or 40 mg/d) in one study, and placebo or nebivolol (5, 10, or 20 mg/d) in the second study.



Trough sitting systolic BP was reduced by 2.4 mm Hg (1.25 mg) to 7.6 mm Hg (40 mg) in patients assigned to nebivolol. Placebo recipients experienced a 0.7-mm Hg increase in sitting systolic BP ( = .005 for 2.5 mg vs placebo; <.001 for all higher doses vs placebo).



Trough sitting diastolic BP was reduced by 6.9 mm Hg (1.25 mg) to 10.1 mm Hg (40 mg) in the nebivolol patients, compared with 3.8 mm Hg in the placebo groups ( = .005 for 2.5 mg vs placebo; <.001 for all higher doses vs placebo).


At the 1.25-mg dose, 45.8% of nebivolol recipients were considered treatment responders, defined as achieving a sitting diastolic BP <90 mm Hg or a reduction of at least 10 mm Hg from baseline. The response rate increased to 65.1% ( <.001 vs placebo) at the 20-mg dose of nebivolol.

The efficacy of the drug was consistent across genders and races, said Dr Neutel.

Selective affinity for the beta1 receptor (cardioselective agents) has been associated with a favorable safety and tolerability profile compared with nonselective beta-blockers, said Jan N. Basile, MD, professor of medicine, Medical University of South Carolina, Charleston. He performed a pooled tolerability analysis of 3 trials involving 2016 patients with mild-to-moderate hypertension who had been randomized to placebo or various dosages of nebivolol.

Nebivolol was well tolerated at all doses, with no significant difference versus placebo for overall discontinuations (13.4% vs 17.6%, respectively) or discontinuation due to adverse events (2.6% vs 2.0%, respectively).

Fatigue, a common problem with many other beta-blockers, occurred in 2.6% to 5.5% of the nebivolol-treated patients, depending on the dose, compared with 1.5% in the placebo group, said Dr Basile.