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Guanfacine, an alpha 2 adrenoceptor agonist, was compared with prazosin hydrochloride for the treatment of patients with mild to moderate essential hypertension in an 8-week, double-blind, randomized, parallel evaluation to determine efficacy and safety. The study consisted of a 2-week screening/weaning period (phase I), a 3-week treatment period with chlorthalidone 25 mg every morning (phase II), and an 8-week double-blind treatment period with diuretic plus prazosin or guanfacine (phase III). Those who had an average seated diastolic blood pressure (BP) of 95 to 114 mm Hg at the end of the phase II period were eligible to enter the phase III period and were randomly assigned to chlorthalidone plus either guanfacine, 1 mg every night, or prazosin, 1 mg three times a day. Of the 102 patients who were randomly assigned to guanfacine or prazosin, 80% completed the entire study. Guanfacine and prazosin appeared to be equally effective and reduced seated as well as standing diastolic and systolic BP. The mean seated systolic and diastolic BP were reduced 11/9 mm Hg by guanfacine and 11/10 mm Hg by prazosin. The mean reduction in seated pulse was 3 beats/minute for guanfacine and no change with prazosin. Similar changes occurred in the standing position. Very few adverse effects were reported during the study. Adverse effects with an incidence of 5% or greater for either drug group were dizziness (6% guanfacine, 8% prazosin), xerostomia (6% guanfacine, 2% prazosin), and somnolence (0% guanfacine, 6% prazosin). Three patients (6%) in the prazosin group experienced symptoms of orthostasis requiring premature discontinuation of the drug and termination from the study.

Guanfacine, an alpha-2 adrenoceptor agonist, was compared with methyldopa as step-2 therapy for patients with mild-to-moderate essential hypertension in a 12-week, double-blind, randomized, parallel evaluation of efficacy and safety. The study consisted of a 2-week screening/weaning period (phase I), a 3-week treatment period with a diuretic (phase II), and a 12-week treatment period with a diuretic plus methyldopa or guanfacine (phase III). Patients were weaned from prior anti-hypertensive medication during the screening/weaning period and began receiving chlorthalidone 25 mg every morning. Patients received only 25 mg of chlorthalidone each morning during the phase II period. Those who had an average seated diastolic blood pressure (BP) of 95-114 mm Hg at the end of the phase II period were eligible to enter the phase III period and were randomly assigned to chlorthalidone plus guanfacine, 1 mg every night, or methyldopa, 250 mg tid. Seated and standing systolic and diastolic BP and pulses were measured biweekly for 12 weeks after randomization. Of the 112 patients who were randomly assigned to guanfacine or methyldopa, 87% completed the entire study. The mean seated systolic and diastolic BP were reduced 13/13 mm Hg by guanfacine administration and 15/13 mm Hg by methyldopa administration. No significant changes in seated pulse were seen in either group. Similar changes occurred in the standing position. Very few adverse effects were reported during the study, the most prevalent side effect was xerostomia (13% guanfacine, 9% methyldopa). No significant differences were observed between treatment groups for the incidence of cardiac arrhythmias after methyldopa or guanfacine administration was stopped.(ABSTRACT TRUNCATED AT 250 WORDS)

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