Lofexidine and clonidine in moderate essential hypertension

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Abstract
The efficacy, safety, and tolerability of lofexidine, a centrally acting imidazoline derivative, were compared to that of clonidine in a randomized double‐blind trial in 28 patients with moderate essential hypertension. The study consisted of a washout phase, a placebo phase, a drug titration phase (0.2 to 1.6 mglday, with hydrochlorothiazide added at 0.4 mg daily for supine and erect diastolic blood pressure above 90 mm Hg), and a maintenance phase lasting 3 mo. During the titration phase supine systolic and diastolic pressures fell in lofexidine patients from 143 ± 4198 ± 3 to 122 ± 3181 ± 2 mm Hg and in clonidine patients from 154 ± 61101 ± 2 to 124 ± 4/81 ± 2 mm Hg (P < 0.01), and erect systolic and diastolic pressures fell in lofexidine patients from 143 ± 31105 ±2 to 116 ± 3185 ± 2 mm Hg and in clonidine patients from 156 ± 6/104 + 2 to 117 ± 4/82 ± 2 mm Hg (P < 0.01). Maximal doses of lofexidine and clonidine in combination with hydrochlorothiazide had equivalent antihypertensive effects, but when the effects of lofexidine and clonidine were compared at each dose level, larger doses of lofexidine were needed to control blood pressure. There was no change in heart rate in lofexidine patients in either the supine or erect position during the titration phase but heart rate fell in the clonidine patients (P < 0.05) over the same period. Dry mouth and drowsiness were reported in both groups but were both less frequent and less severe in the lofexidine group than the clonidine group. Clinical Pharmacology and Therapeutics (1981) 30, 752–757; doi:10.1038/clpt.1981.234

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