Antihypertensive efficacy of guanfacine and methyldopa in patients with mild to moderate essential hypertension

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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