Blood pressure response to combination therapy with ramipril or captopril plus hydrochlorothiazide: a randomized, active-controlled, crossover study

Background: Combination therapy is often required to achieve adequate blood pressure control in patients with hypertension. Ob]ective: The goal of this study was to compare the duration of the antihypertensive effects of ramipril 5 mg and captopril 50 mg, each combined with hydrochlorothiazide (HCTz) 25 mg. Methods: This was a randomized, active-controlled, double-blind, crossover study enrolling 22 patients with mild essential hypertension. After a 4-week placebo run-in period, patients were randomized to two 4-week periods of daily treatment with ramipril-HCTz or captopril-HCTz, each period separated by a 4-week washout period, during which placebo was administered. Twenty-fourhour ambulatory blood pressure monitoring was performed before and at the end of each treatment period. Systolic and diastolic blood pressure (SBP and DBP) were recorded, and the trough-to-peak (T/P) ratio and smoothness index (derived from the SDS of all hourly blood pressure changes over the 24 hours following treatment) were calculated. Results: All 22 patients (13 men, 9 women; mean age, 52 + 8 years; office DBP, 95-110 mm Hg) completed the study. Neither a carryover effect (patient/ sequence) nor a period effect was found. Mean (*SD) 24-hour SBP decreased from 144 + 9 mm Hg to 123 + 5 mm Hg with ramipril-HCTz and to 125 5 7 mm Hg with captopril-HCTz; mean 24-hour DBP decreased from 90 + 7 mm Hg to 78 + 6 mm Hg with ramipril-HCTz and to 80 + 5 mm Hg with captopril-HCTz. All differences were statistically significant versus placebo administered in the run-in and washout periods (P < 0.05). Although the 2 drugs were equally effective in reducing 24-hour ambulatory blood pressure, the T/P ratios for captopril-HCTz were lower than those for ramipril-HCTz with respect to both SBP