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. Objective: The goal of this study was to compare the duration of the antihy pertensive 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-wee k 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- four-hour ambulatory blood pressure monitoring was performed before and at the end of each treatment period. Systolic and diastolic blood pressure (SB P 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 (patien t/sequence) nor a period effect was found. Mean (SD) 24-hour SEP decreased from 144 +/- 9 mm Hg to 123 +/- 5 mm Hg with ramipril-HCTz and to 125 +/- 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 adminis tered in the run-in and washout periods (P < 0.05). Although the 2 drugs we re equally effective in reducing 24-hour ambulatory blood pressure, the T/P ratios for captopril-HCTz were lower than those for ramipril-HCTz with res pect to both SEP (50% +/- 14% vs 75% +/- 25%; P < 0.05) and DBP (80% +/- 35 % vs 93% +/- 26%; P < 0.05), as were the smoothness indexes for SEP (1.0 vs 1.7; P < 0.05) and DBP (0.7 vs 7.2; P < 0.05). Conclusion: Although both combinations significantly reduced 24-hour blood pressure, ramipril-HCTz produced a more stable antihypertensive effect and less fluctuation in blood pressure than captopril-HCTz.