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      Long-Term Potential of Angiotensin Receptor Blockade for Cardiovascular Protection in Hypertension: The VALUE Trial

      S. Karger AG
      Hypertension, VALUE trial, Left ventricular hypertrophy, Morbidity

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          The recent decrease of cardiovascular mortality in the USA is less pronounced than it has been in the preceding three decades. Elsewhere, cardiovascular mortality decreased and in some countries it increased. Cerebrovascular disease and ischemic heart disease were responsible for 21% of deaths recorded by the World Health Organization in 1990 and 1997, of which hypertension was estimated to be directly responsible for half of these deaths. Apart from blood pressure (BP) elevation, essential hypertension is frequently associated with factors that increase the risk of poor cardiovascular outcomes: insulin resistance/dyslipidemia, elevated angiotensin and norepinephrine, a tendency for hypercoagulability, platelet overactivity, tachycardia, vulnerability to arrhythmias, vascular hypertrophy, endothelial dysfunction, and left ventricular hypertrophy. Excess activation of the renin-angiotensin system, independent of BP elevation, contributes to these abnormalities. To achieve better results in the future, focus must be shifted from BP lowering to recognition of specific effects of drugs on these diverse pathophysiologic aspects of hypertension. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, which is evaluating the effect of valsartan (Diovan<sup>®</sup>) vs. amlodipine, is a milestone in the effort to test whether newer compounds offer a better reduction of the cardiovascular consequences of hypertension, as well as good BP control. The hypothesis is that valsartan by antagonizing the negative effects of angiotensin on smooth muscle cell growth, endothelial function, sympathetic overactivity, and coagulation, may have for the same degree of BP lowering, better protective effects than the leading calcium antagonist amlodipine.

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              Hypertension in the elderly. Implications and generalizability of randomized trials.

              To estimate morbidity and mortality benefits of drug therapy for hypertensive elderly subjects, compare these benefits with effects in younger subjects, and provide a framework for generalizing results derived from trials to actual patients. A literature search using MEDLINE from 1966 to 1993, references from reviews and trial articles, and experts. Randomized trials lasting at least 1 year that evaluated effects of drug treatment on morbidity and mortality outcomes in hypertensive persons. Four independent reviewers appraised protocol characteristics and quality of selected trials. There were 13 trials involving 16,564 elderly persons (age 60 years and older). The prevalence of cardiovascular risk factors, cardiovascular disease, and competing comorbid diseases was lower among trial participants than the general population of hypertensive elderly persons. When the six large high-quality trials were combined, trial results showed 43 subjects (95% confidence interval [CI], 31 to 69) and 61 subjects (95% CI, 39 to 141) needed to be treated for 5 years to prevent one cerebrovascular event and one coronary heart disease event, respectively. Including the other seven trials did not change the results significantly. Only 18 subjects (95% CI, 14 to 25) needed to be treated to prevent one cardiovascular event (cerebrovascular or cardiac). Twelve trials in primarily younger and middle-aged adults involved approximately 33,000 persons. For all outcomes except cardiac mortality, two to four times as many of the younger subjects as the older subjects needed to be treated for 5 years to prevent morbid and mortal events. No significant effect on cardiac mortality was seen among younger subjects, while 78 older subjects (95% CI, 50 to 180) needed to be treated to prevent a fatal cardiac event. Randomized trials demonstrate that treating healthy older persons with hypertension is highly efficacious. Five-year morbidity and mortality benefits derived from trials are greater for older than younger subjects. Extrapolating benefits from trials to individual patients is difficult, but should take into account multiple issues including the patient's risk factors, preexisting cardiovascular disease, and competing comorbid illnesses.

                Author and article information

                S. Karger AG
                August 1999
                06 August 1999
                : 91
                : Suppl 1
                : 8-13
                Division of Hypertension, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Mich., USA
                47282 Cardiology 1999;91(suppl 1):8–13
                © 1999 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: 2, Tables: 1, References: 47, Pages: 6

                General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Left ventricular hypertrophy,Morbidity,VALUE trial,Hypertension


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