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Vascular and Endovascular Surgery E-Book

Vascular and Endovascular Surgery E-Book

Jonathan D Beard | Peter A. Gaines | Ian Loftus

(2013)

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Book Details

Abstract

Vascular and Endovascular Surgery meets the needs of surgeons in higher training and practising consultants for a contemporary and evidence-based account of this sub-specialty that is relevant to their general surgical practice. It is a practical reference source incorporating the most current information on recent developments, management issues and operative procedures. The text is thoroughly referenced and supported by evidence-based recommendations wherever possible, distinguishing between strong evidence to support a conclusion, and evidence suggesting that a recommendation can be reached on the balance of probabilities.

This is a title in the Companion to Specialist Surgical Practice series whose eight volumes are an established and highly regarded source of information for the specialist general surgeon.

  • The Companion to Specialist Surgical Practice series provides a current and concise summary of the key topics within each major surgical sub-specialty.
  • Each volume highlights evidence-based practice both in the text and within the extensive list of references at the end of every chapter.
  • An expanded authorship team across the series includes additional European and World experts with an increased emphasis on global practice.
  • The contents of the series have been extensively revised in line with recently published evidence.
  • The revision of the content reflects the continued move towards non-invasive imaging, medical therapy and endovascular techniques, culminating in a new chapter on Future Developments.
  • Many of the chapters reflect the collaborative nature of a modern vascular service and are co-authored by a vascular surgeon and a vascular radiologist.
  • The authorship team has been expanded with input from vascular nursing and rehabilitation experts.

Table of Contents

Section Title Page Action Price
Front Cover Cover
Vascular and Endovascular Surgery: A COMPANION TO SPECIALIST SURGICAL PRACTICE iii
Copyright iv
Contents v
Contributors vii
Series Editors' preface xi
Editors' preface xiii
Evidence-based practice in surgery xv
Further reading xvii
General vascular xvii
Rare vascular disorders xvii
Imaging xvii
Specialist xvii
Websites xvii
Chapter 1: Epidemiology and risk factor management of peripheral arterial disease 1
Introduction 1
Epidemiology of PAD 1
Investigative techniques for epidemiological screening 2
Prevalence and incidence of PAD 2
Natural history of PAD: cardiovascular and lower limb outcomes 3
Asymptomatic disease 3
Intermittent claudication 3
Critical limb ischaemia 4
The Reduction of Atherothrombosis for Continued Health (REACH) registry 4
Epidemiological risk factors for PAD and randomised trials of disease-modifying therapy for secondary prevention 4
CV risk factors in general 4
Risk factors for PAD 4
Age and gender 5
Cigarette smoking 5
Diabetes 6
Blood pressure (BP) 6
Renin–angiotensin–aldosterone system blockade 7
Serum lipids 7
Evidence for dietary control or supplementation 9
Antiplatelet therapy 11
Exercise therapy 11
Conclusions 12
References 13
Chapter 2: Assessment of chronic lower limb ischaemia 16
Introduction 16
Intermittent claudication (IC) 16
Critical ischaemia 17
Rare causes of ischaemia 18
Persistent sciatic artery 18
Cystic adventitial disease (CAD) 19
Popliteal artery entrapment 19
Fibromuscular dysplasia (FMD) 20
Buerger's disease 20
History and examination 20
History 20
Examination 20
Exercise challenge 21
ABPI measurement using a hand-held Doppler device 22
Toe pressures 22
The ischaemic angle 23
Risk factors 23
Vascular laboratory 23
Waveform assessment and segmental pressures 23
Laser Doppler and transcutaneous oximetry 24
Duplex ultrasound (DUS) 25
Assessment of suprainguinal arteries 25
Assessment of infrainguinal arteries 26
Radiological investigations 27
Contrast media 27
Magnetic resonance angiography (MRA) 29
Chapter 3: Medical treatment of chronic lower limb ischaemia 36
Introduction 36
PAD diagnosis and screening 37
Modifying cardiovascular risk 38
Medical treatments for symptomatic PAD 39
Exercise 39
Drug treatment 40
Vasoactive drugs 40
Prostanoids 40
Angiogenesis 41
Gene therapy 41
Cell therapy 41
Spinal cord stimulation 41
Lumbar sympathectomy 41
Intermittent pneumatic compression 41
Conclusions 41
References 42
Chapter 4: Intervention for chronic lower limb ischaemia 45
Introduction 45
Patient selection 45
Cost-effectiveness 46
TASC recommendations 47
Suprainguinal endovascular intervention 48
Abdominal aorta 48
Iliac arteries 48
When is an iliac lesion significant? 49
Who should have an angioplasty or a stent? 49
Iliac stenoses 50
Iliac occlusions 51
Complications 51
Bleeding and pseudoaneurysm development 51
Arterial rupture 51
Embolisation 51
Stent-related complications 51
Suprainguinal open surgical intervention 51
Aorto-bifemoral bypass 54
Axillo-bifemoral bypass 54
Unilateral iliofemoral bypass 55
Iliofemoral crossover 56
Femorofemoral crossover 56
Femoral endarterectomy and profundaplasty 56
Infrainguinal reconstruction 57
Choice of graft material 59
In situ versus reversed vein 60
Prosthetic grafts 60
Graft surveillance 61
Infrainguinal endovascular intervention 61
Femoropopliteal angioplasty 61
Subintimal angioplasty 61
Femoropopliteal stents 61
Drug-eluting stents/balloons 63
Covered stent grafts 64
Crural artery intervention 65
Infrainguinal bypass versus angioplasty 65
Non-interventional treatment for CLI 66
Iloprost 66
Spinal cord stimulation 66
Sympathectomy 66
Calf and foot compression 66
References 67
Chapter 5: The diabetic foot 73
Introduction 73
Epidemiology 73
Aetiology of foot ulceration 74
Diabetic neuropathy 74
Peripheral vascular disease 75
Biomechanical aspects 78
Other risk factors 78
The pathway to ulceration 79
Management 79
The ‘at-risk’ foot 79
Ulcer management 80
Neuropathic ulcers 80
Ischaemic and neuroischaemic ulcers 81
Infection 83
Larva debridement therapy 85
Medical problems on the surgical ward 85
Charcot neuroarthropathy 85
References 87
Chapter 6: Amputation, rehabilitation and prosthetic developments 90
Introduction 90
Epidemiology 90
Indications for amputation 91
Level selection 91
Surgical considerations 92
Transfemoral amputation 93
Through-knee amputation 93
Transtibial amputation 93
Foot amputation 94
Rehabilitation 94
Planning 95
Stump management 95
Pain management 95
Early postoperative rehabilitation 96
Primary prosthetic rehabilitation 96
Sport activities for amputees 96
Prostheses 97
Prosthetic developments 97
Rehabilitation for the bariatric patient 99
References 100
Chapter 7: Revision vascular surgery 102
Introduction 102
Graft occlusion 102
Factors influencing graft occlusion 102
Local factors 102
General factors 103
Prevention of graft thrombosis 104
Management of graft stenosis (the failing graft) 104
Management of the failed graft 104
Role of thrombolysis 104
Suprainguinal graft thrombosis 105
Infrainguinal graft thrombosis 106
Graft infection 106
Causes 106
Prevention 107
Presentation 107
Bacteriology 107
Diagnosis 108
Management 109
General principles 109
Infrarenal aortic graft infection 109
Graft aneurysms 111
True aneurysms 111
False aneurysms 111
Carotid artery 114
Infection 114
Aneurysm formation 114
Revision after CAS 114
Revision surgery after EVAR 115
Revision after thoracic endovascular aortic repair (TEVAR) 116
Aortobronchial fistula 116
Aorto-oesophageal fistula 116
Infection 116
References 117
Chapter 8: Management of acute lower limb ischaemia 122
Introduction 122
Aetiology 122
Embolism 122
Atheroembolism 122
Thrombosis 123
Other causes 124
Recent changes 126
Clinical features 126
Initial management 126
Revascularisation 127
Irreversible (category III) leg ischaemia 127
Immediately threatened (category IIb ischaemia) 128
Threatened (category IIa ischaemia)/viable (category I ischaemia) 128
Choice between surgery and thrombolysis: the evidence 129
Peripheral arterial thrombolysis 129
Contraindications (Box 8.2) 129
Technique 130
Percutaneous thrombectomy devices 133
Complications 133
Outcome 133
Surgical management 134
Balloon catheter embolectomy 135
Completion angiography 135
Failed embolectomy 136
Further management 136
Overall prognosis 137
Conclusions 137
References 138
Chapter 9: Vascular trauma 140
Introduction 140
Mechanism of injury 140
Blunt trauma 140
Penetrating trauma 140
Sequelae of vascular injuries 140
Clinical assessment 142
History 142
Examination 142
Diagnosis 142
Resuscitation and initial management 142
Special investigations 143
Plain radiography 143
Arteriography 143
Ultrasound 143
Axial imaging 143
General principles of management of vascular injury 143
Venous injuries 144
Endovascular management of vascular trauma 145
Cervical vascular injuries 146
Carotid artery injuries 146
Mechanism 146
Clinical signs 146
Diagnosis 147
Management 147
Operative technique 147
Vertebral artery injuries 148
Endovascular management of cervical injuries 148
Thoracic vascular injuries 148
Clinical presentation and initial management 148
Diagnostic studies 149
Chest radiography 149
Angiography 149
Other imaging modalities 149
Treatment 149
Endovascular repair 150
Surgical repair 150
Abdominal vascular injuries 150
Diagnosis 150
Management 150
Aortic injury 151
Iliac injury 151
Visceral artery injury 151
Renal artery injury 152
Inferior vena cava injury 152
Pelvic vascular injury 152
Extremity vascular trauma 152
Diagnosis 152
General principles of management 152
Vascular injuries to the upper extremity (Fig. 9.14) 154
Subclavian and axillary injuries 154
Vascular injuries to the lower limb 155
Femoral vascular injuries 155
Popliteal vascular injury 155
References 156
Chapter 10: Extracranial cerebrovascular disease 160
Introduction 160
Aetiology and risk factors 160
Large-vessel thromboembolism 160
Small-vessel disease 160
Cardiogenic brain embolism 160
Haematological disorders 161
Non-atheromatous carotid diseases 161
Fibromuscular dysplasia (FMD) 161
Arteritis (see also Chapter 12) 161
Carotid aneurysm 162
Carotid dissection 162
Carotid body tumour 163
Presentation of carotid disease 163
Asymptomatic cerebrovascular disease 163
Symptomatic cerebrovascular disease 164
Carotid territory 164
Vertebrobasilar 165
Non-hemispheric 165
Investigation of carotid disease 165
Duplex ultrasound 166
Catheter angiography 166
Magnetic resonance angiography 167
Computed tomography angiography (CTA) 168
Management of cerebrovascular disease 168
‘Best medical therapy’ 168
Surgical management of carotid disease 170
Symptomatic carotid artery disease 170
Asymptomatic carotid artery disease 173
CEA/CAS and coronary bypass 174
Emergency CEA 175
Vertebral artery revascularisation 175
Surgical management of carotid disease – carotid endarterectomy 175
Anaesthesia 175
Technique 176
Patch or primary closure? 176
Routine, selective or never shunt? 176
Perioperative monitoring 176
Completion assessment 177
Operative complications 177
Cranial nerve injuries 177
Wound complications 177
Perioperative stroke 177
Long-term follow-up and re-stenosis 178
Patch infection 178
Endovascular treatment of carotid disease 179
Results of CAS 179
Ongoing controversies 179
Is CEA or CAS safer in the hyperacute period after onset of symptoms? 179
Importance of perioperative MI 180
A surgeon's perspective 180
An interventionist's perspective 180
New ischaemic lesions on MRI 181
Assessing suitability for CAS 181
Dual antiplatelet therapy 182
CAS technique 182
Embolic protection devices 183
Distal balloon occlusion 183
Distal filters 183
Flow reversal/flow arrest (endovascular clamping) 183
Does stent design influence outcome? 184
Periprocedural haemodynamic problems 184
Haemodynamic depression 184
Hyperperfusion 185
Post-CAS care 185
Achievement and maintenance of competence 185
References 186
Chapter 11: Vascular disorders of the upper limb 190
Introduction 190
Clinical examination 190
Occlusive disease 190
Brachiocephalic artery 190
Aorto-brachiocephalic bypass 191
Brachiocephalic endarterectomy 191
Endovascular treatment 191
Subclavian artery 192
Carotid–subclavian bypass 192
Carotid transposition 192
Crossover grafts 193
Endovascular treatment 195
Upper arm arteries 195
Lower arm and hand arteries 195
Aneurysmal disease 196
Upper arm artery aneurysms 197
Lower arm and hand artery aneurysms 197
Ulnar artery aneurysm or hypothenar hammer syndrome 197
Upper limb embolism 198
Other causes of acute ischaemia 198
Thoracic outlet syndrome 199
Neurogenic thoracic outlet compression syndrome (N-TOCS) 199
Diagnosis 199
Treatment 199
Transaxillary resection of first rib 199
Arterial thoracic outlet compression syndrome 201
Surgical management 201
Combined supraclavicular and infraclavicular approach 201
Subclavian–axillary vein thrombosis 203
Primary SVT 204
Diagnosis 204
Treatment 204
Secondary SVT 205
References 206
Chapter 12: Primary and secondary vasospastic disorders (Raynaud's phenomenon) and vasculitis 210
Introduction 210
Raynaud's phenomenon 210
Pathophysiology 212
Neurogenic 212
Interactions between blood and blood vessel walls 212
Inflammatory and immunological mechanisms 212
Genetic factors 212
Clinical features 212
Investigations 213
Management 214
General measures 214
Drug therapy 214
Calcium channel blockers 214
Other vasodilators 215
Prostaglandins 215
Other drugs 216
Sympathectomy 216
Conclusion 216
Connective tissue disease 216
Vasculitis 217
Takayasu's arteritis 218
Buerger's disease (thromboangiitis obliterans) 218
Giant cell arteritis 219
Polyarteritis nodosa 220
Wegener's granulomatosis 221
Cutaneous vasculitis/small-vessel vasculitis 221
Idiopathic cutaneous vasculitis 221
Necrotising vasculitis associated with infections, drugs or CTD 222
Cutaneous vasculitis as a manifestation of systemic disease 222
Conclusion 222
References 223
Chapter 13: Peripheral and abdominal aortic aneurysms 226
Definition of an aneurysm 226
Prevalence of arterial aneurysms 226
Pathogenesis of aortic aneurysms 226
Infrarenal abdominal aortic aneurysms 227
Symptomatic and ruptured AAAs 227
Inflammatory abdominal aortic aneurysms (IAAAs) 227
Population screening for AAAs 227
Principles of AAA management 228
Surveillance of patients with small aneurysms 228
AAA repair 228
Investigation of the patient with known AAA 229
Preprocedural imaging 229
Elective open AAA repair 229
Minimally invasive open AAA repair 230
Emergency open AAA repair 230
Outcome following open surgical AAA repair 230
Endovascular AAA repair (EVAR) 231
Indications and eligibility for EVAR 231
EVAR devices 231
Patient assessment and EVAR technique 232
EVAR-related complications and device failure 232
Endoleak 232
Graft migration and dislocation 233
Kinking and occlusion 233
Other EVAR-related complications 233
Surveillance after EVAR 234
Outcomes after EVAR 235
The future of EVAR 237
Infected aneurysms 238
True mycotic aneurysms 238
Microbial aneurysmal arteritis 239
Clinical features and management principles of infected aneurysms 239
Peripheral aneurysms 239
Iliac aneurysms 239
Common femoral aneurysms 239
True femoral aneurysms 240
False femoral aneurysms 240
Popliteal artery aneurysms 241
References 242
Chapter 14: Thoracic and thoraco-abdominal aortic disease 246
Introduction 246
Imaging of the thoracic aorta 246
Thoracic aortic aneurysms (TAAs) 247
Classification and aetiology 247
Incidence and clinical presentation 247
Indications for treatment 247
Technique of surgical repair 247
Endovascular repair of thoracic aneurysms 247
Management of the spinal cord during endovascular thoracic procedures 249
Outcome of treatment 249
Recommendations for practice 249
Thoraco-abdominal aortic aneurysms (TAAAs) 249
Surgical management 250
Adjunctive surgical techniques 250
Results of surgical repair of thoraco-abdominal aneurysms 251
Hybrid visceral revascularisation and endovascular repair of thoraco-abdominal aortic aneurysms 251
Total endovascular repair of thoraco-abdominal aortic aneurysms 253
Recommendations for practice 254
Thoracic dissection and acute aortic syndrome 254
Pathology and classification 254
Conventional management of acute aortic dissection 255
Endovascular management of acute type B thoracic dissection 255
Endovascular treatment of chronic dissections 257
Recommendations for practice 257
Traumatic aortic injury (TAI) 257
Recommendations for practice 258
References 258
Chapter 15: Renal and intestinal vascular disease 262
Renal artery disease 262
Fibromuscular dysplasia (FMD) 262
Arteritis 262
Atherosclerotic renal vascular disease 263
Definition and pathology 263
Pathophysiology 263
Renal function 263
Hypertension 263
Diagnosis and presentation 264
ARVD and cardiovascular disease 264
Management options 264
Medical therapy 264
Antihypertensive therapy 264
Endovascular treatment of ARVD 264
Imaging and work-up 265
Procedure (Fig. 15.1c–e) 265
Complications 266
Results of angioplasty and stenting 266
Stenting versus PTA 266
Re-stenosis and drug-eluting stents 267
Surgical treatment 267
Renal artery denervation 268
Intestinal vascular disease 269
Intestinal ischaemia 270
Acute mesenteric ischaemia (AMI) 270
Aetiology and incidence 270
Pathophysiology 270
Diagnosis and treatment 270
Mesenteric venous thrombosis 271
Non-occlusive mesenteric thrombosis 271
Chronic mesenteric ischaemia (CMI) 271
Aetiology and incidence 271
Diagnosis 271
Surgical intervention 272
Endovascular options 273
Coeliac axis compression syndrome 274
Visceral aneurysms 274
Aetiology and incidence 274
Diagnosis and treatment 274
Acknowledgements 275
References 275
Chapter 16: Central venous and dialysis access 279
Introduction 279
Central venous access 279
Indications 279
Methods 279
Complications 279
Temporary dialysis access 280
Methods 280
Complications of CVCs 280
Insertion 280
Catheter dysfunction 280
Catheter-locking solutions 280
Catheter lumen thrombosis 281
Central vein thrombosis 281
Fibrin sheaths 281
Catheter-related infection 281
Permanent dialysis access 282
Access planning 282
Preoperative assessment 282
Duplex ultrasound 283
Venography 283
Primary access 283
Secondary and tertiary access 284
Factors affecting access patency 285
Access failure 286
Failure to mature 286
Stenosis and thrombosis 286
Prevention of access failure 286
Access surveillance 286
Access salvage 287
AVF stenosis 287
AVG stenosis 288
AVF and AVG thrombosis 288
Other access complications 288
Infection 288
Haemorrhage 289
Steal 289
Carpal tunnel syndrome 290
Cardiac failure 290
Venous hypertension and central vein obstruction 291
Aneurysm 291
Cannulation 292
Access in children 292
References 293
Chapter 17: Varicose veins 298
Introduction 298
Pathophysiology 298
Normal venous function 298
Chronic venous hypertension 298
Varicose veins 298
Epidemiology and natural history 299
Clinical presentation 300
Thread veins and reticular veins (CEAP C1) 300
Varicose veins (CEAP C2) 300
Oedema and skin changes (CEAP C3–C4) 300
Chronic venous ulceration (CEAP C5–C6) 301
Clinical assessment 301
History 301
Patient examination 301
Venous investigations 302
Hand-held Doppler and other bedside tests 302
Duplex ultrasound scanning 302
Other investigations 302
Treatment 302
Conservative options, drugs and compression therapy 303
Conservative options 303
Pharmacotherapy 303
Compression stockings 303
Principles of surgical and endovenous intervention 304
Pre-procedure marking 304
Marking the GSV or SSV 304
Marking of varicosities 304
Informed consent 304
Traditional surgery 304
Setting and anaesthesia 304
Great saphenous vein surgery 304
Small saphenous vein surgery 305
Redo varicose vein surgery 305
Complications 305
Endovenous thermal ablation 306
Setting and anaesthesia 306
Summary of technique 306
Endovenous laser ablation (EVLA) 307
Radiofrequency ablation (RFA) 307
Complications 307
Ultrasound-guided foam sclerotherapy (UGFS) 308
Setting and anaesthesia 308
Technique 308
Complications 308
Treatment of incompetent perforating veins 309
Management of varicosities 309
Other treatment options 310
Preserving the saphenous vein 310
Novel endovenous therapies 310
Evidence for traditional and endovenous intervention 310
Traditional surgery 310
Endovenous thermal ablation 311
Ultrasound-guided foam sclerotherapy 311
Deciding between treatment modalities 311
Cost-effectiveness of treatments 311
Atypical varicose veins 312
Vulval and pelvic varices 312
Congenital causes of varicose veins 312
Conclusions 312
References 313
Chapter 18: Chronic leg swelling 316
Chronic venous insufficiency (CVI) 316
Clinical features 316
Swelling 316
Skin changes 316
Ulceration 316
Varicose veins 316
Pain 316
Epidemiology 317
Aetiology 317
Macrocirculation 317
Deep and superficial reflux 317
Perforating vein reflux 317
Microcirculation 318
Classification 318
Investigation 318
Hand-held Doppler 319
Duplex scanning 319
Venography 319
Functional measurements 319
Ambulatory venous pressure measurement 319
Plethysmography 319
Treatment 319
General measures 319
Graduated elastic compression 320
Intermittent pneumatic compression 320
Laser and electromagnetic therapy 320
Pharmacotherapy 320
Dressings 320
Emollients 321
Oxpentifylline (pentoxifylline) 321
Nutrition 321
Superficial venous intervention 321
Superficial venous surgery 321
Perforating vein surgery 321
Deep venous reconstruction 321
Venous bypass 321
Skin grafting 322
Endovascular management of venous outflow obstruction 322
Preventing the post-thrombotic limb 322
Summary 323
Dependency and inactivity 323
Lymphoedema 323
Aetiology 323
Primary 323
Secondary 324
Presentation 324
History 324
Examination 325
Clinical staging 325
Investigation 325
Duplex ultrasonography 326
Lymphangioscintigraphy (isotope lymphography) 326
Computed tomography 326
Magnetic resonance imaging (MRI) 326
Interstitial magnetic resonance lymphangiography 326
Fluorescence microlymphangiography (FML) 326
Contrast lymphangiography 327
Treatment 327
General measures 327
Manual lymphatic drainage 327
Graduated elastic compression 327
Intermittent pneumatic compression (IPC) 327
Thermal treatment 327
Complex decongestive physiotherapy (complex physical therapy) 327
Prevention of infection 328
Drugs 328
Surgical treatments 328
Debulking operations 328
Bypass procedures 328
References 329
Chapter 19: The acutely swollen leg 334
Introduction 334
Pathophysiology of oedema 334
Medical history 334
Physical examination 335
Differential diagnosis 335
Musculotendinous rupture 335
Baker's cyst 335
Cellulitis and erysipelas 335
Necrotising fasciitis 335
Lymphoedema 336
Bilateral swelling 336
Deep venous thrombosis 336
Pathophysiology of DVT 336
Clinical decision rules 336
Imaging techniques 337
Treatment of DVT 338
Prognosis 339
Iliofemoral deep vein thrombosis 339
Post-thrombotic syndrome 339
Catheter-directed thrombolysis 340
New treatment modalities 341
EKOS endowave 341
Trellis-8 342
Angiojet 342
The future 342
References 343
Chapter 20: Vascular anomalies 346
Introduction 346
Vascular tumours 346
Haemangioma of infancy 346
Infantile haemangioma 346
Subglottic haemangiomata 347
Parotid gland haemangiomata 347
PHACE syndrome2 347
Diagnosis and imaging 347
Management of haemangiomata of infancy 347
Congenital haemangioma4 348
Other vascular tumours 348
Vascular malformations 348
Classification 348
Low-flow malformations 348
Capillary malformations 348
Salmon patch (naevus simplex; erythema nuchae) 348
Port-wine stains (naevus flameus) 349
Venous malformations 349
Imaging 349
Management of venous malformations 350
Lymphatic malformations 350
Management9 350
High-flow malformations 350
Imaging 351
Management 351
Embolisation 351
Embolisation and surgery 352
Results 353
Conclusions 353
References 353
Chapter 21: Future developments 355
Introduction 355
Cholesterol-lowering and antiplatelet therapy 355
Novel cholesterol-lowering secondary prevention therapies 355
Increasing high-density lipoprotein (HDL) 355
Cholesterol ester transfer protein inhibitors 355
Niacin 356
Apolipoprotein A-I and mimetic peptides 357
Summary: therapy to increase levels of HDL cholesterol 357
Lipoprotein metabolism and inflammatory response 357
Secretory phospholipase A2 inhibitors 358
Lipoprotein-associated phospholipase A2 inhibitors 358
Novel antiplatelet agents 358
Thrombin receptor antagonists: protease-activated receptor 1 (PAR-1) 359
Vorapaxar: phase III trials 359
P2Y12 receptor antagonists 359
EP3 receptor antagonists 359
Summary: novel antiplatelet agents 359
Angiogenesis 360
Target genes in use for gene therapy in peripheral arterial disease 361
Gene therapy vectors 361
Non-viral methods 361
Viral methods 361
Delivery methods of vectors 361
Vascular endothelial growth factor (VEGF) 361
Phase I clinical trials 361
Index 371