ABSTRACT
Guanfacine, an alpha-adrenoceptor agonist, may exhibit distinct dose-related curves for efficacy and adverse effects in the step-2 therapy of essential hypertension. To determine the lowest clinically effective safe dose, 462 newly or previously diagnosed subjects were admitted to a 5-week prerandomization phase at 8 centers. Patients were weaned from any current antihypertensive drugs and placed on 25-mg chlorthalidone, daily, in the morning. At the end of the 5-week weaning period, 362 patients with seated diastolic blood pressures (BPs) between 95 and 114 mm Hg qualified for the 12-week postrandomization phase. Subjects were randomized to receive either an indistinguishable placebo or 0.5, 1, 2 or 3 mg of guanfacine. Chlorthalidone was changed to bedtime administration and taken with the study medications. Guanfacine was started at the lowest dose in all subjects and increased (if scheduled, according to the randomization code) to the next higher dose at biweekly intervals. Of the 362 randomized patients, 278 completed the study. The 1-mg guanfacine dosage produced a 14/13 mm Hg decrease in BP (p less than 0.0125 compared with placebo). Doses of guanfacine at 2 and 3 mg/day were not more effective than the 1 mg/day dose; 0.5 mg/day was not better than placebo. There was an increase in the frequency of side effects possibly or probably associated with 2 and 3 mg/day guanfacine. Only 3.2% of the patients in the 1 mg/day group dropped out of the study because of side effects. We conclude that when added to a diuretic, 1 mg/day guanfacine at bedtime is the lowest safe and therapeutically effective dose.
Subject(s)
Guanidines/therapeutic use , Hypertension/drug therapy , Phenylacetates/therapeutic use , Administration, Oral , Adult , Blood Pressure/drug effects , Chlorthalidone/therapeutic use , Clinical Trials as Topic , Double-Blind Method , Drug Evaluation , Drug Therapy, Combination , Female , Guanfacine , Guanidines/adverse effects , Heart Rate/drug effects , Humans , Male , Middle Aged , Phenylacetates/adverse effects , Random AllocationSubject(s)
Cysts/history , Thyroid Diseases/history , Adult , England , Female , History, 19th Century , HumansABSTRACT
Two fixed-combination drugs commonly used in the step 2 treatment of hypertension, chlorthalidone plus reserpine and hydrochlorothiazide plus methyldopa, were compared in an evaluation of efficacy and adverse reactions. Ninety-one percent of the chlorthalidone-reserpine group achieved diastolic blood pressures of 90 mmHg or lower compared with 55% of the hydrochlorothiazide-methyldopa group. The incidence of adverse reactions in the chlorthalidone-reserpine group was 31% compared with an incidence of 64% in the hydrochlorothiazide-methyldopa group.
