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Stakeholder Insight: Atherosclerosis - HDL, ApoA-I, Carotid MRI and 64-slice CT offer opportunities for future treatmentPublished by: Datamonitor Published: Dec. 21, 2006 - 179 Pages Table of ContentsTABLE OF CONTENTS About the Cardiovascular pharmaceutical analysis team 2 CHAPTER 1 EXECUTIVE SUMMARY 4 Objective of the analysis 4 Datamonitor insight into the atherosclerosis market 4 CHAPTER 2 MARKET OVERVIEW 13 Market coverage for this report 13 Introduction 13 Pathogenesis of atherosclerosis 14 Atherogenic risk factors 15 Atherogenic protective factors 18 Histopathology of atherosclerotic lesions 18 Role of endothelium 19 Role of lipoproteins 21 Role of inflammation 22 C-reactive protein 22 Role of infection 24 Plaque growth and vascular remodeling 26 Positive remodeling 27 Negative remodeling 27 Stenosis severity and clinical events 27 CHAPTER 3 EPIDEMIOLOGY OF ATHEROSCLEROSIS 29 Objectives 29 Overview 29 Methods 30 Disease Definition 30 Measures of sub-clinical atherosclerosis 31 Carotid intima-media thickness (CIMT) 31 Coronary artery calcium score (CAC) 32 Ankle-brachial index (ABI) 32 Pulse wave velocity (PWV) 33 Atherosclerosis related epidemiologic studies 33 Risk Factors 33 Risk Factors and Cardiovascular Outcomes 36 Epidemiology Estimates 37 United States 38 Europe 38 European Statistics 39 United Kingdom 39 Japan 41 Review of literature on the prevalence of sub-clinical atherosclerosis. 41 Risk factors and outcomes associated with atherosclerosis 50 Risk Factors and co-morbidities 50 Hypertension 50 Dyslipidemia 52 Diabetes 56 Obesity 58 Outcomes of Atherosclerosis 60 CHAPTER 4 CURRENT CLINICAL PRACTICE 63 Diagnosis of atherosclerosis 63 Spectrum of presentation 63 Diagnostic procedures 65 “Gold standard” treatment 67 Medical care 67 Relief of symptoms 67 Prevention of future cardiac events 68 Statins 68 Treatment regimens 77 Treatment of vulnerable plaques 79 Surgical care 82 Percutaneous coronary interventions 82 Coronary artery bypass surgery 83 Other surgical procedures 83 Further inpatient care 84 Further outpatient care 85 Unmet needs in primary prevention 86 Unmet needs in secondary prevention 90 Views on plaque stabilization (with and without outcomes data) 93 Views on plaque regression (with and without outcomes data) 94 Will ASTEROID change clinical practice? 96 CHAPTER 5 PLASMA BIOMARKERS 100 How useful are plasma biomarkers? 100 C-reactive protein 100 Homocysteine 102 Emerging plasma biomarkers 103 Lipoprotein-associated phospholipase A2 103 Myeloperoxidase 105 Oxidized LDL 107 Lipoprotein (a) 108 Isoprostanes 109 Small, dense LDL 110 Other plasma markers 112 Drivers and barriers to greater use 113 CHAPTER 6 IMAGING STUDIES AND PROCEDURES 115 Introduction 115 Currently used imaging studies 118 Echocardiography 118 Nuclear imaging studies 118 Electron beam CT scanning 119 Currently used imaging procedures 120 Coronary angiography 120 Coronary blood flow determinations 120 Intravascular ultrasound 121 Emerging imaging techniques 124 Non-invasive imaging techniques 124 Magnetic resonance of coronary arteries 124 Multidetector row computed tomography angiography (MDCTA) 125 Multislice computed tomography (MSCT) 126 Positron emission tomography (PET) (detection of inflammation in vulnerable plaques) 126 Invasive imaging techniques 127 Intravascular MRI 127 Near-IR spectroscopy 128 Palpography 128 CHAPTER 7 COMPOUNDS IN DEVELOPMENT 131 ApoA-I mimetic ETC-216 (Pfizer/Esperion) 131 ApoA-I mimetic D-4F (Novartis/Bruin) 133 CETP inhibitors 134 Torcetrapib (Pfizer) 135 JTT-705 (Japan Tobacco and Roche) 136 CETP vaccine (Avant Immunotherapeutics) 137 AGI-1067 (AtheroGenics/AstraZeneca) 137 Nicotinic acid agonists 142 Gemfibrozil 142 PPARs 143 Gene therapy 143 Endothelial lipase 144 LXR agonists 144 MTP inhibitor 144 CHAPTER 8 FUTURE COMMERCIAL FOCUS 145 “Gold standard” diagnosis pathway in 5 years time 145 “Gold standard” treatment in 5 years time 146 Most promising advances/compounds in development 148 Where future funding should be focused 150 APPENDIX A 153 EPIDEMIOLOGY STUDIES 153 Multi-Ethnic Study of Atherosclerosis (MESA) (1999-2009) 153 Atherosclerosis Risk in Communities (ARIC) (1985-2006) 153 The Coronary Artery Disease Risk Development in Young Adults (CARDIA) (1984-2003): 154 Framingham Heart Study: (1948-2001) 155 Cardiovascular Health Study (CHS) (1988-2005) 155 Insulin Resistance Atherosclerosis Study (IRAS): Insulin, Insulin Resistance, Hyperglycemia and Cardiovascular Disease (1995-1999) 156 National Health and Nutrition Examination Survey (NHANES IV) (1997-2004) 156 Pathobiological Determinants of Atherosclerosis in Youth Study (PDAY): 157 The Rotterdam Study 157 Kuopio Ischemic Heart Disease Study 158 West of Scotland Coronary Prevention Study (WOSCOPS) 158 Bogalusa Heart Study (1972-2005) 159 Atherosclerosis risk in young adults (ARYA) study 159 BIBLIOGRAPHY 160 References 160 Epidemiology References 165 APPENDIX B 176 Contributing experts 176 About Datamonitor 177 About Datamonitor Healthcare 177 About the Cardovasular analysis team 178 Disclaimer 179 AbstractIntroductionAtherosclerosis generally begins in childhood and manifests clinically in mid-to-late adulthood. While the mortality from atherosclerotic conditions has declined significantly, in developed countries cardiovascular disease accounts for nearly 50% of all deaths, and within the next 15-20 years, is projected to surpass infectious diseases to become the leading cause of death worldwide. Scope Understand key opinion leaders' (KOL) views on topical issues in the atherosclerosis field Provide epidemiological data for the prevalence of atherosclerosis and its associated risk factors and outcomes Explore the pipeline and discuss mechanisms of action of developmental agents for the treatment of atherosclerosis Assess the value of emerging plasma biomarkers in the identification and treatment of atherosclerosis Highlights While screening for sub-clinical stages of atherosclerosis could potentially be beneficial in avoiding future cardiovascular events, a barrier to screening for primary prevention is the cost involved in the screening and the implication of identifying somebody at risk being the decision to begin treatment at an early stage. It would be possible to envision a screening system based on the standard risk factors, blood biomarkers, and non-invasive imaging methods. Such a screening system would identify asymptomatic individuals at high risk. However this would produce the dilemma on whether catheterization should be performed on individuals with no cardiac symptoms. For patients with atherosclerosis, diagnosis is usually based on coronary angiography. If significant stenosis is detected, treatment consists of PCI or CABG followed by medical management. Although it is widely acknowledged that the benefits of medical therapy are substantial, room for improvement remains, as exemplified by the PROVE-IT study. Reasons to Purchase Target physicians more effectively, through an understanding of treatment options and prescription choices Identify the current clinical practice in terms of diagnosis, medical and surgical care Recognize lucrative target populations, in terms of unmet need and patient potential, in order to successfully position developmental products Get Full Details About This Report >> |
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