Valsartan alone or with a diuretic or ACE inhibitor as treatment for African American hypertensives: relation to salt intake.
Previous clinical trials have demonstrated the important influence of ethnicity and dietary salt on the antihypertensive efficacy of drugs that block the renin angiotensin system. Angiotensin II receptor blockers are a new therapeutic entity that have not been widely studied in African American hypertensives, either alone, or in combination with other therapies such as diuretics or angiotensin converting enzyme inhibitors. We performed a pilot, prospective, open label, randomized design clinical trial to evaluate the effects of the angiotensin II receptor blocker valsartan (160 mg once a day) on systolic and diastolic blood pressure in hypertensive African Americans (n = 88) on a low salt (100 mEq Na+/day) for 2 weeks and the same diet supplemented by 100 mEq Na+ for 4 weeks. After this evaluation, while continuing the Na+ supplementation, patients were randomized to valsartan 320 mg/day (n = 28), or the addition of hydrochlorothiazide (HCTZ) 12.5 mg/day (n = 30), or benazepril 20 mg/day to the valsartan 160 mg/day for an additional 6 weeks. Valsartan (160 mg/day) lowered blood pressure significantly in African American patients on both low salt (-6.4/-4.8 mm Hg: P < .001) and a high salt diet (-4.9/-3.8 mm Hg: P = .01). The high salt diet attenuated the antihypertensive effect slightly (1.6/1.3 mm Hg, P = not significant). When comparing the efficacy of the three randomized therapeutic regimens while on the Na+ supplement, the valsartan 160 mg/HCTZ 12.5 mg was the most effective therapy with an incremental reduction in blood pressure of -10.5/-6.9 mm Hg (P < .01), compared to valsartan 160 mg/day alone. Doubling the dose of valsartan to 320 mg incrementally lowered blood pressure by -3.8/-3.3 mm Hg (P = not significant). The least effective approach was adding benazepril 20 mg/day to valsartan 160 mg/day with no incremental reduction in systolic blood pressure and diastolic blood pressure reduction of only 1.7 mm Hg (P = not significant). We conclude that in our open label pilot study, the antihypertensive activity of valsartan is not significantly attenuated by supplemented salt diet in hypertensive African Americans. Moreover, adding a low dose of HCTZ appears to be the most effective strategy in enhancing the antihypertensive activity of this angiotensin II receptor blocker in contrast to either doubling the dose or adding an angiotensin converting enzyme inhibitor.
Weir
M R
MR
Department of Medicine, University of Maryland School of Medicine, Baltimore, USA. mweir@medicine.umaryland.edu
Smith
D H
DH
Neutel
J M
JM
Bedigian
M P
MP
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001552:Benzazepines / Q000008:administration & dosage*; D044383:Black People; D004232:Diuretics; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D006973:Hypertension / Q000188:drug therapy* / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage; D012982:Sodium, Dietary / Q000008:administration & dosage*; D013777:Tetrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D014633:Valine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D000068756:Valsartan; D001741:Black or African American
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001552:Benzazepines; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D012982:Sodium, Dietary; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D000068756:Valsartan; D014633:Valine; C044946:benazepril