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      Effect of candesartan cilexetil on diabetic and non-diabetic hypertensive patients: meta-analysis of five randomized double-blind clinical trials

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          Abstract

          Objective

          To study the effect of candesartan cilexetil (CC) in the management of blood pressure (BP) in diabetic and non-diabetic hypertensive patients.

          Methods

          A selection of five randomized double-blind clinical trials in which patients were treated for hypertension with CC was analyzed. All of these were similar in design: i) a 4-week placebo run-in period, ii) a 4-to 6-week period (V1) with CC 8 mg once daily (od), after which the dosage was doubled if BP was not normalized (BP >140/90 or BP >130/80 mmHg in diabetes), and iii) a 4- to 6-week period (V2) with CC 8 or 16 mg od. Efficacy was measured at V1 and V2.

          Results

          702 patients were screened. The population consisted of 397 males (56.6%) with a mean age of 60 ± 11 years, with 153 diabetic (21.8%) and 549 non-diabetic (78.2%) patients. At baseline, mean BP values were 160/94/65 mmHg for SPB, DBP, and pulse pressure (PP) respectively, with differences between diabetic and non-diabetic patients. SBP, DBP, and PP values showed a significant reduction at V1 (p < 0.001) and V2 (p < 0.001) compared with baseline for all hypertensive patients. Mean changes at V2 in SBP and PP values were higher in diabetic than non-diabetic patients (p < 0.001), and to a lesser degree on DBP values (p = 0.034).

          Conclusions

          CC was effective in lowering BP in diabetic and non-diabetic hypertensive patients. CC is a promising therapy to manage hypertensive diabetic patients, as demonstrated by the significant BP reduction.

          Short abstract

          The effect of candesartan cilexetil (CC) on controlling blood pressure (BP) in hypertensive diabetic and non-diabetic patients was analyzed. Five randomized double-blind trials were pooled treating hypertension by CC (n = 702), including 153 diabetic (21.8%) and 549 non-diabetic (78.2%) patients. After treatment with CC (8–16 mg), significant reductions in SBP, DBP, and pulse pressure (PP) values were observed after 4–6 weeks (p < 0.001) and after 8–12 weeks (p < 0.001) compared with baseline for all hypertensive patients. Mean BP reductions after 8–12 weeks were higher in diabetic patients than non-diabetic (p < 0.001). CC is a promising therapy to treat hypertensive patients, both diabetic and non-diabetic.

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          Most cited references37

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          The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes.

          Microalbuminuria and hypertension are risk factors for diabetic nephropathy. Blockade of the renin-angiotensin system slows the progression to diabetic nephropathy in patients with type 1 diabetes, but similar data are lacking for hypertensive patients with type 2 diabetes. We evaluated the renoprotective effect of the angiotensin-II-receptor antagonist irbesartan in hypertensive patients with type 2 diabetes and microalbuminuria. A total of 590 hypertensive patients with type 2 diabetes and microalbuminuria were enrolled in this multinational, randomized, double-blind, placebo-controlled study of irbesartan, at a dose of either 150 mg daily or 300 mg daily, and were followed for two years. The primary outcome was the time to the onset of diabetic nephropathy, defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was greater than 200 microg per minute and at least 30 percent higher than the base-line level. The base-line characteristics in the three groups were similar. Ten of the 194 patients in the 300-mg group (5.2 percent) and 19 of the 195 patients in the 150-mg group (9.7 percent) reached the primary end point, as compared with 30 of the 201 patients in the placebo group (14.9 percent) (hazard ratios, 0.30 [95 percent confidence interval, 0.14 to 0.61; P< 0.001] and 0.61 [95 percent confidence interval, 0.34 to 1.08; P=0.081 for the two irbesartan groups, respectively). The average blood pressure during the course of the study was 144/83 mm Hg in the placebo group, 143/83 mm Hg in the 150-mg group, and 141/83 mm Hg in the 300-mg group (P=0.004 for the comparison of systolic blood pressure between the placebo group and the combined irbesartan groups). Serious adverse events were less frequent among the patients treated with irbesartan (P=0.02). Irbesartan is renoprotective independently of its blood-pressure-lowering effect in patients with type 2 diabetes and microalbuminuria.
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            Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial.

            To assess predictors of CVD mortality among men with and without diabetes and to assess the independent effect of diabetes on the risk of CVD death. Participants in this cohort study were screened from 1973 to 1975; vital status has been ascertained over an average of 12 yr of follow-up (range 11-13 yr). Participants were 347,978 men aged 35-57 yr, screened in 20 centers for MRFIT. The outcome measure was CVD mortality. Among 5163 men who reported taking medication for diabetes, 1092 deaths (603 CVD deaths) occurred in an average of 12 yr of follow-up. Among 342,815 men not taking medication for diabetes, 20,867 deaths were identified, 8965 ascribed to CVD. Absolute risk of CVD death was much higher for diabetic than nondiabetic men of every age stratum, ethnic background, and risk factor level--overall three times higher, with adjustment for age, race, income, serum cholesterol level, sBP, and reported number of cigarettes/day (P < 0.0001). For men both with and without diabetes, serum cholesterol level, sBP, and cigarette smoking were significant predictors of CVD mortality. For diabetic men with higher values for each risk factor and their combinations, absolute risk of CVD death increased more steeply than for nondiabetic men, so that absolute excess risk for diabetic men was progressively greater than for nondiabetic men with higher risk factor levels. These findings emphasize the importance of rigorous sustained intervention in people with diabetes to control blood pressure, lower serum cholesterol, and abolish cigarette smoking, and the importance of considering nutritional-hygienic approaches on a mass scale to prevent diabetes.
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              2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension.

              (2003)
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                Author and article information

                Journal
                Vasc Health Risk Manag
                Vascular Health and Risk Management
                Vascular Health and Risk Management
                Dove Medical Press
                1176-6344
                1178-2048
                February 2007
                : 3
                : 1
                : 165-171
                Affiliations
                [1 ]The CardioVascular Institute Paris, France
                [2 ]Laboratoires Takeda Puteaux, France
                Author notes
                Correspondence: Roland Asmar The CardioVascular Institute, 2, rue du Docteur Blanche, 75016 Paris, France Tel +33 1 55 74 66 66 Fax +33 1 55 74 66 65 Email icv@ 123456icv.org
                Article
                1994048
                17583187
                2c08e483-d2d7-4101-a880-93d9c763ca7b
                © 2007 Dove Medical Press Limited. All rights reserved
                History
                Categories
                Original Research

                Cardiovascular Medicine
                blood pressure lowering,antihypertensive diabetes,candesartan cilexetil,angiotensin ii receptor antagonist,hypertension

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