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      Usual ACE Inhibitor Therapy in CKD Patients Is Associated with Lower Plasma Aldosterone Levels than Usual Angiotensin Receptor Blocker Therapy

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          Abstract

          Background: Attenuating aldosterone (ALDO) effects may be important in slowing kidney and cardiovascular disease progression. This study tested whether ACE inhibitor (I) therapy achieves lower plasma (p) ALDO levels than angiotensin receptor blocker (ARB) therapy when they are used under usual clinical conditions in chronic kidney disease (CKD) patients. Methods: Consecutive CKD patients (n = 123) were studied. They were clinically stable and receiving either ACEI (n = 77) or ARB (n = 46) (physician’s choice) for ≧3 months. Results: Mean pALDO in the ACEI cohort was 7.8 ± 5.7 (SD) ng/dl compared to 12.3 ± 9.8 ng/dl in the ARB cohort (p = 0.0018, normal ambulatory pALDO 9.4–33.8 ng/dl). The pALDO difference was not explained by differences in age, sex, race, body weight, diagnosis of diabetes; the use of β-blockers, calcium channel blockers or diuretic; systolic or diastolic blood pressure; plasma renin, serum creatinine, sodium, potassium, or bicarbonate levels; 24-hour urine potassium, sodium, urea or protein excretion; or ACEI or ARB dose. Conclusions: Mean pALDO is about 60% higher with ARB therapy than ACEI therapy when these drugs are customarily used in CKD patients. This difference could be clinically important with regard to kidney and cardiovascular protection.

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          Most cited references 34

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          Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy.

          Few studies have directly compared the renoprotective effects of angiotensin II-receptor blockers and angiotensin-converting-enzyme (ACE) inhibitors in persons with type 2 diabetes. In this prospective, multicenter, double-blind, five-year study, we randomly assigned 250 subjects with type 2 diabetes and early nephropathy to receive either the angiotensin II-receptor blocker telmisartan (80 mg daily, in 120 subjects) or the ACE inhibitor enalapril (20 mg daily, in 130 subjects). The primary end point was the change in the glomerular filtration rate (determined by measuring the plasma clearance of iohexol) between the baseline value and the last available value during the five-year treatment period. Secondary end points included the annual changes in the glomerular filtration rate, serum creatinine level, urinary albumin excretion, and blood pressure; the rates of end-stage renal disease and cardiovascular events; and the rate of death from all causes. After five years, the change in the glomerular filtration rate was -17.5 ml per minute per 1.73 m2 (where the minus sign denotes a decrement) in the telmisartan-treated subjects, as compared with -15.0 ml per minute per 1.73 m2 in the enalapril-treated subjects; the treatment difference was thus -2.6 ml per minute per 1.73 m2 (95 percent confidence interval, -7.1 to 2.0 ml per minute per 1.73 m2)[corrected] The lower boundary of the confidence interval, in favor of enalapril, was greater than the predefined margin of -10.0 ml per minute per 1.73 m2, indicating that telmisartan was not inferior to enalapril. The effects of the two agents on the secondary end points were not significantly different after five years. Telmisartan is not inferior to enalapril in providing long-term renoprotection in persons with type 2 diabetes. These findings do not necessarily apply to persons with more advanced nephropathy, but they support the clinical equivalence of angiotensin II-receptor blockers and ACE inhibitors in persons with conditions that place them at high risk for cardiovascular events. Copyright 2004 Massachusetts Medical Society.
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            Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial.

            Present angiotensin-converting-enzyme inhibitor treatment fails to prevent progression of non-diabetic renal disease. We aimed to assess the efficacy and safety of combined treatment of angiotensin-converting-enzyme inhibitor and angiotensin-II receptor blocker, and monotherapy of each drug at its maximum dose, in patients with non-diabetic renal disease. 336 patients with non-diabetic renal disease were enrolled from one renal outpatient department in Japan. After screening and an 18-week run-in period, 263 patients were randomly assigned angiotensin-II receptor blocker (losartan, 100 mg daily), angiotensin-converting-enzyme inhibitor (trandolapril, 3 mg daily), or a combination of both drugs at equivalent doses. Survival analysis was done to compare the effects of each regimen on the combined primary endpoint of time to doubling of serum creatinine concentration or end-stage renal disease. Analysis was by intention to treat. Seven patients discontinued or were otherwise lost to follow-up. Ten (11%) of 85 patients on combination treatment reached the combined primary endpoint compared with 20 (23%) of 85 on trandolapril alone (hazard ratio 0.38, 95% CI 0.18-0.63, p=0.018) and 20 (23%) of 86 on losartan alone (0.40, 0.17-0.69, p=0.016). Covariates affecting renal survival were combination treatment (hazard ratio 0.38, 95% CI 0.18-0.63, p=0.011), age (1.30, 1.03-2.29, p=0.009), baseline renal function (1.80, 1.02-2.99, p=0.021), change in daily urinary protein excretion rate (0.58, 0.24-0.88, p=0.022), use of diuretics (0.80, 0.30-0.94, p=0.043), and antiproteinuric response to trandolapril (0.81, 0.21-0.91, p=0.039). Frequency of side-effects with combination treatment was the same as with trandolapril alone. Combination treatment safely retards progression of non-diabetic renal disease compared with monotherapy. However, since some patients reached the combined primary endpoint on combined treatment, further strategies for complete management of progressive non-diabetic renal disease need to be researched.
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              Angiotensin receptor blockers may increase risk of myocardial infarction: unraveling the ARB-MI paradox.

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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2007
                September 2007
                19 July 2007
                : 30
                : 5
                : 299-305
                Affiliations
                Departments of aInternal Medicine and bStatistics, The Ohio State University, Columbus, Ohio, USA
                Article
                106021 Kidney Blood Press Res 2007;30:299–305
                10.1159/000106021
                17641546
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, Tables: 1, References: 41, Pages: 7
                Categories
                Original Paper

                Cardiovascular Medicine, Nephrology

                ACE inhibitor, Angiotensin receptor blocker, Renal protection

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