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 antih ypertensive efficacy of nebivolol, a novel cardioselective beta(1)-blo cker 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 greater than or equa l to 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 week s. A dose-related reduction in clinic and ambulatory blood pressure wa s demonstrated for each drug as monotherapy and for the two drugs in c ombination. 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 antihyperten sive effects that were sustained over the entire 24-h profile with a g reater effect observed with the higher dose combinations. The reductio n in ambulatory blood pressure was further substantiated by the reduct ion 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 wit h 25 mg of hydrochlorothiazide. Nebivolol and hydrochlorothiazide were well tolerated. We provided evidence that nebivolol, given as monothe rapy or in combination with low dose of hydrochlorothiazide, is effect ive in reducing clinic and 24-h ambulatory blood pressure in patients with ambulatory hypertension. The results provided further evidence fo r the use of ambulatory blood pressure monitoring and factorial design s when investigating new antihypertensive agents.