Treatment of ambulatory hypertensives with nebivolol or hydrochlorothiazide alone and in combination. A randomized, double-blind, placebo-controlled, factorial-design trial.

This placebo-controlled multifactorial design trial assessed the antihypertensive efficacy of nebivolol, a novel cardioselective beta 1-blocker with vasodilating properties, and hydrochlorothiazide monotherapy and in combination. After a 4-week placebo period, 240 white patients with a mean daytime ambulatory blood pressure of > or = 90 mm Hg were randomized to receive either placebo, nebivolol (1, 5, or 10 mg), hydrochlorothiazide (12.5 or 25 mg), or one of the six possible combinations of nebivolol and hydrochlorothiazide for 12 weeks. A dose-related reduction in clinic and ambulatory blood pressure was demonstrated for each drug as monotherapy and for the two drugs in combination. Nebivolol, 5- and 10-mg doses, showed a larger effect than hydrochlorothiazide doses on clinic blood pressure and over the 24-h interval. Moreover, the combination doses had substantial antihypertensive effects that were sustained over the entire 24-h profile with a greater effect observed with the higher dose combinations. The reduction in ambulatory blood pressure was further substantiated by the reduction of blood pressure loads (% of BP > 140/90 mm Hg awake and >; 120/80 mm Hg asleep) to as low as 11.5% with 10 mg of nebivolol combined with 25 mg of hydrochlorothiazide. Nebivolol and hydrochlorothiazide were well tolerated. We provided evidence that nebivolol, given as monotherapy or in combination with low dose of hydrochlorothiazide, is effective in reducing clinic and 24-h ambulatory blood pressure in patients with ambulatory hypertension. The results provided further evidence for the use of ambulatory blood pressure monitoring and factorial designs when investigating new antihypertensive agents.

RCT Entities:   Population Interventions Outcomes