Nebivolol demonstrates efficacy and favorable safety profile in treatment of hypertension

Phase 3 clinical trials demonstrated that the once-daily, highly selective beta blocker nebivolol lowers blood pressure in a dose-dependent manner and is well tolerated at all doses, according to presenters at the 21st annual scientific meeting of the American Society of Hypertension (ASH), in New York, NY.

Nebivolol's actions among beta blockers are unique in that its vasodilating properties are most likely mediated through the l-arginine/nitric oxide pathway, said Joel M. Neutel, MD, lead investigator of a pooled analysis of 2 efficacy studies of nebivolol in patients with hypertension. In addition to increasing nitric oxide synthesis, nebivolol also appears to increase the bioavailability of nitric oxide in endothelial cells.

"Its impact on arterial compliance and endothelial function differentiates it from other beta blockers," said Dr Neutel, associate professor of medicine, University of California, Irvine, Calif. "In this regard, it acts much like an ACE inhibitor."

Reductions in trough sitting systolic blood pressure obtained with nebivolol were 2.4 mmHg (1.25 mg) to 7.6 mmHg (40 mg). Patients assigned to placebo had a 0.7-mmHg increase in sitting systolic blood pressure (P=.005 for 2.5 mg vs placebo; P <.001 for all higher doses vs placebo).

Trough sitting diastolic blood pressure was reduced by 6.9 mmHg (1.25 mg) to 10.1 mmHg (40 mg) in the nebivolol recipients, compared with 3.8 mmHg in the placebo groups (P=.005 for 2.5 mg vs placebo; P<.001 for all higher doses vs placebo).

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

The antihypertensive efficacy for nebivolol was consistent across gender and race, Dr Neutel said.

Some 88.6% of the pooled nebivolol group and 82.1% of the placebo group completed the study. The rate of adverse events in both the nebivolol and placebo groups was 2.6%.

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, SC. Dr Basile performed a pooled tolerability analysis of 3 large-scale trials in 2,016 patients with mild-to-moderate hypertension who had been randomized to placebo or various doses 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% of the placebo recipients, Dr Basile said.

Low rates also were observed for adverse events commonly associated with beta blocker use, including dyspnea (0.1% to 0.6%), depression (0.0% to 0.3%), bradycardia (0.2% to 0.4%), and erectile dysfunction (0.0% to 0.3%), he said.