The aims of the treatment of heart failure are to improve the quality of life and slow the progression of cardiac disease. Improvement of quality of life is best assessed by questionnaire; progression of the disease is assessed by measuring mortality and morbidity. The agenda for the future is to establish intermediate markers for progression of cardiac disease that can be substituted for morbidity and mortality, and thus improve the efficiency and shorten the follow-up of clinical trials. At present, polypharmacy is required to achieve optimal improvements in quality and duration of life. Furthermore, some drugs may favorably affect one end point and adversely affect the other; for example, beta-blockers may exert adverse short-term effects on quality of life but may slow progression of the disease. Certain inotropic drugs may reduce symptoms but shorten life expectancy. Angiotensin-converting enzyme (ACE) inhibitors have exerted favorable effects on both quality of life and mortality, but the magnitude of these benefits has been disappointingly small. Persistent angiotensin-induced vasoconstriction and endocrine effects, despite ACE inhibition, is one possible explanation. The Valsartan in Heart Failure Trial (Val-HeFT) has been designed to test the efficacy and safety of the AT1 receptor blocker (ARB) valsartan in combination with ACE inhibitors and all other prescribed therapies in patients with heart failure. The study is powered to detect a mortality benefit and should therefore establish the role of ARBs in this patient group. When this trial and other ongoing studies are completed, we will be more able to define the role of ARBs in the treatment of heart failure.

Massie BM, Shah NB: Evolving trends in the epidemiologic factors of heart failure: rationale for preventive strategies and comprehensive disease management. Am Heart J 1997;133:703–712.
Levine TB, Francis GS, Goldsmith SR, Simon AB, Cohn JN: Activity of the sympathetic nervous system and renin-angiotensin system assessed by plasma hormone levels and their relation to hemodynamic abnormalities in congestive heart failure. Am J Cardiol 1982;49:1659–1666.
Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T: Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984;311:819–823.
Cohn JN: Structural basis for heart failure. Ventricular remodeling and its pharmacological inhibition [editorial]. Circulation 1995;91:2504–2507.
Goldman S, Johnson G, Cohn JN, Cintron G, Smith R, Francis G: Mechanism of death in heart failure. The Vasodilator-Heart Failure Trials. The V-HeFT VA Cooperative Studies Group. Circulation 1993;87:VI24–VI31.
Ziesche S, Cobb FR, Cohn JN, Johnson G, Tristani F: Hydralazine and isosorbide dinitrate combination improves exercise tolerance in heart failure. Results from V-HeFT I and V- HeFT II. The V-HeFT VA Cooperative Studies Group. Circulation 1993;87:VI56–VI64.
Rector TS, Kubo SH, Cohn JN: Validity of the Minnesota Living with Heart Failure questionnaire as a measure of therapeutic response to enalapril or placebo. Am Heart J 1993;71:1106–1107.
Cohn JN, Archibald DG, Ziesche S, Franciosa JA, Harston WE, Tristani FE, Dunkman WB, Jacobs W, Francis GS, Flohr KH, Goldman S, Cobb FR, Shah PM, Saunders R, Fletcher RD, Loeb HS, Hughes VC, Baker B: Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med 1986;314:1547–1552.
Luu M, Stevenson WG, Stevenson LW, Baron K, Walden J: Diverse mechanisms of unexpected cardiac arrest in advanced heart failure. Circulation 1989;80:1675–1680.
O’Connell JB, Bristow MR: Economic impact of heart failure in the United States: time for a different approach. J Heart Lung Transplant 1994;13:S107–S112.
The SOLVD Investigators: Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325:293–302.
Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, Shusterman NH: The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med 1996;334:1349–1355.
CIBIS-II investigators: The cardiac insufficiency bisoprolol study II (CIBIS II): a randomised trial. Lancet 1999;353:9–13.
Packer M, Cohn JN: Consensus recommendations for the management of chronic heart failure. Am J Cardiol 1999;83:2A–38A.
Cohn JN, Johnson G, Ziesche S, Cobb F, Francis G, Tristani F, Smith R, Dunkman WB, Loeb H, Wong M, Bhat G, Goldman S, Fletcher RD, Doherty J, Hughes CV, Carson P, Cintron G, Shabetai R, Haakenson C: A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991;325:303–310.
Francis GS, Cohn JN, Johnson G, Rector TS, Goldman S, Simon A, for the V-HeFT VA Cooperative Studies Group: Plasma norepinephrine, plasma renin activity, and congestive heart failure: relations to survival and the effects of therapy in V-HeFT II. Circulation 1993;87(suppl VI):VI40–VI48.
Urata H, Healy B, Stewart RW, Bumpus FM, Husain A: Angiotensin II-forming pathways in normal and failing human hearts. Circ Res 1990;66:883–890.
Okunishi H, Oka Y, Shiota N, Kawamoto T, Song K, Miyazaki M: Marked species-difference in the vascular angiotensin II-forming pathways: humans versus rodents. Jpn J Pharmacol 1993;62:207–210.
Balcells E, Meng QC, Johnson Jr WH, Oparil S, Dell’Italia LJ: Angiotensin II formation from ACE and chymase in human and animal hearts: methods and species considerations. Am J Physiol 1997;273:H1769–H1774.
Nussberger J, Fleck E, Bahrmann H, Delius W, Schultheiss HP, Brunner HR: Dose-related effects of ACE inhibition in man: quinapril in patients with moderate congestive heart failure. The Study Group on Neurohormonal Regulation in Congestive Heart Failure: Lausanne, Switzerland; Berlin, Dusseldorf, Munich, Germany. Eur Heart J 1994;15(suppl D):113–122.
Schunkert H, Ingelfinger JR, Hirsch AT, Pinto Y, Remme WJ, Jacob H, Dzau VJ: Feedback regulation of angiotensin converting enzyme activity and mRNA levels by angiotensin II. Circ Res 1993;72:312–318.
van den Broek SA, de Graeff PA, van Veldhuisen DJ, van Gilst WH, Hillege H, Wesseling H, Lie KI: Clinical and neurohumoral differences between spirapril and captopril in mild to moderate chronic congestive heart failure. J Card Fail 1997;3:165–171.
Kawamura M, Imanashi M, Matsushima Y, Ito K, Hiramori K: Circulating angiotensin II levels under repeated administration of lisinopril in normal subjects. Clin Exp Pharmacol Physiol 1992;19:547–553.
Packer M: Do angiotensin-converting enzyme inhibitors prolong life in patients with heart failure treated in clinical practice? J Am Coll Cardiol 1996;28:1323–1327.
Baruch L, Anand I, Cohen IS, Ziesche S, Judd D, Cohn JN, for the V-HeFT Study Group: Augmented acute and chronic hemodynamic and hormonal effects of an angiotensin blocker added to angiotensin converting enzyme inhibitor therapy in patients with heart failure. Circulation (In press).
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.