EFFICACY AND SAFETY OF FOSINOPRIL HYDROCHLOROTHIAZIDE COMBINATIONS ONAMBULATORY BLOOD-PRESSURE PROFILES IN HYPERTENSION/

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 take n once daily versus placebo in patients with mild-to-moderate hyperten sion. In two methodologically identical studies, the antihypertensive effects were evaluated by 24-h ABPM and by seated office diastolic (DB P) and systolic (SBP) blood pressures. After a 4- or 5-week placebo wa shout, 79 patients received randomized, double-blind treatment for 8 w eeks 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 wi th 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 A BPM were significantly different from placebo for both doses (SBP/DBP with 10/12.5 mg, -18.2/-10.1 mm Hg, P less than or equal to .001; SBP/ DBP with 20/12.5 mg, -22.9/-11.2 mm Hg, P less than or equal to .001); whereas ambulatory SBP and DBP in the placebo group were virtually un changed. Although the antihypertensive effect of the higher Fos/HCTZ d ose 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 dos es over these two independent studies. This difference in blood pressu re lowering was not reproduced by the office blood pressure readings. Both dose combinations of Fos/HCTZ produced significantly greater redu ctions 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 less than or equal to .01). Based on the results obtained in these trials, both dose combinations of Fos/HCTZ t aken once daily were safe and effective in the management of patients with mild-to-moderate hypertension. Twenty-four-hour ABPM detected wha t appears to be an enhanced blood pressure reduction with the higher F os/HCTZ dose combination (20/12.5 mg) at peak and trough, which was no t reproduced by trough office blood pressure measurements, suggesting greater sensitivity of 24-h ABPM for evaluating antihypertensive effec ts.