Innovations in Cardiovascular Disease Management: Latest surgical procedures, drugs and medical devices

Executive Summary 10
The Management of Cardiovascular Disease 10
Cardiovascular and Interventional Procedures 11
Emerging Coronary Stents and Stent Systems 12
Innovations in Minimally Invasive Cardiac Surgery 13
Cardiovascular Drugs in Early Stage Development 14
New and Emerging Cardiovascular Drugs 14

Chapter 1 The Management of Cardiovascular Disease 18
Summary 18
Introduction 19
The Global Burden of Cardiovascular Disease 19
CVD remains the leading cause of death in the United States 19
CVD Rates in Central and Eastern Europe 21
Noncommunicable Diseases in the Developing World 21
Background to the Major Cardiovascular Conditions 23
Coronary Artery Disease (CAD) 23
Atherosclerosis 23
Angina Pectoris 25
Acute Myocardial Infarction (MI) 27
Heart Valve Disorders 29
Aortic heart valve 29
Mitral Valve Disease 30
Pulmonary Valve Disease 32
Tricuspid Valve Disease 32
High Blood Pressure: Hypertension 32
Heart Rhythm Disorders (Heart Arrhythmia) 33
Peripheral Vascular Disease 35
Peripheral Artery Disease (PAD) 35
Peripheral Venous Disorders (PVD) 37
Stroke or Cerebrovascular Accidents (CVA) 38
Ischaemic Stroke 38
Haemorrhagic stroke 38

Chapter 2 Latest Developments in Cardiovascular and PCI Procedures 42
Summary 42
Introduction to Percutaneous Coronary Interventions 43
Indications for PCI 44
PCI Procedural Volumes 44
PCI Used Primarily to Treat Unstable Angina and acute ST-elevation MI 45
Inter-country Variance in PCI Procedural Rates 46
China and India: Huge growth potential and market development 47
Latest Developments in PCI Procedures 49
Embolic Protection Devices 49
Current Products 50
Development Stage Products and Current Status 55
Future Technologies and Trends 58
Coronary Atherectomy 59
Rotational Coronary Atherectomy (Rotoblation) 59
Directional Coronary Atherectomy (DCA) 59
Orbital Atherectomy 60
Ablative laser-assisted angioplasty 60

Chapter 3 Emerging Coronary Stents and Stent Systems 64
Summary 64
Emerging Coronary Stents and Stent Systems 65
Key Events 65
Introduction of Drug-Eluting Stents (DES) 67
Development of Drug-Eluting Stents 70
Sirolimus (Rapamycin) 70
Paclitaxel 71
Tacrolimus 72
Everolimus (RAD-001) 73
Zotarolimus (also called ABT-578) 73
DES – Recent News, Product Developments and Clinical Trial Updates 74
Market Developments and Forecasts for Drug-Eluting Stents 77
Emergence of Bioabsorbable Stents 82
Biomaterials and Bioabsorbable Polymers 83
Further Coronary Stent Developments and Technological Trends 85
Novel Coating Technologies 85
Gene Therapy technologies and its Potential Use to Prevent Restenosis 86
Coronary Stents and Endothelial Progenitor Cells (EPCs) 87
Nanotechnologies and Drug-Eluting Coronary Stents 88
Development of Novel Estradiol Containing Drug-Eluting Stents 88
Stem-Cell Derived Endovascular Cells 89

Chapter 4 Innovations in Minimally Invasive Cardiac Surgery (MICS) 92
Summary 92
Introduction 93
Minimally Invasive Direct Coronary Artery Bypass (MID-CAB) 93
Indications for MIDCAB 94
Off-Pump Coronary Artery Bypass (OP-CAB) 94
Indications for OP-CAB 94
Minimally Invasive Port Access 95
Indications for Minimally Invasive Port Access 96
Robotic Assisted Coronary Artery Bypass (RA-CAB) 96
Current and Emerging Technologies 98
Robotics in Minimally Invasive Cardiac Surgery 98
Robotic Systems 98
Computer Aided Cardiac Surgery 100
Virtual Reality in Cardiac Surgery 100
Laser Heart Surgery or transmyocardial Laser revascularization (TMLR) 101
The CO2 Heart Laser System 101
The holmium:YAG (yttrium aluminium garnet) laser 102
The excimer laser 102

Chapter 5 Cardiovascular Drugs in Early Stage Development 106
Summary 106
Introduction 107
Early Developments in Key Cardiovascular Disease Classes 107
Angina 107
Arrhythmiasis 110
Atherosclerosis 112
Atrial Fibrillation 115
Congestive Heart Failure 116
Hypercholesterolemia 118
Hypertension 120
Myocardial Infarction 122
Thrombosis 124

Chapter 6 New and Emerging Cardiovascular Drugs 128
Summary 128
Introduction 129
Anti-Hypertensives 129
Tekturna (Aliskiren) 130
Development of a New Class of Renin Inhibitors 132
Exforge (valsartan plus amlodipine) 133
CHF-1521 134
Cleviprex(TM) (Clevidipine) 135
Antihypertensives: Current Pipeline and Late Stage Development 136
Cardoxal (MC-4232) (MC-1 cardioprotectant plus lisinopril) 138
Darusentan 139
Ambrisentan 139
Nebivolol 140
Zanipress® / Zanitek® 140
Thelin™ (Sitaxsentan) 141
TBC3711 142
Anti-Dyslipidemics 143
Pfizer discontinues torcetrapib development 144
R1658 145
Simcor (Niaspan® (extended-release niacin) and simvastatin (generic
Zocor®)) 145
CRESTOR® (rosuvastatin) and CRESTOR/ABT-335 combination 147
Synordia 149
Lapaquistat (TAK-475) 150
SLx-4090 151
AEGR-733 152
Compound Number 256073 and 501516 153
LBM642 153
Dyslipidaemia: Current Pipeline and Late Stage Development 154
Anti-Thrombotics 156
Rivaroxaban (BAY59-7939) 156
Rendix (dabigatran etexilate, BIBR-1048) 157
Idraparinux 157
Apixaban 158
SSR-126517 158
Exanta/ximelagatran 159
Anti-Thrombotics: Current Pipeline and Late Stage Development 160
Anti-Arrhythmics 161
Stedicor (Azimilide) 163
Multaq (Dronedarone) 164
Vernakalalant (RSD 1235) 165
Tecadenoson CVT510 167
Pulzium IV (Tedisamil) 167
Anti-Arrhythmics: Current Pipeline and Late Stage Development 168

Chapter 7 Appendix 170
Methodology Statement 170
Primary Data and Information Gathering 170
Secondary Data and Information Gathering 170
Market Share Analysis and Market Forecast Predictions 171
Glossary 173
Index 182

List of Figures
Figure 1.1: Breakdown of Deaths from Cardiovascular Diseases, USA 2002 20
Figure 1.2: Leading causes of death in developing countries, 2002 23
Figure 2.3: Use of Percutaneous Coronary Intervention in Europe, 2005 46
Figure 3.4: Estimated number of Stent Procedures (BMS & DES) % Total Number of PTCA
Procedures 69
Figure 3.5: Actual and projected revenues from Coronary Stents, Worldwide sales- 2006 81
Figure 3.6: Market Share Analysis, DES v BMS World, 2006 82

List of Tables
Table 1.1: Age- and gender-specific incidence of recognised MI 28
Table 1.2: Age- and gender-specific incidence of unrecognised MI 28
Table 2.3: Estimated volume of cardiovascular procedures by region (US 2002) 45
Table 2.4: PCI procedure rates in Selected Countries, 2005 49
Table 5.5: Selected Early Stage Anti Anginal Drug Developments 108
Table 5.6: Selected Early Stage Anti Arrhythmiasis Drug Developments 110
Table 5.7: Selected Early Stage Atherosclerosis Drug Developments 112
Table 5.8: Selected Early Stage Atrial Fibrillation Drug Developments 115
Table 5.9: Selected Early Stage Congestive Heart Failure Drug Developments 116
Table 5.10: Selected Early Stage Hypercholesterolemia Drug Developments 118
Table 5.11: Selected Early Stage Hypertension Drug Developments 120
Table 5.12: Selected Early Stage Myocardial Infarction Drug Developments 122
Table 5.13: Selected Early Stage Thrombosis Drug Developments 125
Table 6.14: Characteristics of Major Classes of Lipoproteins 144
Table 6.15: AstraZeneca’s Current Anti-Dyslipidaemia Pipeline 149
Table 6.16: Classification of Anti-Arrhythmics 162