Comparison of Nebivolol Monotherapy Versus Nebivolol in Combination With Other Antihypertensive Therapies for the Treatment of Hypertension

Nebivolol is a novel, β₁-adrenergic receptor blocker with vasodilatory properties mediated through the activation of the l-arginine/nitric oxide pathway. Short-term randomized clinical trials have demonstrated that nebivolol has antihypertensive efficacy benefits comparable to other β blockers but with a favorable safety and tolerability profile. The long-term safety and efficacy results of oral nebivolol (5, 10, or 20 mg) 1 time/day, as monotherapy or in combination with other antihypertensive agents, were assessed in a double-blind, multicenter, 9-month extension study of 3 phase III, double-blind, 3-month trials in patients with stage I to II hypertension (mean sitting diastolic blood pressures [BPs] ≥95 and ≤109 mm Hg). Patients were eligible for entry if they had completed 1 of 3 feeder trials of nebivolol monotherapy (1.25 to 40 mg) 1 time/day. Dose titration and use of additional antihypertensive agents were used to achieve a diastolic BP goal of <90 mm Hg. The primary efficacy end point was change in diastolic BP at trough compared with baseline of the feeder study. Of the 845 patients entering this study, 607 patients (72%) were receiving nebivolol monotherapy, 206 patients (24%) were taking nebivolol plus diuretic, 21 patients (2%) were taking nebivolol plus calcium channel blocker, and 11 patients (1%) were taking nebivolol plus other antihypertensive medication at study end. Patients receiving nebivolol monotherapy had decreases in diastolic and systolic BPs of 15.0 and 14.8 mm Hg, respectively. More than 78% of patients were responders to nebivolol monotherapy, and 65% were responders to combination with a diuretic. Overall incidence of adverse events in the extension study was comparable to that seen in the feeder studies and decreased over time. In conclusion, the results demonstrate that nebivolol is a safe and effective antihypertensive therapy that provides long-term BP-lowering effects with a favorable tolerability profile.