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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 32mg, and that of HCT from 6.25 to 25mg. An Emax 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 17.4mmHg systolic, and from 2.8 to 10.2mmHg diastolic with combination therapy. As these figures represent pure drug effects, the effect observed in placebo treated patients (mean reduction 6.0/5.6mmHg) 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. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate blood pressure, renal haemodynamics, hormone secretion and the responses to angiotensin II infusion during candesartan cilexetil (candesartan), losartan potassium (losartan) and valsartan treatment in patients with essential hypertension. In this double-blind, randomized, crossover study, 24 patients (mean blood pressure of 163/97 mmHg), received candesartan 16 mg, losartan 50 mg and valsartan 80 mg once daily (o.d.) for 4 weeks after a placebo run-in period. At the end of each period, angiotensin II (0.5, 1.0 and 1.5 ng/min/kg) was infused 24 h after the previous drug administration. Each dose of angiotensin II was infused for 45 min. Before infusion and at the end of each infusion step, blood pressure and renal haemodynamics were assessed and plasma renin activity and plasma concentrations of angiotensin II and aldosterone were measured. During treatment with candesartan, resting mean arterial pressure (mean ± SEM, 106 ± 2 mmHg) was significantly decreased compared with treatment with losartan (110 ± 2 mmHg) and valsartan (109 ± 2 mmHg). Candesartan inhibited the angiotensin II induced increase in filtration fraction (0.8 ± 0.4%) significantly more than losartan (1.5 ± 0.4%) and valsartan (1.6 ± 0.4%) and reduced the increase in aldosterone secretion (17 ± 5 pg/ml/) significantly more than losartan (74 ± 17 pg/ml/) and valsartan (82 ± 19 pg/ml/). In conclusion, candesartan 16 mg o.d. reduced resting blood pressure significantly more than losartan 50 mg o.d. and valsartan 80 mg o.d. Candesartan almost completely inhibited the exogenous angiotensin II induced renal vasoconstriction, effectively inhibited the increase in filtration fraction and significantly blunted aldosterone secretion compared with losartan and valsartan, indicating a more effective AT[sub 1] receptor blockade with candesartan. [ABSTRACT FROM AUTHOR]

The aim of this study was to test the hypothesis that the angiotensin II type 1 receptor blocker (ARB) candesartan can reduce the risk of stroke in elderly patients with isolated systolic hypertension (ISH).Isolated systolic hypertension is the predominant form of hypertension in the elderly, and stroke is the most common cardiovascular (CV) complication.In the Study on Cognition and Prognosis in the Elderly (SCOPE), 4,964 patients age 70 to 89 years were randomly assigned to double-blind candesartan or placebo with open-label antihypertensive therapy (mostly thiazide diuretics) added as needed to control blood pressure. Of the 4,964 patients, 1,518 had ISH (systolic blood pressure >160 mm Hg and diastolic blood pressure <90 mm Hg). The present study is a predefined subgroup analysis of outcome results in the ISH patients.Of the ISH patients, 754 were randomized to the candesartan group and 764 to the control group. Over the study period, blood pressure was reduced by 22/6 mm Hg in the candesartan group and by 20/5 mm Hg in the control group (difference between treatments 2/1 mm Hg; p = 0.101 and 0.064). A total of 20 fatal/non-fatal strokes occurred in the candesartan group (7.2/1,000 patient-years) and 35 in the control group (12.5/1,000 patient-years); relative risk (RR) was 0.58 (95% confidence interval 0.33 to 1.00), that is, a RR reduction of 42% (p = 0.050 unadjusted, p = 0.049 adjusted for baseline risk). There were no marked or statistically significant differences between the treatment groups in other CV end points or all-cause mortality.In elderly patients with ISH, antihypertensive treatment based on the ARB candesartan resulted in a significant 42% RR reduction in stroke in comparison with other antihypertensive treatment, despite little difference in blood pressure reduction. [Copyright &y& Elsevier]