Comparison of antihypertensive effects of an angiotensin-converting enzyme inhibitor, a calcium antagonist and a diuretic in patients with hypertension not controlled by angiotensin receptor blocker monotherapy.
OBJECTIVE
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.


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.


RESULTS
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.


CONCLUSIONS
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.
Stergiou
George S
GS
Hypertension Centre, Third University Department of Medicine, Sotiria Hospital, Athens, Greece. gstergi@med.uoa.gr
Makris
Thomas
T
Papavasiliou
Maria
M
Efstathiou
Stamatis
S
Manolis
Athanasios
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001552:Benzazepines / Q000008:administration & dosage*; D018660:Blood Pressure Monitoring, Ambulatory; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D002752:Chlorthalidone / Q000008:administration & dosage; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000068756:Valsartan
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001552:Benzazepines; D002121:Calcium Channel Blockers; D004232:Diuretics; D013777:Tetrazoles; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine; D002752:Chlorthalidone; C044946:benazepril