To compare the additional antihypertensive effects of an angiotensin-converting enzyme inhibitor (ACEI), a dihydropyridine calcium antagonist and a diuretic in patients whose hypertension is not controlled by full-dose angiotensin receptor blocker (ARB) monotherapy.
Design and methods
Individuals with an ambulatory blood pressure (ABP) that was not controlled by valsartan 160 mg once daily were allocated randomly to two groups: those in group A (n = 35) were assigned randomly to treatment with benazepril 20 mg once daily or chlorthalidone 12.5 mg once daily, whereas patients in group B (n = 29) were assigned randomly to benazepril 20 mg once daily or amlodipine 5 mg once daily. All individuals continued to receive background valsartan 160 mg once daily. After 5 weeks, patients crossed over to the alternative valsartan-based combination treatment of each group for a second 5-week period. Twenty-four-hour ABP monitoring was performed before the random allocation to groups and at the end of each randomized combination pharmacotherapy period.
Sixty-four individuals completed the study: 32 men and 32 women (mean ± SD age 48.2 ± 7.9 years, average 24-h ABP on valsartan monotherapy 143.4 ± 12.6/87.7 ± 7.8 mmHg). Significant additional antihypertensive effects on the average 24-h ABP were obtained with benazepril (8.6 ± 8.8/6.3 ± 6.7 mmHg), amlodipine (15.2 ± 12.9/9.9 ± 6.8 mmHg) and chlorthalidone (13.5 ± 11.6/9.5 ± 7.7 mmHg) (P < 0.001 for all additional antihypertensive effects). The additional effects of amlodipine and chlorthalidone added to valsartan were approximately 6/3.5 mmHg (P < 0.05) greater than that of benazepril.
In patients in whom hypertension was not controlled by full-dose ARB monotherapy, a diuretic, a calcium antagonist or an ACE inhibitor provided significant additional antihypertensive effect. The antihypertensive effects of the ARB–diuretic and the ARB–calcium antagonist combinations were superior to that of the ARB–ACE inhibitor combination.