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.

A new chronotherapeutic oral drug absorption system for verapamil optimizes blood pressure control in the morning.

A novel verapamil chronotherapeutic oral drug absorption system (CODAS-Verapamil) designed for bedtime dosing and with controlled onset and extended-release properties was evaluated in 257 patients with mild-to-moderate essential hypertension in an 8-week, double-blind, placebo-controlled trial. After bedtime dosing (9 PM to 11 PM, this delivery system delays drug release for 4 to 5 h, and provides the highest concentrations of verapamil between 6 AM and noon. The study results showed that CODAS-verapamil produced its greatest antihypertensive effect during this morning period (6 AM to 12 noon) and also provided effective trough diastolic blood pressure reductions at 200, 300, and 400 mg. Significant trough systolic blood pressure reductions were achieved only with the 300- and 400-mg doses. The nighttime dosing regimen was not associated with excessive blood pressure (BP) reductions during the sleeping hours, when the antihypertensive effect was generally slightly less than that of the 24-h mean reduction. The CODAS-verapamil provides enhanced BP reduction during the morning period when compared with other time intervals of the 24-h dosing period.

A comparative study of atenolol, nifedipine and their combination in the treatment of hypertension.

The antihypertensive effects, as assessed by clinical and ambulatory blood pressure measurement, of nifedipine slow-release (SR), atenolol and the two in combination were evaluated in 28 known hypertensives in a placebo-controlled, double-blind, randomised cross-over trial. Clinical blood pressure was significantly lower on combination therapy (P less than 0.025) than on either agent alone, although all therapeutic agents reduced blood pressure significantly when compared with placebo (P less than 0.01). All ambulatory blood pressure measurements obtained on any therapeutic agent were significantly lower than those obtained on placebo (P less than 0.01). The mean daytime (08h00-17h00) ambulatory blood pressure measurement as well as the percentage of this monitoring period during which patients were hypertensive were significantly lower (P less than 0.01) on combination therapy than on nifedipine SR. A similar pattern was observed for 24-hour ambulatory blood pressure measurements. Headache was the most significant adverse effect. This was most common with nifedipine SR, less common with combination therapy and least common with atenolol. Combination therapy with nifedipine SR and atenolol is therefore a viable therapeutic alternative in the treatment of patients with benign essential hypertension.