Step-one antihypertensive therapy: a comparison of a centrally acting agent and a diuretic

The safety and antihypertensive efficacy of guanabenz and hydrochlorothiazide (HCTZ) were compared in a 6-month multicenter, double-blind study involving 147 patients. Average daily dosages of guanabenz varied during the study period from 16 to 31 mg, and mean daily dosages of HCTZ varied from 50 to 75 mg. Mean supine diastolic blood pressure (SDBP) decreased from 100 to 85 mm Hg for 33 guanabenz-treated patients (p less than 0.001) and from 99 to 83 mm Hg for 41 HCTZ-treated patients (p less than 0.001) who completed 6 months of treatment. Clinically significant individual decreases in SDBP were observed for 85% of the patients in both treatment groups at 6 months. Mild side effects, which included dry mouth and drowsiness, were reported more frequently by guanabenz-treated patients than by HCTZ-treated patients (p less than 0.01). Among HCTZ-treated patients, statistically significant mean increases from baseline values were noted for uric acid, serum glutamic oxaloacetic transaminase, carbon dioxide, hemoglobin, and blood urea nitrogen levels, whereas mean decreases were observed for potassium and chloride levels. The only clinically significant change in mean laboratory values for the guanabenz group was a decrease of 16 mg/dl in total serum cholesterol (p less than 0.01). The electrolyte and metabolic disturbances associated with HCTZ treatment may lead to increased cardiovascular risk and thus negate or reduce the benefits of successful blood pressure control. A decrease in serum cholesterol levels and a reduction in blood pressure, however, are effects that have been associated with reduced cardiovascular risk. Thus guanabenz therapy may have a more beneficial effect on overall cardiovascular risk than HCTZ therapy.