A dose-response analysis of candesartan-hydrochlorothiazide combination therapy in patients with hypertension

AIM: To describe the antihypertensive dose-response of combination therapy with candesartan and hydrochlorothiazide (HCT). PATIENTS AND METHODS: Data from 4632 men and women (sex ratio 1:1, mean age 54 years) with mild to moderate hypertension, who participated in one of seven randomized, double-blind, placebo-controlled studies with candesartan-HCT for 8-12 weeks, were entered in a common database. The daily dose of candesartan ranged from 2 to 32 mg, and that of HCT from 6.25 to 25mg. An E(max) model was used to describe the placebo-adjusted dose-response surface for systolic and diastolic blood pressure (BP) reductions. RESULTS: The BP reduction increased with increasing doses of candesartan and HCT, ranging from 5.9 to 17.4 mmHg systolic, and from 2.8 to 10.2 mmHg diastolic with combination therapy. As these figures represent pure drug effects, the effect observed in placebo treated patients (mean reduction 6.0/5.6 mmHg) should be added to estimate the average BP reduction in the usual clinical setting. The reduction with candesartan-HCT represented fully additive contributions of the components. CONCLUSION: The effect of candesartan-HCT is dose-related over a wide range of doses, and the effects of the components are fully additive. This analysis provides guidance for dosing.