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 hypertension
1.1.1 Classification of hypertension
1.1.1.1 WHO definitions
1.1.1.2 US JNC VI definition
1.1.1.3 Subclassifications of hypertension
1.2 Diagnosis of hypertension
1.3 Pathophysiology of hypertension
1.3.1 Neural control of blood pressure
1.3.2 Hormonal control of blood pressure
1.3.3 Renal control of blood pressure
1.3.4 Nitric oxide
1.3.5 Endothelin
1.3.6 Genetic aspects of hypertension
1.4 Incidence and prevalence of hypertension
1.4.1 Special populations
1.4.1.1 Elderly
1.4.1.2 Racial and ethnic groups
1.4.1.3 Sex
1.4.1.4 Children
1.4.1.5 Socio-economic background
1.5 The economic cost of hypertension
1.6 Risk factors for hypertension
1.6.1 Obesity
1.6.2 Alcohol
1.6.3 Dietary sodium and calcium
1.6.4 Sedentary lifestyle
1.6.5 Diabetes and insulin resistance
1.6.6 Smoking
1.6.7 Other factors
1.7 Complications associated with hypertension
1.7.1 Left ventricular hypertrophy
1.7.2 Congestive heart failure
1.7.3 Atherosclerosis and coronary heart disease
1.7.4 Stroke
1.7.5 Renal disease
1.7.6 Retinopathy
1.7.7 Aortic and peripheral artery disease
1.8 The management of hypertension
1.8.1 Non-pharmacological management
1.8.1.1 The DASH diet
1.8.2 Pharmacological management
1.9 Conclusion


CHAPTER 2 ANTIHYPERTENSIVE DRUGS ON THE MARKET
2.1 Introduction
2.1.1 Treatment guidelines
2.2 Diuretics
2.2.1 Thiazide diuretics
2.2.1.1 Bendrofluazide
2.2.1.2 Hydrochlorothiazide
2.2.2 Thiazide-like diuretics
2.2.2.1 Chlorthalidone
2.2.2.2 Indapamide
2.2.3 Loop diuretics
2.2.3.1 Frusemide
2.2.3.2 Piretanide
2.2.4 Potassium-sparing diuretics
2.3 Beta-blockers
2.3.1 Acebutolol
2.3.2 Atenolol
2.3.3 Bisoprolol
2.3.4 Carvedilol
2.3.5 Labetalol
2.3.6 Metoprolol
2.3.7 Nadolol
2.3.8 Nebivolol
2.3.9 Propranolol
2.3.10 Timolol
2.4 ACE inhibitors
2.4.1 Benazepril
2.4.2 Captopril
2.4.3 Delapril
2.4.4 Enalapril
2.4.5 Fosinopril
2.4.6 Lisinopril
2.4.7 Moexipril
2.4.8 Perindopril
2.4.9 Quinapril
2.4.10 Ramipril
2.4.11 Trandolapril
2.5 Calcium channel blockers
2.5.1 Amlodipine
2.5.2 Diltiazem
2.5.3 Felodipine
2.5.4 Isradipine
2.5.5 Lacidipine
2.5.6 Lercanidipine
2.5.7 Mibefradil
2.5.8 Nicardipine
2.5.9 Nifedipine
2.5.10 Nisoldipine
2.5.11 Nitrendipine
2.5.12 Verapamil
2.6 Angiotensin II antagonists
2.6.1 Candesartan
2.6.2 Eprosartan
2.6.3 Irbesartan
2.6.4 Losartan
2.6.5 Tasosartan
2.6.6 Telmisartan
2.6.7 Valsartan
2.7 Alpha-blockers
2.7.1 Bunazosin
2.7.2 Doxazosin
2.7.3 Prazosin
2.7.4 Terazosin
2.8 Centrally-acting agents
2.8.1 Clonidine
2.8.2 Methyldopa
2.8.3 Moxonidine
2.8.4 Reserpine
2.8.5 Rilmenidine
2.9 Primary vasodilators
2.10 Other antihypertensives
2.10.1 Dopamine agonists
2.10.1.1 Fenoldopam
2.10.2 Serotonergic antagonists
2.10.2.1 Ketanserin
2.10.2.2 Urapidil
2.11 Conclusion


CHAPTER 3 HYPERTENSIVE DRUGS IN DEVELOPMENT
3.1 Introduction
3.2 Endothelin antagonists
3.2.1 Bosentan
3.2.2 J-104132
3.2.3 YM-598
3.3 Neutral endopeptidase inhibitors
3.3.1 Ecadotril
3.3.2 Candoxatril
3.3.3 Omapatrilat
3.3.4 Mixanpril
3.3.5 Fasidotril
3.3.6 Sampatrilat
3.3.7 BMS-189921
3.4 Dopamine agonists
3.5 Potassium channel inhibitors
3.6 Renin inhibitors
3.7 Adenosine agents
3.7.1 N-0861
3.8 Phosphodiesterase inhibitors
3.9 New research areas
3.9.1 Vaccines for hypertension
3.9.2 Antisense gene therapy
3.10 Developmental agents in established drug classes
3.10.1 ACE inhibitors
3.10.1.1 Zofenopril
3.10.2 Calcium channel blockers
3.10.3 Angiotensin II antagonists
3.10.4 Combination products
3.11 Conclusion


REFERENCES

LIST OF TABLES
Table M.1 Average exchange rates against the US$, 1996-1998
Table 1.1 Causes of secondary hypertension
Table 1.2 WHO-ISH classification of hypertension by blood pressure level
Table 1.3 US JNC VI classification of hypertension
Table 1.4 Trends in the control of hypertension in the US, 1976-1994
Table 1.5 Risk stratification and antihypertensive treatment
Table 1.6 Drugs for the treatment of hypertension
Table 2.1 WHO guidelines for selecting drug treatment for hypertension
Table 2.2 Comparison of the drugs used in the treatment of hypertension
Table 2.3 Characteristics of the main beta-blockers
Table 2.4 Characteristics of calcium channel blockers
Table 2.5 Pharmacokinetics of the angiotensin II antagonists
Table 3.1 Endothelin antagonists in development
Table 3.2 Neutral endopeptidase inhibitors in development
Table 3.3 Dopamine agonists in development
Table 3.4 Potassium channel inhibitors in development
Table 3.5 Renin inhibitors in development
Table 3.6 Adenosine agents in development
Table 3.7 Phosphodiesterase inhibitors in development
Table 3.8 Calcium channel blockers in development
Table 3.9 Angiotensin II antagonists in development
Table 3.10 Combination products in development

LIST OF FIGURES
Figure 1.1 Prevalence of hypertension with increasing age (US)
Figure 1.2 Estimated prevalence trends for hypertension by sex and race in the US, 1988-1994


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

 

EXECUTIVE SUMMARY
Antihypertensive agents are the largest single therapeutic class within the cardiovascular disease category. Agents from this therapeutic group are consistently strong performers. The important status of anithypertensive drugs is reflected by the $22 billion value of the market. Furthermore, the market is predicted to experience a 24% growth by the year 2002.


Chapter 1 provides the background to hypertension, which affects about 20% of the adult population. This chapter also highlights the groups most at risk from high blood pressure.


Antihypertensive agents are one of the most prescribed drugs in the developed world and they are consistently ranked as top-selling products. However, the problems of patent expiry and generic competition threaten to affect this lucrative market. Chapter 2 analyses the strengths and weaknesses of the marketed agents. Traditional first-line agents such as the beta-blockers have relied on line extensions and additional indications to maintain their market share. Even these strategies have not been completely successful and sales of branded products have slowly declined. Calcium channel antagonists and angiotensin converting enzyme (ACE) inhibitors are the strongest performers in the antihypertensive category. These two classes of drugs have a combined market value of $15.2 billion. Nevertheless, the imminent patent expiration of the two leading ACE inhibitors, AstraZeneca's Zestril (lisinopril) and Merck & Co's Vasotec (enalapril) may adversely affect the market.


The leading calcium channel antagonists are less affected by patent issues and have shown impressive growth over recent years. Although calcium channel antagonists are not recommended as first-line drugs, they have increased in popularity. The newer dihydropyridine calcium channel blockers in particular have become widely used. This has been partly due to an increased marketing emphasis and the positive results from clinical trials demonstrating the beneficial effects of the agents. The recently published findings from the HOT study indicated that blood pressure reduction with the dihydropyridine, felodipine, significantly reduced cardiovascular risks (Hansson et al., 1998). The angiotensin II antagonists are relative newcomers to the antihypertensive field but have quickly gained market acceptance. The angiotensin II antagonists offer improvements in safety profile and equivalent efficacy of the other antihypertensive classes and their success is illustrated by Merck & Co's Cozaar (losartan), the first agent from this class to break the $1 billion sales barrier.


To improve their chances of succeeding in the extremely competitive antihypertensive market, new innovations will have to improve on the safety profile and efficacy of the established agents. Chapter 3 discusses the agents in development for hypertension, highlighting agents with novel mechanism of action and in late-stage development. The dual neutral endopeptidase/ACE inhibitors look to be one of the most promising compounds. These agents appear to have a good safety profile and have demonstrated favourable efficacy in trials compared with ACE inhibitors alone.

© PJB Publications Ltd. 2000
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