COMPARISON OF FOSINOPRIL AND HYDROCHLOROTHIAZIDE IN PATIENTS WITH MILD TO MODERATE HYPERTENSION

Seventeen patients with mild to moderate hypertension, as indicated by a diastolic blood pressure (DPB) of 95-115 mmHg (WHO I), were treated in a randomized, double-blind, parallel study, with either 5 mg of fosinopril, a new phosphinic acid-containing angiotensin converting enzyme (ACE) inhibitor, or 25 mg of hydrochlorothiazide administered orally once daily for 4 weeks after a 4- to 6-week run-in period of placebo. The doses were increased to 10 mg of fosinopril or 50 mg of hydrochlorothiazide if DBP remained above 95 mmHg. The blood pressure (BP) fell from 157 +/- 12/104 +/- 7 mmHg (mean value +/- SD) at the start of the study to 146 +/- 21/97 +/- 8 mmHg (P < 0.02) after 4 weeks, and to 149 +/- 19/97 +/- 7 mmHg (P < 0.02) after 8 weeks of fosinopril treatment (n = 8). In the hydrochlorothiazide-treated patients (n = 9), BP fell from 153 +/- 9/105 +/- 5 mmHg at the start of the study to 140 +/- 11/97 +/- 7 mmHg (P < 0.01) after 4 weeks, and to 131 +/- 11/94 +/- 7 mmHg (P < 0.01) after 8 weeks. After the first dose, DBP fell from 102 to 99 mmHg (NS) in fosinopril-treated patients, and from 105 to 96 mmHg (P < 0.02) in hydrochlorothiazide-treated subjects. Serum active fosinoprilate concentration increased to 5.6 ng ml-1, 25.9 ng ml-1, and 43.8 ng ml-1 after 30, 60 and 120 min, respectively, and remained at a level of 6.6-7.7 ng ml-1 after 4 and 8 weeks, respectively. Serum ACE activity decreased from 21.6 +/- 11.0-mu-mol min-1 l-1 at the start to 9.3 +/- 13.7, 4.4 +/- 4.6, and 2.9 +/- 2.8-mu-mol min-1 l-1 after 30, 60 and 120 min, respectively. No side-effects and no changes in blood counts, electrolytes or kidney function were attributed to fosinopril during the study. Fosinopril is a safe, long-acting antihypertensive drug with a smooth onset of action. Hydrochlorothiazide treatment caused potassium loss and an increase in the levels of uric acid and triglycerides. Diastolic blood pressure decreased to the same extent as a result of treatment with either drug, while systolic blood pressure was better controlled by hydrochlorothiazide.