To test the antihypertensive and metabolic effects of lisinopril, 10 mg/d (L); hydrochlorothiazide, 12.5 and 25 mg/d (H12.5 and H25); and its combination with lisinopril (L/H12.5 and L/H25) against placebo in patients with mild to moderate (stage I and stage II) hypertension.
Multicenter, double-blind, placebo-controlled outpatient study of 12 weeks' duration.
After 4 weeks of single-blind placebo treatment, 505 patients whose sitting diastolic blood pressure was 100 to 114 mm Hg were randomized into the study—467 patients completed it (placebo, 71; L, 80; H12.5, 79; H25, 77; L/H12.5, 79; and L/H25, 81). The patients were seen in the clinic every 2 weeks, where measurements of their sitting and upright blood pressure and heart rate were taken 24±2 hours after drug administration. Complete blood cell counts with differential cell counts, blood chemistry studies, urinalyses, and electrocardiograms were done at baseline and during the study. Roentgenograms were done once at baseline.
Compared with placebo, all drug regimens decreased sitting and upright blood pressure (P<.001) and had no effect on sitting and upright heart rate. The greatest effect was obtained with the combinations of L/H12.5 and L/H25. There was no difference between L/H12.5 and L/H25 or between H12.5 and H25. There were no serious clinical side effects except cough, which was slightly higher with L, L/H12.5, and L/H25. The only metabolic side effects were in serum potassium level, which was lower with H25 (P<.01), and serum glucose level, which was higher with H25 and L/H25 (P<.01).
The data suggest that (1) monotherapy of hypertension with L, H12.5, H25, L/H12.5, and L/H25 was effective and well tolerated; (2) the best results were achieved with L/H12.5 and L/H25; (3) lower doses of hydrochlorothiazide either alone or in combination with lisinopril were equipotent with higher doses and were free of metabolic side effects.(Arch Intern Med. 1994;154:737-743)