Double-blind comparison of doxazosin, nadolol, and placebo in patients with mild-to-moderate hypertension

Doxazosin, an alpha1-adrenergic receptor antagonist, is a new once-a-day antihypertensive agent. In a multicenter, double-blind study, we compared doxazosin to the beta-adrenergic antagonist nadolol and to placebo. Ambulatory adults were eligible if diastolic blood pressure remained between 91 and 114 mmHg during a four-week single-blind placebo phase. Eligible subjects were randomized to receive either doxazosin, nadolol, or placebo. Medication was dispensed by a double-dummy technique, and dosage could be titrated to achieve goal blood pressure. Subjects were evaluated biweekly for the ten weeks of treatment. Subjects who completed the double-blind study were eligible to continue in a one-year open-label study. One hundred eighteen subjects completed the double-blind protocol. Blood pressure decreased to an equivalent degree in both doxazosin-treated and nadolol-treated subjects. Standing systolic blood pressure decreased from 150 ± 18 mmHg (±SD) to 141 ± 20 mmHg in the doxazosin-treated subjects (P ≤ 0.0005; mean decrease of 9.3 ± 11 mmHg), and from 151 ± 16 mmHg to 142 ± 19 mmHg in the nadolol-treated subjects (P ≤ 0.0005; mean decrease of 8.8 ± 15 mmHg). Diastolic blood pressure decreased from 102 ± 6 mmHg to 94 ± 9 mmHg in the doxazosin-treated subjects (P ≤ 0.0005; mean decrease of 8.4 ± 7 mmHg), and from 101 ± 77 mmHg to 93 ± 8 mmHg in nadolol-treated subjects (P ≤ 0.0005; mean decrease of 8.3 ± mmHg). Placebo-treated subjects also experienced a significant decrease in systolic and diastolic blood pressure, but of smaller magnitude. Blood pressure lowering effects of doxazosin and nadolol persisted during the one-year open-label study. During ten weeks of treatment, serum triglyceride and cholesterol levels increased significantly in nadolol-treated subjects, but did not change in either doxazosin- or placebo-treated subjects. We conclude that doxazosin is equal in efficacy to nadolol, when these agents are used as monotherapy for the treatment of mild-to-moderate essential hypertension. In contrast to nadolol, doxazosin does not have adverse effects on serum lipids.

Duke Scholars

Author Laura Pat Svetkey Medicine, Nephrology