Acute Coronary Syndromes Fresh look at ACS in Europe, what is the real picture?

CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into the ACS market 4
Contributing experts 5
CHAPTER 2 ACS DEFINITIONS AND PATHOPHYSIOLOGY 7
Acute coronary syndromes 7
Definitions 7
Pathophysiology 8
Coronary artery disease and atherosclerosis 8
Vulnerable plaque 9
Histopathology of atherosclerotic lesions 10
Remodeling and role of coronary artery inflammation 12
Thrombosis 13
Atherosclerotic calcification 14
Ischemia 14
Unstable angina (UA) 15
Variant angina 17
Non-ST segment elevated myocardial infarction (NSTEMI) 17
Non-ST segment elevated myocardial infarction (NSTEMI) and ST segment elevated myocardial infarction (STEMI) 18
New definition of myocardial infarction 18
CHAPTER 3 EPIDEMIOLOGY 19
ACS epidemiology specifics and limitations 19
Ageing population 21
Male to female ratio and age 22
Risk factors 23
Smoking 24
Obesity and overweight prevalence 24
Diabetes 30
Hypertension 32
Dyslipidemia 34
Prevalence and incidence of ACS in the 5EU 36
Incidence of STEMI 36
Incidence of UA and NSTEMI 36
CHAPTER 4 DIAGNOSIS AND INVESTIGATION IN ACS 38
Symptoms 38
Initial and final diagnosis 38
Physical examination and chest pain differential 40
Clinical tests in primary investigation 41
ECG and ECG Stress testing 41
Cardiac biomarkers 42
Cardiac troponins 42
Creatine Kinase (CK) 43
Myoglobin 44
C-reactive protein (CRP) 44
Neurohormonal activation markers 44
Novel biomarkers 45
Multimarker approach 45
Risk stratification 46
Role of imaging tests in ACS 47
Invasive imaging testing 47
Coronary angiography 48
Intravascular ultrasound (IVUS) 49
Intravascular MRI (IVMRI) 50
Non-invasive imaging testing 51
Echocardiography and stress echo 51
Chest X-ray 54
Nuclear perfusion tests 54
Role of MRI and CT in coronary heart disease diagnosis 55
Limitations of early imaging in the emergency department 57
CHAPTER 5 PHARMACOLOGICAL STRATEGIES 58
Drug classes in ACS 58
Anti-ischemic agents 58
Nitrates 58
Betablockers 59
Calcium channel blockers 60
ACE inhibitors and angiotensin II receptor blockers 61
Antithrombotics 62
Anticoagulants 62
Heparins 62
Antiplatelet agents 65
COX-1 inhibitors (aspirin) 65
ADP receptor antagonists 66
GPIIb/IIIa receptor inhibitors 68
Thrombolytics 70
Fibrinolysis 70
Pharmacological reperfusion 70
Statins 72
CHAPTER 6 REVASCULARIZATION STRATEGIES 73
Coronary thrombolysis 73
Pre-hospital thrombolysis 73
In-hospital thrombolysis 74
Contraindications to fibrinolytic therapy 75
Interventions versus thrombolysis 76
Clinical trial evidence: C-PORT and a meta-analysis 76
Evidence from registries 77
Angioplasty 78
Stenting 80
In-stent restenosis: the man-made condition 81
Drug-eluting stents 81
ESC guidelines on PCI strategy in NSTE-ACS and STEMI 82
Coronary artery bypass graft (CABG) 84
CHAPTER 7 HOSPITAL INFRASTRUCTURE AND PATIENT FLOW 85
Overview 85
General practitioners and outpatient facilities 85
Role of ambulance services 86
Emergency department (ED) 87
Coronary care and intensive care unit 87
Cardiac catheterization laboratory (Cathlab) 88
CHAPTER 8 REVIEW OF CURRENT GUIDELINES 89
ESC guidelines 89
Recommendations by the ESC 89
Guidelines for STEMI patients 89
CHAPTER 9 KEY FIGURES AND STATISTICAL ANALYSIS 93
Methodology 93
Patient demographics 94
Main diagnosis 94
ACS age and sex distributions 96
Co-morbidities and risk factors 103
Diabetes 103
Dyslipidemia 104
Hypertension 105
Obesity 106
Smoking 107
ACS hospital logistics 109
Mode of admission 109
Mode of admission for patients with ST-segment elevation 111
Type of hospital for ACS patient admission. 112
The importance of cathlabs 113
Point of entry to hospital 114
First stage 114
Second stage 116
Length of stay in hospital 118
Hospital transfers 120
Diagnostic procedures 122
Cardiac biomarkers 122
Non-invasive imaging test 124
Reperfusion therapy 129
Thrombolytic therapy 129
Coronary interventions 133
Pharmacological therapy 137
Anticoagulants 137
Unfractionated heparins 137
Low molecular weight heparins 138
Antiplatelet agents 140
COX-1 inhibitors 140
ADP receptor antagonists 141
GPIIb/IIIa receptor inhibitors 142
Anti-ischemic agents 144
Nitrates 144
Betablockers 146
ACE inhibitors 148
Summary 149
APPENDIX 152
References 152
General sources 152
Obesity Epidemiology sources 154
France 154
Germany 154
Italy 154
Spain 154
UK 155
About Datamonitor 155
About Datamonitor Healthcare 155
About the Cardiovascular Disease analysis team 156
Disclaimer 157
List of Tables
Table 1: Prevalence of obesity in the seven major markets (000s), 2006-2015 26
Table 2: Prevalence of obesity / overweight in the seven major markets (000s), 2006-2015 27
Table 3: Estimated absolute prevalence of diabetes in the seven major markets (millions), 2006 31
Table 4: Prevalence of hypertension in the seven major markets (000s), 2003 34
Table 5: Estimated prevalent persons with dyslipidemia across the seven major markets, 2005 35
Table 6: Incidence of ST-segment elevation myocardial infarction (000s) 36
Table 7: Incidence of unstable angina and non-ST segment elevation myocardial infarction (000s) 37
Table 8: Types of chest pain 40
Table 9: Risk stratification summary for ACS, 2006 47
Table 10: Number of PCI procedures performed in the 5EU, 2005 80
Table 11: CABG procedures performed in the 5EU, 2005 84
Table 12: ESC guidelines for the management of STEMI, 2002 90
List of Figures
Figure 1: Development and progression of atherosclerosis 8
Figure 2: Pathogenesis of a plaque leading to rupture 10
Figure 3: ACS pathophysiology cycle 13
Figure 4: The 10 leading causes of death in high-income countries (%),2005 projections 19
Figure 5: Deaths attributed to specific cardiovascular diseases, 2006 20
Figure 6: Major causes of death in the 5EU, 2006 21
Figure 7: Distribution of the population in Europe by age, 2004 22
Figure 8: Distribution of the population in Europe by age, 2050 23
Figure 9: Basic diagnostic flow in ACS 39
Figure 10: Antiplatelet therapy in ACS 69
Figure 11: Ancrod acts indirectly on the thrombolytic pathways 71
Figure 12: Contraindications to fibrinolytic therapy 76
Figure 13: PCI procedures carried out by indication in the 5EU, 2005 79
Figure 14: Management of ACS without ST-elevation (NSTE-ACS) 83
Figure 15: Management of ACS in STEMI 83
Figure 16: Typical patient flow in case of acute chest pain 86
Figure 17: Delays in patients with acute chest pain 88
Figure 18: Proportion of patients presented with and without ST-segment elevation on initial ECG, 5EU, 2007 94
Figure 19: Ratio of main ACS diagnoses in 5EU 95
Figure 20: Overall ACS age distribution in the ACV analyzer sample 96
Figure 21: ACS age distribution split by country and sex 97
Figure 22: Changes in main diagnosis ratio in age distribution 99
Figure 23: Changes in main diagnosis ratio by age and sex, MALE 100
Figure 24: Changes in main diagnosis ratio by age and sex, FEMALE 100
Figure 25: Age-related variations in male:female ratio of ACS patients in the 5EU 101
Figure 26: Diabetes distribution among ACS patients in the 5EU 103
Figure 27: Dyslipidemia distribution among ACS patients in the 5EU 104
Figure 28: Hypertension distribution among ACS patients in the 5EU 105
Figure 29: BMI distribution among ACS patients in the 5EU 106
Figure 30: Percentage of patients who smoke in the ACS analyzer sample per country 107
Figure 31: Hospital admission mode for ACS patients 109
Figure 32: Mode of hospital admission for patients with ST-segment elevation 111
Figure 33: Patients admitted via ambulance to hospitals with or without cathlabs - all patients versus those with ST-segment elevation 112
Figure 34: Proportion of ACS patients admitted to hospitals with or without cathlab by all modes of admission - all patients versus those with ST-segment elevation 113
Figure 35: First stop in hospital after admission - all patients versus those with ST-segment elevation 114
Figure 36: Second stop in hospital after admission - all patients versus those with ST-segment elevation 117
Figure 37: Diagnostic challenge: Second stop in hospital after admission for patients without ST-segment elevation and with negative troponin 118
Figure 38: Length of in-hospital stay for ACS patients, UA 119
Figure 39: Length of in-hospital stay for ACS patients, NSTEMI 119
Figure 40: Length of in-hospital stay for ACS patients, STEMI 120
Figure 41: Percentage of all ACS patients who have been transferred or referred to hospitals and transferred from hospitals for further PCI or CABG or other treatment 121
Figure 42: Distribution of troponin test 122
Figure 43: Distribution of Echo and Nuclear perfusion tests 124
Figure 44: Distribution of CT and MRI tests 126
Figure 45: Distribution of stress test 127
Figure 46: Distribution of IVUS (%) in angiography cases only 128
Figure 47: Distribution of thrombolytic therapy in all ACS patients and in patients presented with ST-segment elevation 129
Figure 48: Country distribution of thrombolytic therapy in patients presented with ST-segment elevation only 130
Figure 49: Country distribution of success rate of thrombolytic therapy in patients presented with ST-segment elevation 131
Figure 50: Specific thrombolytic molecules use distribution in 5 European countries 132
Figure 51: % of all ACS patients receiving Diagnostic Angiography test then PCI and then Stenting 133
Figure 52: Door to PCI time, percentage of patients who received PCI <12h from hospital admission vs. >12h from hospital admission 134
Figure 53: Distribution of STENT implantations by type 135
Figure 54: % of CABG 135
Figure 55: Early reperfusion therapy (< 12 h after onset of symptoms) distribution in STEMI patients 136
Figure 56: Use of unfractionated heparins in the treatment of ACS patients 137
Figure 57: Use of low molecular weight heparins (LMWH) in the treatment of ACS patients 139
Figure 58: Use of COX-1 Inhibitors (aspirin) in the treatment of ACS patients 140
Figure 59: Use of ADP receptor antagonists in the treatment of ACS patients 141
Figure 60: Use of GPIIb/IIIa receptor inhibitors in the treatment of ACS patients 143
Figure 61: Use of nitrates in the treatment of ACS patients 144
Figure 62: Use of betablockers in the treatment of ACS patients 146
Figure 63: Use of ACE inhibitors in the treatment of ACS patients 148