Scrip's Complete Guide to Cardiovascular Diseases

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 coronary heart disease
1.2 Diagnostic assessment of atherosclerosis and CHD
1.2.1 Early diagnosis tests
1.2.1.1 Blood tests
1.2.1.2 Exercise electrocardiography
1.2.1.3 Stress echocardiography
1.2.1.4 Nuclear perfusion imaging
1.2.1.5 Coronary angiography
1.2.1.6 Emerging diagnostic tools
1.2.2 Diagnosis of a coronary event
1.3 Pathophysiology of CHD - atherosclerosis
1.3.1 Components of the atherosclerotic process
1.3.1.1 Response to injury hypothesis
1.3.1.2 Endothelial dysfunction
1.3.1.3 Cell migration and proliferation
1.3.1.4 Lipoproteins
1.4 Incidence and prevalence of CHD
1.4.1 Special populations
1.4.1.1 Elderly
1.4.1.2 Sex
1.4.1.3 Racial and ethnic groups
1.4.1.4 Socio-economic background
1.5 The economic cost of CHD
1.6 Risk factors for CHD
1.6.1 Hypertension
1.6.2 Obesity
1.6.3 Lipid levels and diet
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 CHD
1.7.1 Angina pectoris
1.7.2 Acute coronary syndromes
1.7.2.1 Unstable angina
1.7.2.2 Myocardial infarction
1.7.2.3 Sudden cardiac death
1.8 Management of CHD
1.8.1 Non-pharmacological management
1.8.1.1 Lifestyle adjustments in primary and secondary prevention
1.8.1.2 Interventional procedures
1.8.2 Pharmacological management
1.8.2.1 Primary and secondary prevention
1.8.2.2 Treatment of ischaemic events
1.9 Conclusion

CHAPTER 2 CORONARY HEART DISEASE DRUGS ON THE MARKET
2.1 Introduction
2.1.1 Treatment guidelines
2.2 Primary prevention
2.2.1 Aspirin
2.2.2 Traditional lipid-lowering drugs
2.2.2.1 Bile acid sequestrants
2.2.2.2 Fibrates
2.2.2.3 Nicotinic acid
2.2.3 HMG-CoA reductase inhibitors
2.2.3.1 Atorvastatin
2.2.3.2 Cerivastatin
2.2.3.3 Fluvastatin
2.2.3.4 Lovastatin
2.2.3.5 Pravastatin
2.2.3.6 Simvastatin
2.3 Treatment of CHD
2.4 Treatment of angina
2.4.1 Nitrates and nitroglycerin
2.4.1.1 Nitroglycerin
2.4.1.2 Isosorbide mononitrate
2.4.1.3 Isosorbide dinitrate
2.4.2 Beta-blockers
2.4.3 Calcium channel blockers
2.4.3.1 Dihydropyridines
2.4.3.2 Benzothiazepines
2.4.3.3 Phenylalkylamines
2.4.4 Potassium channel openers
2.4.4.1 Nicorandil
2.5 Treatment of acute coronary syndromes
2.5.1 Thrombolytics
2.5.1.1 First-generation thrombolytics
2.5.1.2 Second-generation thrombolytics
2.5.2 Antiplatelet agents
2.5.2.1 Aspirin
2.5.2.2 Clopidogrel
2.5.2.3 Ticlopidine
2.5.2.4 Glycoprotein IIb/IIIa receptor antagonists
2.5.3 Antithrombotic agents
2.5.3.1 Heparin
2.5.3.2 Low molecular weight heparins
2.5.3.3 Direct thrombin inhibitors
2.6 Secondary prevention
2.7 Conclusion

CHAPTER 3 CORONARY HEART DISEASE DRUGS IN DEVELOPMENT
3.1 Introduction
3.2 Thrombolytics in development
3.2.1 Lanoteplase
3.2.2 TNK-tPA
3.2.3 Saruplase
3.2.4 Other thrombolytics in development
3.3 Antiplatelet drugs in development
3.3.1 Intravenous GPIIb/IIIa inhibitors in development
3.3.1.1 Fradafiban
3.3.1.2 Klerval
3.3.1.3 Lamifiban
3.3.2 Oral GPIIb/IIIa inhibitors in development
3.3.2.1 CT-50352
3.3.2.2 Lefradafiban
3.3.2.3 Lotrafiban
3.3.2.4 Orbofiban
3.3.2.5 Sibrafiban
3.3.2.6 Xemilofiban
3.4 Antithrombotic agents in development
3.4.1 Direct acting thrombin inhibitors
3.4.1.1 Bivalirudin
3.4.1.2 Inogatran
3.4.1.3 Efegatran
3.4.1.4 LU-57291
3.4.1.5 TRI-50B
3.4.2 Low molecular weight heparins
3.4.2.1 OP-2000
3.5 Cholesterol-lowering drugs in development
3.5.1 HMG-CoA reductase inhibitors
3.5.1.1 HBS-107
3.5.1.2 NK-104
3.5.1.3 S-4522
3.5.2 Non-statin lipid-lowering drugs
3.5.2.1 Colesevelam hydrochloride
3.5.2.2 Colestilan
3.5.2.3 Lifibrol
3.6 New directions and novel drugs in CHD treatment
3.7 Antianginal agents with new mechanisms of action
3.7.1 JTV-506
3.7.2 KRN-2391
3.7.3 Fasudil
3.7.4 Mivazerol
3.7.5 Molsidomine
3.7.6 Ranolazine
3.7.7 Sinitrodil
3.8 Adenosine
3.8.1 GP-531
3.8.2 N-0861
3.8.3 Pallacor
3.8.4 RPR-100579
3.9 Sodium-hydrogen exchange inhibitors
3.9.1 Cariporide
3.9.2 Eniporide mesilate
3.10 Immunotherapy
3.10.1 5G1.1-SC
3.10.2 CETi-1 vaccine
3.10.3 Complement inhibitors
3.10.4 TP10
3.11 Gene therapy
3.11.1 Vascular endothelial growth factor
3.11.1.1 Vascular endothelial growth factor products in preclinical development
3.11.1.2 Vascular endothelial growth factor products in clinical trials
3.11.2 Fibroblast growth factors
3.11.3 Angiogenesis inhibitors
3.12 Other new treatments for CHD under investigation
3.13 Conclusion

REFERENCES

LIST OF TABLES
Table M.1 Average exchange rates against the US$, 1996-1998
Table 1.1 Diagnostic groupings of acute chest pain based on ECG characteristics
Table 1.2 Enzyme markers associated with MI
Table 1.3 Lipid levels associated with increased risk of CHD
Table 1.4 The Canadian Cardiovascular Society Functional Classification for Angina Pectoris
Table 1.5 Drugs for the primary prevention of atherosclerosis and CHD
Table 1.6 Drugs for secondary prevention of acute coronary events
Table 1.7 Drugs for the treatment of angina
Table 1.8 Drugs for the treatment of acute coronary events
Table 2.1 Marketed nitroglycerin preparations
Table 2.2 Isosorbide mononitrate preparations available on the market
Table 2.3 Isosorbide dinitrate preparations available on the market
Table 2.4 Cardioselective beta-blockers indicated for angina
Table 2.5 Non-selective beta-blockers indicated for angina
Table 2.6 Dihydropyridine calcium channel blockers indicated for angina
Table 2.7 Benzothiazepines and phenylalkylamines indicated for angina
Table 2.8 Marketed tPA agents
Table 2.9 Mortality results from trials comparing alteplase with streptokinase
Table 2.10 Results of clinical trials with ReoPro and a thrombolytic
Table 2.11 Drugs for secondary prevention of acute coronary events
Table 2.12 Trials involving ACE inhibitors in secondary prevention of CHD
Table 2.13 ACE inhibitors indicated for CHD-related events
Table 3.1 Thrombolytics in development
Table 3.2 Intravenous GPIIb/IIIa inhibitors in clinical development
Table 3.3 Oral GPIIb/IIIa inhibitors in clinical development
Table 3.4 Antithrombotic inhibitors in development
Table 3.5 Statins in development
Table 3.6 Lipid-lowering drugs in development
Table 3.7 Antianginal drugs in development
Table 3.8 Adenosine agents in development for CHD-related events
Table 3.9 Immunotherapies in development for the treatment of atherosclerosis/CHD
Table 3.10 Companies developing vascular endothelial growth factor gene therapy for CHD
Table 3.11 Companies developing fibroblast growth factor gene therapy for CHD

LIST OF FIGURES
Figure 1.1 The different stages of atherosclerosis
Figure 1.2 Prevalence of CHD by age and sex in the US, 1988-1994
Figure 1.3 CHD mortality in males aged 20-64 years by socio-economic background in the UK

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

Volume 1: CVD Market Overview (BS1031)
Volume 2: Hypertension (BS1032)
Volume 4: Arrhythmia (BS1034)
Volume 5: Congestive Heart Failure (BS1035)
Volume 6: Stroke (BS1036)

EXECUTIVE SUMMARY
Innovative products, new product launches and one of the fastest growing segments in the industry have all contributed to the success of the market for atherosclerosis/coronary heart disease (CHD). The market for cholesterol and triglyceride-lowering agents is currently valued at $12.8 billion and treatments for acute ischaemic attacks is valued at over $3 billion per year.

Chapter 1 discusses the latest progress in the understanding of CHD. The disease itself is the highest single cause of mortality in the world. The consequences of CHD are felt throughout the spectrum of cardiovascular disease and it is associated with the development of congestive heart failure, arrhythmia and stroke.

Chapter 2 reviews the drugs marketed for the treatment of CHD, from primary and secondary prevention to acute coronary syndromes. The phenomenal growth of the statins reflects the real need to effectively manage CHD. These agents have the potential to stop further heart attacks and even prevent the occurrence of a first heart attack in high-risk patients. Thus, the statins have been both a medical and commercial success. In the near future, statins are predicted to be the world's leading drugs in terms of sales, surpassing the high-selling antiulcer agents.

In the treatment of acute ischaemic attacks - such as unstable angina, non-Q-wave myocardial infarction (MI) and acute MI - novel therapeutic agents have been introduced, which promise to save more lives. Traditionally, the emergency treatment of unstable angina and non-Q-wave MI involved the use of antithrombotics (aspirin and heparin) whilst the treatment of acute MI favoured the use of thrombolytics (streptokinase) for MI.

Low molecular weight heparin, direct thrombin inhibitors and glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonists show promise over the standard treatment options of aspirin and heparin. A number of clinical trials have shown that these agents have a comparable or better efficacy to aspirin or heparin but the cost effectiveness of the latter agents will mean that the new agents will have to demonstrate significantly improved benefits agents to succeed.

Second-generation thrombolytics, such as the tissue plasminogen activators alteplase and reteplase, offer significant advantages over the older thrombolytic, streptokinase. Alteplase and reteplase do not have the immune response associated with streptokinase. In addition, the second-generation thrombolytics increase the chances of a positive outcome.

R&D in CHD-related therapy is constantly evolving as investigators attempt to improve on the current therapeutic modalities. Chapter 3 provides an overview of the current status of research in this area with commentary on the drugs likely to succeed or fail in this therapeutic category. Research has started to focus on the combined use of a thrombolytic with an antiplatelet drug and preliminary trials using such combinations indicate this may be the way forward in the acute treatment of heart attacks. The future for oral GPIIb/IIIa antagonists is bleak and poor clinical trial results have led to a number of companies discontinuing development of these oral agents. Antithrombotic drugs in development have also faced problems mainly because they have not shown a sufficient increase in benefit over heparin. Although new therapeutic approaches using immunotherapy and gene therapy are still a long way from market, these agents have shown some promising results in preclinical and early clinical trials and hold exciting possibilities.