Nebivolol can lower DBP by 15 mm Hg or more.

NEW ORLEANS—Two pooled analyses of the newest beta blocker, nebivolol, demonstrate that it is effective as once daily monotherapy in stage 1 and 2 hypertension using more stringent criteria than normal to measure BP control.

It also carries few of the side effects associated with typical beta blockers, researchers reported here at 23rd annual scientific meeting of the American Society of Hypertension.

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Approved by the FDA in January and marketed as Bystolic, nebivolol is a vasodilator that maintains cardiac output and increases stroke volume while decreasing peripheral vascular resistance. Its enhancement of endothelial nitric oxide is believed to be responsible for its vasodilator effects.

A traditional criterion for a response to an antihypertensive drug uses a diastolic blood pressure (DBP) reduction of 10 mm Hg or more. This criterion, however, may not adequately reflect BP control because of the biological variability in steady state BP measurements, said Albert A. Carr, MD, of Southern Clinical Research and Management in Augusta, Ga. Because the variability in DBP is as high as 15 mm Hg, defining response using the more stringent criterion of a 15 mm Hg or greater reduction is more clinically relevant.

“If you can show that a particular dose is better than placebo using this criterion, it really works,” Dr. Carr said. “We have been told to use partitions—less than 140/90 mm Hg and less than 130/80 mm Hg for diabetics—but maybe we should say that you need a really big change. When I see someone with left ventricular mass enlargement, if I get their blood pressure controlled by this criterion [a decrease of at least 15 mm Hg], the mass is lower.”

Using data from randomized, controlled clinical trials of nebivolol monotherapy (2.25 to 40 mg/day) in 909 patients with stage 1 or 2 hypertension, 21.2% to 35.5% of those treated experienced a decline in DBP of at least 15 mm Hg in a dose-dependent manner depending on dose. This was significantly superior to the 9.9% response rate among the placebo recipients.

When using an even more stringent criterion to define response—a decline in DBP of at least 20 mm Hg—response rates ranged from 8.4% to 18.1% with nebivolol (depending on dose) compared with only 1.2% with placebo.

In another pooled analysis performed to assess side effects, Alan H. Gradman, MD, of the Western Pennsylvania Hospital in Pittsburgh, and colleagues reported on three multicenter, double-blind, placebo-controlled trials of nebivolol monotherapy in patients with stage 1 or 2 hypertension. In the studies, a total of 2,016 patients were randomized to placebo or once-daily nebivolol (2.25-40 mg).

Fatigue occurred in 3.6% of the nebivolol group and 1.5% of the placebo group. Of the other adverse events most commonly associated with beta blockers, dyspnea occurred in 1.0% of the nebivolol-treated patients vs. 0.5% of the placebo recipients. The incidence of bradycardia was 0.8% with nebivolol vs. 0.5% with placebo. Erectile dysfunction occurred less often with nebivolol compared with placebo (0.6% vs. 0.9%, respectively), and depression occurred in 0.3% of the nebivolol group and 0% of the placebo group.

The incidence of discontinuations due to adverse events was low in the nebivolol-treated patients, ranging from 0% to 0.2%.

“Further study is required to determine whether the low rates of typical beta blocker adverse events with nebivolol are the result of this agent’s unique mechanism of action, which couples cardioselectivity with endothelial nitric oxide-dependent vasodilator effects,” Dr. Gradman said.