Scrip's Complete Guide to Cardiovascular Diseases


Therapeutic


NEW
Providing in-depth information on all the major cardiovascular disease (CVD) areas of hypertension, coronary heart disease, arrhythmia, congestive heart failure and stroke, this extensive report includes:


* R&D information for over 200 drugs currently in development
* Market potential estimates for new and emerging therapies
* Current market figures and sales forecasts to 2002
* Profiles of 19 major players in the CVD treatment market


Scrip's Complete Guide to Cardiovascular Diseases provides you with a comprehensive overview of the CVD market. Volume 1 of the report details the most advanced clinical understanding of CVD. By providing you with the latest market data, and commentary on trends and influences that will shape the CVD drug market, this report allows you to gain a complete understanding of both current and future market status.


Volumes 2-5 cover each disease area separately. Each includes an introduction to the disease area and the latest understanding of the disease process, an in-depth evaluation of drugs on the market and their performance, opportunities for new products and a detailed analysis of products in clinical development. Each volume also has up-to-date trial data and tabulated information on compounds in development, from preclinical to registered.


PUBLISHED: November 1999
REF: BS1030E
PAGES: 500+
PRICE: Complete six-volume set �990/$1,995/�238,000


CONTENTS
LIST OF TABLES
LIST OF FIGURES
EXECUTIVE SUMMARY
METHODOLOGY
ABBREVIATIONS
CLINICAL TRIAL ACRONYMS


CHAPTER 1 INTRODUCTION
1.1 Definition of congestive heart failure
1.1.1 Classification of congestive heart failure
1.2 Diagnosis of congestive heart failure
1.3 Pathophysiology of congestive heart failure
1.3.1 Systolic failure
1.3.2 Diastolic failure
1.3.3 Other pathophysiological changes in congestive heart failure
1.4 Incidence and prevalence of congestive heart failure
1.4.1 Special populations
1.4.1.1 Elderly
1.4.1.2 Sex
1.4.1.3 Racial and ethnic groups
1.5 The economic cost of congestive heart failure
1.6 Risk factors for congestive heart failure
1.6.1 Hypertension
1.6.2 Coronary artery disease/coronary heart disease
1.6.3 Alcohol
1.6.4 Socio-economic status
1.7 Complications associated with congestive heart failure
1.7.1 Ventricular arrhythmia
1.7.2 Atrial fibrillation
1.7.3 Uraemia
1.7.4 Liver dysfunction
1.8 The management of congestive heart failure
1.8.1 Non-pharmacological management
1.8.1.1 Diet
1.8.1.2 Fluid intake
1.8.1.3 Alcohol intake
1.8.1.4 Smoking
1.8.1.5 Exercise
1.8.2 Pharmacological management
1.8.3 Intractable heart failure
1.9 Conclusion

CHAPTER 2 MARKETED DRUGS FOR THE MANAGEMENT OF CONGESTIVE HEART FAILURE
2.1 Introduction
2.2 Diuretics
2.2.1 Thiazide diuretics
2.2.1.1 Bendrofluazide
2.2.1.2 Cyclopenthiazide
2.2.1.3 Hydrochlorothiazide
2.2.2 Thiazide-like diuretics
2.2.2.1 Chlorthalidone
2.2.2.2 Xipamide
2.2.3 Loop diuretics
2.2.3.1 Bumetanide
2.2.3.2 Frusemide
2.2.3.3 Piretanide
2.2.3.4 Torasemide
2.2.4 Potassium-sparing diuretics
2.2.4.1 Spironolactone
2.3 Inotropic agents
2.3.1 Digoxin
2.3.2 Beta-1 adrenoceptor agonists
2.3.2.1 Dobutamine
2.3.3 Dopamine agonists
2.3.3.1 Docarpamine
2.3.3.2 Dopamine
2.3.3.3 Dopexamine
2.3.3.4 Ibopamine
2.3.4 Phosphodiesterase inhibitors
2.3.4.1 Amrinone
2.3.4.2 Enoximone
2.3.4.3 Milrinone
2.3.4.4 Vesnarinone
2.4 ACE inhibitors
2.4.1 Captopril
2.4.2 Cilazapril
2.4.3 Enalapril
2.4.4 Fosinopril
2.4.5 Imidapril
2.4.6 Lisinopril
2.4.7 Perindopril
2.4.8 Quinapril
2.4.9 Ramipril
2.4.10 Trandolapril
2.5 Beta-blockers
2.5.1 Bisoprolol
2.5.2 Carvedilol
2.5.3 Metoprolol
2.6 Vasodilators
2.7 Angiotensin II antagonists
2.7.1 Candesartan
2.7.2 Eprosartan
2.7.3 Irbesartan
2.7.4 Losartan
2.7.5 Valsartan
2.8 Alpha-blockers
2.9 Conclusion

CHAPTER 3 HEART FAILURE DRUGS IN DEVELOPMENT
3.1 Introduction
3.2 ACE inhibitors in development
3.2.1 Quinaprilat
3.2.2 Zofenopril
3.3 Beta-blockers in development
3.3.1 Bucindolol
3.4 Neutral endopeptidase inhibitors
3.4.1 BMS-189921
3.4.2 Ecadotril
3.4.3 Fasidotril
3.4.4 Mixanpril
3.4.5 Sampatrilat
3.4.6 Omapatrilat
3.5 Endothelin antagonists
3.5.1 BMS-193884
3.5.2 Bosentan
3.5.3 LU-135252
3.5.4 TBC-11251
3.6 Natriuretic peptides
3.6.1 Nesiritide
3.6.2 Urodilatin
3.7 Phosphodiesterase inhibitors
3.7.1 IC-351
3.7.2 MCI-154
3.7.3 Toborinone
3.8 Calcium sensitisers
3.8.1 EMD-82571
3.8.2 Levosimendan
3.8.3 MCC-135
3.9 Aldosterone antagonists
3.9.1 Epoxymexrenone
3.10 Cytokine and growth factor inhibitors
3.10.1 Etanercept
3.10.2 Growth factors
3.10.3 CytoTAb
3.11 Vasopressin antagonists
3.11.1 OPC-21268 and OPC-31260
3.11.2 YM-087
3.12 Other agents in development for congestive heart failure
3.12.1 Moxonidine
3.12.2 Colforsin daropate
3.12.3 ST-261
3.12.4 CHF-1035
3.12.5 S-21402
3.12.6 Mildronate
3.13 Conclusion


REFERENCES


LIST OF TABLES
Table M.1 Average exchange rates against the US$, 1996-1998
Table 1.1 New York Heart Association functional classifications of congestive heart failure status
Table 1.2 Drugs for the treatment of congestive heart failure
Table 2.1 Diuretics indicated for congestive heart failure
Table 2.2 Inotropic agents on the market
Table 2.3 ACE inhibitors marketed for the treatment of congestive heart failure
Table 2.4 Beta-blockers on the market
Table 2.5 Coronary vasodilators indicated for congestive heart failure in the UK
Table 3.1 Neutral endopeptidase inhibitors in development
Table 3.2 Endothelin antagonist in development for congestive heart failure therapy
Table 3.3 Phosphodiesterase inhibitors in development for congestive heart failure
Table 3.4 Calcium sensitising agents in development for congestive heart failure

LIST OF FIGURES
Figure 1.1 Prevalence of congestive heart failure by race and sex in the US in 25-74 year olds, 1971-1994
Figure 1.2 Estimated prevalence of congestive heast failure by age and sex in the US,
1988-1994


This volume, Congestive Heart Failure, is part of a series forming Scrip's Complete Guide to Cardiovascular Diseases. The other volumes in this series are:

EXECUTIVE SUMMARY
Although the market for agents specifically aimed at treating congestive heart failure (CHF) is the smallest sector of the cardiovascular drugs market, worth about $23 million in 1998, the bulk of the agents used for CHF are originate from other cardiovascular sectors. As such, the overall market involved in the treatment of CHF is a significant segment. The importance of the market will increase since the number of people affected by CHF is predicted to rise in the near future.


Chapter 1 will give the background to the disease and provide an up-to-date summary of the present understanding of the condition. Heart failure is a progressive disease that, once initiated, usually advances to a life-threatening state and in many cases, death. CHF is the only major cardiovascular disorder that is steadily rising in incidence and prevalence. Worldwide, 2 million new cases are diagnosed each year and heart failure is one of the leading causes of hospitalisation in people over 65 years of age.


The medical management of CHF is based on two main criteria. The first is short-term treatment to alleviate the symptoms of the disease and the second criteria is a long-term strategy to stop or slow down the progression of the disease. Chapter 2 will review the medical treatment options available, with a particular focus on the new treatment paradigm. Traditional drugs in CHF include diuretics, coronary vasodilators and cardiostimulants, which aid the functioning of the heart. However, in recent years the focus has moved onto the neurohormonal influences in CHF and in particular the role they play in the structural changes of the heart. Consequently, angiotensin converting enzyme (ACE) inhibitors and beta-blockers have come to the fore in the management of CHF. The importance of these drugs in the treatment of heart failure is directly related to new understanding of the role that the renin-angiotensin system and the sympathetic nervous system play in the progression of heart failure. However, the optimum therapeutic options are still not being used to their full potential and the ACE inhibitors and beta-blockers are still underprescribed for CHF.


Chapter 2 will also examine the emerging role of the angiotensin II antagonists in the management of CHF. Clinical trials with these agents have provided promising results and they appear to be comparable to the ACE inhibitors.


Chapter 3 will focus on the drugs in development for CHF. Incara's Bextra (bucindolol) was being evaluated in patients with moderate-to-severe CHF but the trial results have not been successful. However, Bristol-Myers Squibb's vasopeptidase, omapatrilat, is looking promising. The potential of endothelin antagonists to prevent cardiac remodelling is an exciting prospect but the development of these agents may have been set back by the troubles encountered by the leading product in development, Actelion's bosentan. Other novel approaches that have looked promising in early development are the cytokine inhibitors and aldosterone antagonists.


Scios' nesiritide (Natrecor), a recombinant form of brain atriuretic peptide, if successful, will be the first new agent approved for the treatment of acute heart failure in many years. However, Natrecor has failed to gain approval in the US after receiving an initial approval recommendation by the US Food and Drug Administration regulatory review panel.

© PJB Publications Ltd. 2000
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