Prevention of Disease Progression Throughout the Cardiovascular Continuum

Transcription

1 Prevention of Disease Progression Throughout the Cardiovascular Continuum

2 Springer-Verlag Berlin Heidelberg GmbH

3 L.E. RYDEN (ED.) Prevention of Disease Progression Throughout the Cardiovaseular Continuum The Role of Adrenergic P -blockade With 153 Figures and 26 rabies Springer

4 Editor: LARS E. RYDEN Professor of Cardiology Department of Cardiology Karolinska Institute S Stockholm Sweden ISBN CIP data applied for Ryden, Lars E.: Prevention of disease progression throughout the cardiovascular continuum : the role of adrenergic blockade; with 26 tables I Lars E. Ryden. - Berlin; Heidelberg; New York ; Barcelona; Budapest; Hong Kong; London ; Mailand ; Paris; Santa Clara; Singapore; Tokyo: Springer, 2001 ISBN ISBN (ebook) DOI / This work is subject to copyright. Ali rights are reserved, whether the whole or part of the material is concerned, specifically the rigths of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. Springer-Verlag Berlin Heidelberg 2001 Originally published by Springer-Verlag Berlin Heidelberg New York in 2001 Softcover reprint ofthe hardcover Ist edition 2001 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Typesetting: Fotosatz-Service Kiihler GmbH, Wiirzburg Cover design: design & production GmbH, Heidelberg SPIN: /3130/ag

5 Preface It has been known since 1894 that a substance extracted from the adrenal gland, later termed 'adrenaline', exerts a profound effect on the blood vessels, heart and skeletal muscles in a variety of animals. However, it was not until 1950 that the first agent which could antagonise the effects of adrenaline was synthesised. This drug was dichloroisoprenaline, a partial p-adrenergic antagonist, which was shown to inhibit the changes in heart rate and muscle tension produced by adrenaline. A derivative of dichloroisoprenaline, pronethalol, was soon developed, which was tested in anginal patients and found to increase the threshold for exercise before onset of pain. However, after long-term toxicity testing revealed that pronethalol could cause cancer of the thymus gland, it was abandoned in favour of propranolol, which, in 1964, became the first p-adrenergic antagonist on the market. Since the launch of propranolol, many different p-adrenergic agents have been developed, with variations in chemical structure achieving a variety of pharmacological properties. These agents became established as core therapy for hypertension, and coronary artery disease. Later, clinical trials also demonstrated their usefulness in reducing mortality in patients after acute myocardial infarction. Despite their wide therapeutic usage, it is only comparatively recently that the wider benefits of P-blockade have been recognised. When p-adrenergic blockade therapy was in its infancy, these agents were believed to be contraindicated in patients with heart failure, as it was thought that the spontaneous sympathetic activation which occurred during heart failure was necessary to maintain adequate cardiac output in the face of worsening pump failure. However, the possibility that p-adrenergic-blocking drugs might exert favourable effects also in heart failure was raised in 1975 [1], when investigators from Sweden described haemodynamic and clinical benefits following long-term use of p-adrenergic blockers in patients with dilated cardiomyopathy. These benefits were found to disappear on withdrawal of treatment [2]. Furthermore, the survival of patients treated with P-blockers was superior to that seen in historical controls [3]. The first unequivocal demonstration of significant survival benefits with adrenergic blockade was achieved in 1996 with carvedilol in the US Carvedilol Programme [4], demonstrating a 65 % reduction in the risk of mortality compared with standard therapy; a result which was unexpected at the time. Further corroboration of the effectiveness of p-adrenergic blockade in reducing mortality and morbidity in heart failure followed with the Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF) [5] and the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II) [6], both of which demonstrated a 34 % mortality reduction with P-blockade compared with standard therapy. At the time of writing, over 13,000 patients have been evaluated in placebo-controlled

6 VI Preface trials of p-adrenergic blockade in heart failure, revealing a consistent improvement in cardiac function, symptoms and clinical status with this therapy. We now recognise that the benefits of adrenergic blockade extend across the cardiovascular continuum, from hypertension, through left ventricular hypertrophy and ischaemic heart disease, to ventricular dysfunction and heart failure. In particular, the role of agents with p-adrenergic blocking activity in preventing progression within this continuum is becoming appreciated. However, despite the compelling evidence for the effectiveness of p-adrenergic blockade in the management of the cardiovascular continuum, a number of outstanding issues remain, especially with regard to chronic heart failure, the end stage of the cardiovascular disease continuum. It is now more than 25 years since the first reports of the effectiveness of p-adrenergic blockade in heart failure, and yet, only recently, has this therapy begun to be adopted into clinical guidelines [7,8] and be implemented in clinical practice. Even now, adrenergic blockade remains chronically underused, and the dogma of its previous perceived contraindication persists, deterring many physicians from administering this therapy in everyday practice, and depriving many patients of its benefits. Outstanding questions also remain over the effectiveness of adrenergic blockade in different patient populations and in different severities and aetiologies of heart failure. An important unresolved issue is whether the pharmacological differences between different anti-adrenergic agents with P-blocking activity, particularly the additional a-blockade seen with carvedilol, result in different outcomes in clinical practice. This book is intended to provide the reader with an insight into the latest thinking in disease management from hypertension to heart failure and to provide practical advice for use of adrenergic blockade in heart failure in everyday clinical practice. Each of the authors has contributed his individual knowledge and insight into his respective chapter. LARS E. RYDEN Professor of Cardiology, The Karolinska Institute, Stockholm, Sweden References 1. Waagstein F, Hjalmarson A, Varnauskas W et al. Effect of chronic p-adrenergic receptor blockade in congestive cardiomyopathy. Br Heart J 1975; 37: Swedberg K, Hjalmarson A, Waagstein F et al. Adverse effects of p-blockade withdrawal in patients with congestive cardiomyopathy. Br Heart J 1980; 44: Swedberg K, Hjalmarson A, Waagstein F et al. Prolongation of survival in congestive cardiomyopathy by p-receptor blockade. Lancet 1979; 1: Packer M Bristow MR, Cohn IN et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Bngl J Med 1996; 334: The MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT -HF). Lancet 1999; 353: CIBIS-II Investigators. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. Lancet 1999; 353: Packer M, Cohn IN on behalf of the Advisory Council to Improve Outcomes Nationwide in Heart Failure (ACTION-HF). Consensus Recommendations for the Management of Chronic Heart Failure. Am J Cardiol1999; 83 (SuppI2A): 2A-77 A. 8. The Task Force on Heart Failure of the European Society of Cardiology. The treatment of heart failure. Bur Heart J 1997; 18:

7 Table of Contents 1 The Cardiovascular Continuum - Pathophysiology and Targets for Therapy T. UNGER Anti-Adrenergic Therapy in Hypertensive Patients with Concomitant Disease W.T.ABRAHAM The Effects of P-Blockade on the Cardiovascular System - Not All P-Blockers are Created Equal F. H. MESSERLI AND E. GROSSMAN The Role of Multiple Adrenergic Blockade in Coronary Artery Disease and Myocardial Infarction A. LAHIRI Epidemiology and Problems with Diagnosis of Heart Failure J. G. F. CLELAND The Future of the Diagnosis of Left Ventricular Dysfunction and Heart Failure H. J. DARGIE Are All P-Blockers the Same for Heart Failure? Insights from Clinical Trials and Future Research Directions M. B. FOWLER The Therapeutic Role of p-adrenoceptor-blocking Agents in Severe Heart Failure H.KRUM Tolerability of Anti-Adrenergic Treatment of Congestive Heart Failure in Daily Practice H.KRUM Adrenergic Blockade in Heart Failure - Official Guidelines and Practical Recommendations on Optimal Use L.E. RYDEN The Future of Heart Failure Management J.G.P. CLELAND Subject Index

8 List of Contributors WILLIAM T. ABRAHAM Professor of Medicine Chief, Division of Cardiovascular Medicine Co-Director, Gill Heart Institute University of Kentucky College of Medicine L-543 Kentucky Clinic 740 South Limestone Street Lexington, KY , USA JOHN G.F. CLELAND Professor of Cardiology Department of Cardiology University of Hull Castle Hill Hospital Cottingham, Kingston upon Hull HU16 5JQ, UK HENRY J. DARGIE Director of the Clinical Research Initiative in Heart Failure University of Glasgow West Medical Building Glasgow, G 12 8QQ, UK MICHAEL B. FOWLER Professor of Medicine Division of Cardiovascular Medicine Falk Cardiovascular Research Center Stanford University Medical Center Stanford, California, , USA EHUD GROSSMAN Professor, M.D., Internal Medicine D The Chaim Sheba Medical Center Sackler School of Medicine Te1-Hashomer 52621, Israel HENRyKRUM Associate Professor of Medicine Clinical Pharmacology Unit Monash Medical School Alfred Hospital Melbourne, Victoria 3181, Australia AVIJIT LAHIRI Director, Cardiac Research Department Department of Cardiovascular Medicine Northwick Park Hospital, and the Institute of Medical Research Watford Road Harrow, Middlesex HA13UJ, UK FRANZ H. MESSERLI Medical Director, Division of Research Alton Ochsner Medical Foundation 1514 Jefferson Highway New Orleans Louisiana 70121, USA LARS E. RYDEN Professor of Cardiology Department of Cardiology Karolinska Institute S Stockholm, Sweden THOMAS UNGER Director of the Institute of Pharmacology Christian -Albrechts-University of Kiel Hospitalstr Kiel, Germany