Efficacy and Safety of Fosinopril/Hydrochlorothiazide Combinations on Ambulatory Blood Pressure Profiles in Hypertension

Abstract

Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was used to assess the antihypertensive efficacy and safety of the angiotensin converting enzyme (ACE) inhibitor fosinopril (Fos) in combination with hydrochlorothiazide (HCTZ) in doses of 10/12.5 mg and 20/12.5 mg taken once daily versus placebo in patients with mild-to-moderate hypertension. In two methodologically identical studies, the antihypertensive effects were evaluated by 24-h ABPM and by seated office diastolic (DBP) and systolic (SBP) blood pressures. After a 4- or 5-week placebo washout, 79 patients received randomized, double-blind treatment for 8 weeks with either the Fos/HCTZ 10/12.5-mg dose combination (n = 41) or placebo (n = 38), and in the second study, 62 patients were treated with either the Fos/HCTZ 20/12.5-mg dose combination (n = 30) or placebo (n = 32). Changes from baseline in mean 24-h systolic and diastolic ABPM were significantly different from placebo for both doses (SBP/DBP with 10/12.5 mg, -18.2/ -10.1 mm Hg, P <or= .001; SBP/DBP with 20/12.5 mg, -22.9/ -11.2 mm Hg, P <or= .001); whereas ambulatory SBP and DBP in the placebo group were virtually unchanged. Although the antihypertensive effect of the higher Fos/HCTZ dose combination (20/12.5 mg) appeared greater than the lower dose (10/12.5 mg), no attempt was made to make a comparison between the two doses over these two independent studies. This difference in blood pressure lowering was not reproduced by the office blood pressure readings. Both dose combinations of Fos/HCTZ produced significantly greater reductions in the office seated DBP than placebo at all time points tested with a maximum treatment effect (drug effect - placebo effect) of -7.3 mm Hg for the 10/12.5-mg dose and -8.2 mm Hg for the 20/12.5-mg dose after 8 weeks of therapy (P <or= .01). Based on the results obtained in these trials, both dose combinations of Fos/HCTZ taken once daily were safe and effective in the management of patients with mild-to-moderate hypertension. Twenty-four-hour ABPM detected what appears to be an enhanced blood pressure reduction with the higher Fos/HCTZ dose combination (20/12.5 mg) at peak and trough, which was not reproduced by trough office blood pressure measurements, suggesting greater sensitivity of 24-h ABPM for evaluating antihypertensive effects.