Guanfacine as monotherapy for systemic hypertension

Abstract

Three clinical studies examined the effects of guanfacine as monotherapy. Study 1 was a double-blind, randomized, parallel trial with a placebo control with 26 patients with mild essential hypertension treated with 1-mg guanfacine or matching placebo daily at bedtime for 8 weeks. Pretreatment and posttreatment determinations of plasma volume, plasma aldosterone and blood pressure (BP) were made in all 26 patients. There were no significant differences between guanfacine and placebo with regard to changes in plasma volume or plasma aldosterone, but a significant decrease (p = 0.001) in both diastolic and mean BPs was seen with the active drug. No side effects were reported. From this study, it was concluded that guanfacine monotherapy is an effective and well-tolerated initial treatment for mild essential hypertension with no effect on either plasma volume or plasma aldosterone. Study 2 was a double-blind, randomized, parallel clinical study with placebo control with 42 patients with mild essential hypertension treated with either guanfacine (1 mg/day) or matching placebo at bedtime for 8 weeks. Pretreatment and posttreatment evaluations of serum cholesterol, triglycerides, low density lipoproteins, very low density lipoproteins and high density lipoproteins revealed no significant differences between the treatment and the placebo groups. A statistically significant (p <0.0001) decrease in diastolic BP was seen in the guanfacine group compared with those patients who received placebo. Guanfacine monotherapy was again shown to be an effective initial treatment for mild essential hypertension with no adverse influence on serum lipids. In study 3, the efficacy and safety of guanfacine and guanabenz for the initial treatment of mild to moderate essential hypertension were compared, using a double-blind, randomized, parallel protocol. Guanfacine (1 mg/day) was given at bedtime, and placebo was given both at bedtime and in the morning to match the 2-times-a-day dosage schedule of guanabenz (4 mg/day for week 1 and 8 mg/day for the remaining 7 weeks of the study). Endpoint comparison of decreases in BP showed that both drugs were equally effective, but somnolence was observed in twice as many of the guanabenz-treated patients. This study demonstrated the effectiveness of guanfacine and guanabenz as initial treatment of mild to moderate essential hypertension; guanfacine monotherapy offered the advantages of once-a-day dosing and less drowsiness.