ANTIHYPERTENSIVE EFFECTIVENESS OF LOW-DOSE LISINOPRIL-HYDROCHLOROTHIAZIDE COMBINATION - A LARGE MULTICENTER STUDY

Objective: To test the antihypertensive and metabolic effects of lisin opril, 10 mg/d (L); hydrochlorothiazide, 12.5 and 25 mg/d (H12.5 and H 25), and its combination with lisinopril (L/H12.5 and L/H25) against p lacebo in patients with mild to moderate (stage I and stage II) hypert ension. Design: Multicenter, double-blind, placebo-controlled outpatie nt study of 12 weeks' duration. Patients: After 4 weeks of single-blin d placebo treatment, 505 patients whose sitting diastolic blood pressu re was 100 to 114 mm Hg were randomized into the study-467 patients co mpleted 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 m easurements of their sitting and upright blood pressure and heart rate were taken 24+/-2 hours after drug administration. Complete blood cel l counts with differential cell counts, blood chemistry studies, urina lyses, and electrocardiograms were done at baseline and during the stu dy. Roentgenograms were done once at baseline. Results: Compared with placebo, all drug regimens decreased sitting and upright blood pressur e (P<.001) and had no effect on sitting and upright heart rate. The gr eatest effect was obtained with the combinations of L/H12.5 and L//25. There was no difference between L/H12.5 and L/H25 or between H12.5 an d H25. There were no serious clinical side effects except cough, which was slightly higher with 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 ). Conclusions: The data suggest that (1) monotherapy of hypertension with L, H12.5, H25, L/H12.5, and L/H25 was effective and well tolerate d; (2) the best results were achieved with L/H12.5 and L/H25; (3) lowe r doses of hydrochlorothiazide either alone or in combination with lis inopril were equipotent with higher doses and were free of metabolic s ide effects.