Yearbook of Vascular and Endovascular Surgery-3 (2021) R Sekhar
Page numbers followed by b refer to box, f refer to figure, fc refer to flowchart, and t refer to table.
Abdomen 178
venous duplex of 58
Abdominal pain, causes of 16
Adjunctive modalities 78
Adjunctive therapy 80f
Advanced trauma life support principles 195
Adventitia 142
Aesculus hippocastanum 37
Air embolization 199
Albumin 132
Alcoholism 93
Aldosteronism 147, 148
ALN filter 216f
Alpha-benzopyrone 31, 34, 35
Alternative therapeutic method 265
Amino acids 132
Amputation 66
Anaphylaxis 180
end-to-side distal 161
occlusion 93
revision of 107
Anastomotic pseudoaneurysms 185
Anastomotic stenosis 103f
Aneurysm 17, 101, 228, 257
etiology of 239
infected 238
primary 228
rupture 239
sac 260
tissue 230
Angel catheter 222
Angioplasty, primary 21
Angiosome 279, 280
affected 279
concept of 279
applications of 282
functional 280
Angiotensin receptor blockers 146, 151
Angiotensin-converting enzyme inhibitor 146, 151
Ankle arteries 282f
Ankle-brachial index 68
Antegrade celiac bypass 17
Antegrade femoral access 250f
Anterior tibial artery 280
puncture 252f
Anthocyans 31
Antibiotic 132, 240
impregnation 237
therapy 234
Antibiotic-resistant organisms 240
Anticoagulants 6
revascularization 2t
bleeding complications of 4t
complications of 206
expectations from 3t
therapy 1, 273, 274t
Antideoxyribonuclease 128
Antigen-antibody reaction 124
Antihypertensive drugs 153
Antihypertensive medication 151
Antihypertensive therapy 151
Anti-inflammatory effects 32
Antimetabolites 139
Antioxidants, circulating 78
Antioxidative properties 32
Antiplatelet 6
agents 9, 12
and anticoagulant therapies, strategies of 11
vascular evaluation 5
Antiseptics 40
Antithrombotic therapies 6, 7fc
Antithrombotic treatment 1fc, 7t
Antithrombotic trialists’ collaboration 2
Anxiety 87
Aorta 142
abdominal 130, 131, 175, 239
arch of 130
ascending 130
calcific 134
descending thoracic 130, 193f, 200, 202
infrarenal 17
mechanisms of injury to 190
supraceliac 17
surgery for ascending 198
thoracic 125, 239
Aortic anastomosis 161
Aortic aneurysm
etiology of infected 231f
infected 228, 236f
managing infected 228
risk factors for infected 228
signs of infected 233f
size 134
treat infected 235fc
Aortic arch 126
Aortic bifurcation 132f
Aortic crus level 132
Aortic injury 193f
classification of 191
Aortic isthmus 133f
Aortic patch plasty 19f
Aortic root 190
Aortic stenosis, correction of 19f
Aortic tears, complex 200
Aortoaortic shun 199f
Aortobifemoral bypass 19
Aortoduodenal fistula 231
Aortoenteric fistula 236f
Aortography 194
Aortorenal bypass 157, 161
Arch injuries, surgery for 198
Arterial access, duplex guidance for 250f
Arterial anastomotic sites 185
Arterial aneurysms, primary infected 228
Arterial obstruction 129
Arterial segment, focal dilatation of 228
Arterial territories 174f
Arterial tissue 228
Arterialized vein, stenosis of 103f
Arterioles 153
Arteriotomy 23
Arteriovenous fistula 102, 104f, 118, 232, 249
Arteriovenous graft 102
stenosis 114
Arteriovenous malformation 251
embolization 257f
high-flow 256f
dysplasia 21
obliterating 284
antegrade brachial 265f
aortic 231
autologous hypogastric 161
axillary 183
brachial 183
carotid 130
cavernous 84
common carotid 130
coronary 128, 142
dorsal penile 90
dorsalis pedis 280
gastroduodenal 162
hypothermic branch renal 163
infected left femoral 187f
inferior epigastric 90
inferior mesenteric 16
internal carotid 131f
intrarenal 153
lateral plantar 280
left renal 135f, 137
medial plantar 280
panbrachiocephalic 129f
peroneal 280
posterior tibial 280
pulmonary 128
reconstructive procedures 160
viscerorenal 126
Arthritis 125
Aseptic precautions 179
Aspergillus 230
Aspirin 3, 6, 10
effect of 3
Assisted reproductive technology 269
Atherosclerosis 16, 126t, 229, 284
absence of significant 229
prevalence of 142
Atherosclerotic disease 151, 155
Atherosclerotic lesions 142
Atherosclerotic origin, complications of 3
Atherosclerotic plaque 153, 229, 230
Atherosclerotic renal artery stenosis 151
Autoimmune disorder 124
Autologous graft material 235
Axillofemoral bypass 237
Bacteremic seeding 229
Baker's cyst 96
angioplasty 105
maceration 257
Bariatric surgery 211
Barotrauma 111
Basilic vein 103f
transposition 109, 110
Below-knee amputation 74f
Beta-blockers 156
Betamethasone 40
Betrixaban plus aspirin 9
Biodegradable polymer wraps 118
Biofilms 67
Bleeding, types of 4
Blindness 66
flow, decreased 147
pressure 141, 151, 166
products 132
sinusoids 84
Bloodstream infections, catheter-related 223
Blunt aortic injuries 191
Blunt traumatic aortic injuries 199f, 202
Body mass index 212
Bovine heparin 180
Bovine pericardial patch 180
Bovine pericardium patch angioplasty 108f
Bridge therapy 188, 240
Brucella 231
Buck's fascia, compartment of 84
Burkholderia 231
Bypass thrombosis 8
Cadexomer iodine 40
alginate 70, 73
dressing 73f
dobesilate 37
Campylobacter 231
Candida 230
Capillary endothelium 57
Captopril scintigraphy 148
Carbon dressing 75, 75f
Cardiovascular risk reduction 152
Carotidynia 125
Catastrophic atheroembolism 125
double-curve 21
venography 98
Ceftriaxone 234, 240
Celect filter 217, 217f
Celect platinum filters 213
Celiac trunk stenting 23
Centella asiatica 37
triterpenic fraction of 37
Central vein
catheter 222f
post venoplasty 117f
stenosis 116, 117f
stenotic lesion balloon angioplasty 117f
Cephalic arch stenosis 109, 111f, 112
lesions 114
open surgery for 113
Cephalic arch stenting 111f
Cephalic vein 112f
transposition 113
technique 113f
Cerebrospinal fluid 136
Cesarean section, thromboprophylaxis after 269
Channel blockers 156
Charcoal 71
Chest radiography 192
Cholecystectomy 229
Chronic complex wound, management of 75
Chronic mesenteric ischemia, anatomical basis of 15
Chronic pelvic pain, differential diagnosis of 61
Chronic venous
disease 44
management of 39
disorder 28, 29t, 30
medical management of 43
insufficiency 28, 29f
Cilostazol 6
Citationid 213, 217
Citrus fruits 42
Clamp-and-sew technique 198
Clavicular trauma 182f
Clopidogrel 3, 6, 8, 10
plus aspirin 6
Cobalt-chromium alloy 213
Collagen dressing 76, 77f
Collateral blood supply 280
Collateral circulation, development of 125
Colorectal surgery 229
Combined intracavernosal injection 87
Compression therapy 40
Compression ultrasonography 271
Computed tomography angiography 148, 150
Concomitant injuries 195
Concomitant popliteal artery entrapment 98
Congestion-fibrosis syndrome 54
Congestive cardiac failure 146
Conservative treatment 98
Contralateral kidney 144, 146
Coronary heart disease 146
high risk of 1
Corpora cavernosa 84
Corynebacterium 230
Coumarin 30, 31
Coxiella burnetii 230
C-reactive protein 128
Critical limb ischemia 11, 279, 283
Critical stenosis 15
Cross-sectional computed tomography 60
Cryptococcus 230
Cutting balloon 106
angioplasty 107, 111, 118
Cyclic adenosine monophosphate 38
Decompensation, acute 154
Deep dorsal vein 90
Deep vein thrombosis 36, 95, 205, 206, 209, 210, 265, 267, 271, 271fc
treatment of 272
Denali filter 213, 216, 216f
Depression 87
Diabetes 87
mellitus 66, 93
Diabetic arterial disease 280
Diabetic foot 76
neuroischemic 283
ulcer 66
Diabetic population, rate of 283
Diabetic subjects, chronic 284
Diaphragm 190
Diarrhea 16
Digital subtraction angiography 234
Dihydroxyethylrutosides 36
Direct arteriovenous graft 261f
Direct femoropopliteal graft puncture 262
Direct graft puncture 260f
Direct sac puncture 264f
Disease process, reactivation of 125
Distal femur 95
Dorsal artery exposure 90
Downstream factors 101
Dressing 40, 41
advanced 76
antimicrobial 67
multifunction 71, 76, 77f
occlusive 42
types of 69, 70t
Drug-eluting balloon 118
angioplasty 107
Edema, postoperative 93
Ejaculation, premature 86
Emergency thoracotomy 201
End-arterial occlusive disease 284
End-diastolic velocity 16
Endocrine neoplasia, multiple 148
Endoleak 264f
Endothelial cells 32
Endotracheal tube, double-lumen 200
Endovascular intervention 24, 196
Endovascular procedure 116
planning 21
Endovascular techniques 181, 240, 282
role of 237
Endovascular therapies 6, 155, 180, 237, 240
Endovascular treatment 20, 24, 62
role of 154
Enzymatic agents 41
Epidermal growth factor 41
Epigastric artery, harvesting inferior 90
Erectile dysfunction 83, 86, 88
history 86
severity of 87
Erectile function, index of 87
Erection physiology 86f
Erythema 271
Erythrocyte sedimentation rate 128, 231
Escherichia coli 76, 231
Esophagus 194
Excretory dysfunction 157
Extra-anatomic bypass 237
Extracellular polysaccharide 67
Far-infrared electromagnetic radiation 117
Female varicocele 54
Femoral artery 176, 187f, 200
access, superficial 252f
infected aneurysms 231
pseudoaneurysm 178f, 180
stent puncture 252f
Femoral vein, common 60
Femoral-popliteal deep vein 237
Femorodistal reconstructions 10
Femorofemoral bypass 200
Femoropopliteal bypass graft, left 185f
Femoropopliteal steno-occlusive disease 126
Fibromuscular dysplasia 21, 141, 142, 157
Fibroplasia, medial 143
Fibrosis, stage of 125
Fibrotic nonyielding lesions 129
Film dressing 72, 72f
data 215
design 213
fracture 216
migration 216, 218
penetration 215
placement 205
retrieval 218
techniques 221
Flank exposure 159
Flash pulmonary edema 127, 146, 154
Flavonoids 3032, 34
Fluocinolone 40
Fluoroquinolone 234, 240
Fluoroscopic guidance 266
sac puncture 263f
Foam 71, 73
dressing 74f
with silicone 73
dressing 74f
arteries 282f
infection 68
classification 68t
Free oxygen radicals 145
Fungus vegetations 228
Furlow-Fisher technique 92
Fusiform dilatation 193
Gadolinium 150
partial 9
warrants 279
Giant aneurysm 160f
Glans hyperemia 93
Glasgow coma scale 211
Glomerular filtration rate 145, 151
Glucocorticoid therapy, chronic 228
Glycosaminoglycan 39
failure, high risk of 4
patency of 12t
Gram stain 232
Gravid uterus 268f
Great saphenous vein 28, 237
Growth factors 41
Günther tulip filter 213
Haemophilus influenzae 231
Harikrishna periwound skin classification 67t
Hauri technique 91, 92f
Heart 194, 221
bypass, left 199
disease 66
valve, mechanical 270, 273
Hematoma 93, 175f, 198, 215
groin 175f
intramural 194
periaortic 194
Hemodialysis 249
chronic 260
Hemodynamic blood flow analysis 88
Hemodynamic changes 56, 56b
Hemorrhage 206
intraoperative 136
venous 192
Hemostasis 132
allergy, anticoagulation in 274
lower dose of 196
therapy 272
Hepatorenal bypass 162
Hesperidin methylchalcone 44
High-pressure balloon 105, 106f
Hindfoot angiosomes 280
Honey dressing 76
Horse chestnut seed extract 45
Human keratinocytes 32
Hybrid interventions 254
Hydrocolloid 70
dressing 72, 73f
Hydrofiber 71
dressing 75, 75f
Hydrogel 42, 70
dressing 72, 72f
Hydroxyethylrutoside 36
Hypercoagulability 267
Hyperlipidemia 87, 93
Hyperplasia, medial 143
Hypertension 87, 93, 143, 151
angiotensin-mediated 144
intractable 127
jumps 147
moderate 147
nonvolume-dependent 144
paroxysmal 147
portal 61
refractory 154
renovascular 141, 144, 146, 166
resistant 147
severe 147, 156, 157
Hypertensive encephalopathy 155
Hysterectomy 62
Iatrogenic pseudoaneurysms 175
Idiopathic aortoarteritis 142
Idiopathic bilateral adrenal hyperplasia 147
Iliac artery 17, 231
Iliac stent implantation 253f
Iliac vein 59f, 61
Iliofemoral deep venous thrombosis 210
Iliofemoral thromboses 273
Immunity, impaired 228
In situ reconstruction 237
Indirect endovascular intervention 284
Indolent situations 128
Infected aneurysm, diagnosis of 232
Infection 93, 101, 223
antecedent 228
contiguous 229
incidence of 139
primary 237
chronic 80
stage of 125
Inflammatory aortic aneurysm 231
Inflow stenosis 116
Infrainguinal autogenous vein graft 4
Infrainguinal revascularization 2t, 3, 9, 12
Infrarenal aortic
aneurysm 126, 238f
occlusion 19
Inguinal ligament 176
Initiate graft lysis 262f
Injury severity score 208
Interposition graft 108, 116
Interventional therapy 129
Intimal fibroplasia 143
Intractable cerebral edema 130
Intractable renovascular hypertension 138f
Intraoperative duplex sonography 164
Intravascular ultrasound 194
Intravenous heparin therapy 273
Intravenous therapy, completion of 235
Ionic contrast agent 150
Irrefutable diagnosis 147
Ischemia 68, 68t, 235, 280
chronic mesenteric 15
duration of 163
end-organ 239
Ischemic cardiac events 10
Ischemic diabetic foot 284
revascularization of 283
Ischemic kidney, ipsilateral 144
Ischemic leg 187f
Ischemic nephropathy 141, 145, 156
pathogenesis of 145fc
pathophysiology of 145fc
Ischemic risk, reduced 10
Ischemic stroke 10
Ischemic ulceration 9
Isolated arterial control 163
Jugular vein, external 115f
segment 102
stenosis 104, 105, 105f
treatment for 105
stenotic lesions 108
disease, chronic 142
disease, end-stage 142
function 153
size, asymmetry in 147
Klebsiella 231
Klippel-Trenaunay syndrome 258f
amputation, left above 187f
extension 96
Lactococcus cremoris 230
Laparoscopy 61
Laser therapy, low-level 79
Left ventricular systolic function 165
and foot, angiosome anatomy of 281f
arteries 281f
heaviness 45
pain 45
wounds, managing 66
Lesions 161
Leukotriene synthesis 39
Ligamentum arteriosum 190
events, high risk for 8
ischemia 101
acute 11
salvage 10, 284
Listeria 230
Lobelenz 90
technique 92f
Local extrinsic causes 57
Low paraplegia rate 200
Low-adherent gauze dressings 42
Lower limb 28, 131
ischemia 9
varicose veins 64
vascularization 279
Low-molecular-weight heparin 9, 272
Lumbar spine procedures 175
Lung 194, 221
Lymphatic drainage 38
Lymphatic dysfunction 32
Lymphovenous malformation 258f
Magnetic resonance
angiography 150
venography 60, 97
anatomy 267
syndrome 55, 56, 57
Mean arterial pressure 102
Mediastinal abnormalities 192
Mediastinal hematomas 192
Mediastinal pleura 201
Melena 16
Mesenteric artery 126
angioplasty and stenting 23
bypass, aortosuperior 19f, 20f
Mesenteric hematoma 21
Mesenteric ischemia
chronic 16t
symptomatic chronic 15
Mesenteric revascularization 17, 24
interventions in 24
Mesenteric vessel occlusions, chronic 17
Mesoglycan 39
Methotrexate 128
Michal technique 91f
Microarterial bypass 91
Microbiology 230
Microcurrent therapy 78
Micronized purified flavonoid fraction 32, 33
Microvascular dysfunction 279
Middle aortic syndrome 130
Milka Greiner's classification 57b
Minilaparotomy 23
Monohydroxyethylrutosides 36
Monotherapy 6
Motor vehicular accident 193f, 197f
Multidetector computed tomography 97, 192
Multiple layer bandages 40
bovis 230
tuberculosis 236f
Mycotic aneurysm 228230
symptomatic 229
Mycotic splenic artery pseudoaneurysm 186f
Myocardial infarction 155
National Kidney Foundation 106
Native vein patch 180
Necrotic tissue 235
Nephrectomy 152
Nephrologist's perspective 153
Neuraxial anesthesia 273, 274t
Neuropathic pain 232
Nickel-titanium alloy 213
Noninflammatory vascular disease 142
Noninvasive tests 58
Nonvenoactive drugs 38
Nuclear medicine 234
Nutcracker syndrome 55, 56
diagnosis of 61
Obesity 93
Obstructive sleep apnea, treatment of 153
Obturator bypass 186
Open operative management 165
Open surgery 107, 116
registry 135t
treatment 17
Optease filter 218, 218f, 219
Oral anticoagulant 2
Oral anticoagulation treatment 40
Oral direct thrombin inhibitors 273
Organ dysfunction 138
Organic erectile dysfunction, etiology of 83t
Original Mobin-Uddin filter 205f
Orodental infections 228
disease 161
endarterectomy 161
lesion 23
Ostioproximal occlusion, bilateral 138f
Ovarian embolization, bilateral 63
Ovarian varicocele, waveform of left 60f
Ovarian vein, left 56, 59, 59f, 63f
Ovarian venous plexus 59
Oxerutins 36
Oxidative stress 101
therapy 81f
wound therapy 81
P2Y12 inhibition 10, 12
Pain 271
Palpable supraclavicular hematoma 192
Paraplegia 196, 199
Patch angioplasty 107, 116
Peak systolic velocity 16
Pelvic arteriovenous malformations 61
Pelvic congestion 54
symptoms 55
syndrome 54, 64
Pelvic pain, chronic 54, 55
Pelvic sonography 58
Pelvic vein 55, 59f
Pelvic venous
disorders 54
insufficiency, chronic 54
reflux 57b, 64
Pelvis 178
venous drainage of 55
erection 89t
hypervascularity 93
numbness 93
shortening 93
tumescence 83
vascular anatomy 84
venous anatomy 86fc
Penile arterial
anatomy 85fc
occlusion 89
Penile revascularization surgery 83, 89b, 93
candidacy for 89
complications with 93t
techniques 90t
Pentoxifylline 38, 39, 46
Percutaneous access 254
Percutaneous graft access 254
Percutaneous transfemoral technique 254
Percutaneous transluminal
angioplasty 20, 106, 108, 112, 115, 118
balloon angioplasty 110
Periaortic fibrosis 126
Perineum 56
Peripheral arterial
disease 1, 1fc, 7fc
interventions, management of 6
Peripheral blood plasma renin activity 148
Peripheral cutting balloon 107
Peripheral vascular
beds 142
disease 146, 249
Peritubular capillaries 153
Periwound skin 67
Permanent filters, types of 207
Perspiration 147
Pharmaco-penile duplex ultrasonography 88, 88t
Phenylephrine 88
Pheochromocytoma 147
Phlebotonic agents 30
Photobiomodulation therapy 79
Pickering syndrome 146
Pinus pinaster 35
Piperacillin 234, 240
Plain balloon angioplasty 23, 105
Plantar flexion 96
Plaque 25
aldosterone concentration 148
renin activity 149
Platelet count 206
Polyester vascular graft 136
Polymeric membrane dressing 71, 76
Polymicrobial biofilm formation 69f
Polypropylene sutures 180
Polytetrafluoroethylene 102, 105, 161
Popliteal adventitial cystic disease 95
Popliteal artery entrapment 95
Popliteal vein 95
access 265f
entrapment 95, 99
Popliteal venous entrapment 95
clinical features 95
diagnosis of 98
etiology 95
management 98
primary 95
surgical treatment 99
Post-endovascular aneurysm repair 249
Post-mechanical thrombectomy 261f
anticoagulation resumption in 274
venous thromboembolism 270t
Pre-existing aneurysms 229
Pregnancy imposes 267
Pregnancy thromboembolism characteristics 267
Pressure alteration 57
Pressure natriuresis 144
Proanthocyanidins 31, 32
Procyanidins 35
Proglide femoral access 250f
Prophylactic indications 208
Prosapogenin 37
Prosthetic bypass graft 132f
Prosthetic graft 186
Proteins, heparin-binding 272
Proteinuria 145
pathogenesis of 145fc
pathophysiology of 145fc
Pseudallescheria boydii 230
Pseudoaneurysm 130, 174, 174f, 175, 177f, 180, 186, 188, 194
access site 176f
groin 181f
infected 186
large 176
majority of 179
repair, surgical options for 181f
traumatic 183
Pseudocoarctation syndrome 192
Pseudomonas 231
Pulmonary edema 155
Pulmonary embolism 95, 206, 209211
Pulmonary vein, left inferior 199
Pulsatile graft 19
Pulseless disease 124
Pycnogenol 35
Radial artery
pseudoaneurysm 175f
puncture 253f
Ray's amputation 79
Reactive oxygen species 145
Reflux pathology 57
Renal arterial stenotic disease, treatment of 155
Renal artery 126
aneurysm, repair of 160f
atheromas 161
bilateral 143
disease 156
dissection 158
left and right 159f
lesions, stenting for 154
reconstructive procedures 158
reimplantation 157, 160
right 138f, 160f
stenosis 141, 141fc, 144, 151
bilateral 144fc
stenting, efficacy of 155
Renal circulations 133
Renal denervation 166
Renal disease, end-stage 101, 280
Renal failure, end-stage 66
Renal function 136, 154
response 166
Renal insufficiency, functional acute 152
Renal parenchymal disease 157
Renal revascularization 152
Renal vascular hypertension, functional test for 148
Renal vein 149
left 55, 59
right 55, 59
Renal vessels 149
Renin-angiotensin-aldosterone system 144
Renography, captopril-enhanced 149
Renovascular disease 141
Renovascular hypertension 152t
etiology for 142, 143t
management of 151fc, 154, 157t
pathogenesis of 144fc
Rest pain 279
severe 187f
Retrograde sheath 254
Retroperitoneal hematoma 176, 178f, 232
Retroperitoneal mass 55
Retroverted uterus 55
Rib 194
spreader 200
Rivaroxaban 5, 7, 10, 11, 12
Rotaflow centrifugal pump 200
Rothia dentocariosa 230
Ruscus aculeatus 44
Salmonella spp 230, 234, 237, 240
Salpingo-oophorectomy 62
Sandwich technique 62, 63f
Santorini plexus 84
Saphenofemoral junction 28
Saphenopopliteal junction 28
Saphenous vein
graft 162
lesser 251
small 251
Saponins 30, 31, 34, 44
Scalp veins, multiple 261f
Scanning electron microscopy 67
Scarpa's fascia 90
Scars, postoperative 91
Scedosporium apiospermum 230
Scintigraphy, captopril-enhanced 149
Sentry bioconvertible filter 224f
Septic emboli 229
Septic thrombosis, acute 284
Serum creatinine 153
Shunts 132
arterioarterial 90
arteriocavernosal 90
arteriovenous 90
Silver 71
dressing 75, 76f
sulfadiazine 40
Skin barrier 40
Sloughy tissues 67
Smoking 16, 93
Sophora japonica 36
Specific surgical techniques 90
Spinal cord 136
perfusion 131
Spinal ischemia 199
Splanchnic-renal bypass 162
Splenorenal bypass 162
SPY machine 79f
Standard pressure balloon 105, 106f
lugdunensis 230
Steno-occlusive disease 126, 129, 133
Stenosis 101, 102f
percentage of 110f
site of 149
Stenotic cephalic vein 108f
Stenotic lesions 20
Stenotic segment and neoanastomosis, excision of 107
choice of 22
placement 116
primary 21
Stent graft 111, 115
challenging 111
repair, endovascular 184f
Sternal fractures 192
Sternum 194
Streptococcus 78
pneumoniae 230
Stroke 66
Subclavian artery 130
pseudoaneurysm 182f
Subclavian bypass, right 135
Subcostal incisions 158
Sulodexide 39
Superior mesenteric artery 15f, 16, 22f
bypass 17, 18f, 19
stenting 23, 24f, 25f
occlusion 136
trunk artery 126
disease 130
Suprarenal abdominal aortic occlusion 138f
Suprarenal filter 212f
principles of 89
role of 156
Surgical management 130
options of 157t
Swing segment stenosis 104
Synthetic products 34
Systemic arterial diseases 283
Tachycardia 147
Takayasu's arteritis 124, 125, 130, 157
Takayasu's disease 124, 126t, 127t, 134, 138, 142
classification of 126, 127t, 129t
signs of 124
symptoms of 124
Taylor's syndrome 54
Tazobactam 234, 240
Teflon felt strips 132
Telangiectasia 28
Tenderness 271
Tetrahydroxyethylrutosides 36
Therapeutic unfractionated heparin 272
Thompson retractors 158
Thoracic aortic aneurysms 183
Thoracic aortic injury 184f
surgery for descending 198
traumatic 190
Thoracic endovascular
aneurysm repair 249
aortic repair 183, 196
graft repair 238
Thoracoabdominal aortic aneurysm 131, 132f134f, 136
Thoracophrenolaparotomy 132
heparin-induced 272, 274
severe 206
Thromboembolic pulmonary hypertension, chronic 210
Thromboembolism 176
Thromboendarterectomy 161
Thrombolysis, catheter-directed 251, 265, 265f
Thrombosis 101
prophylaxis 268, 268t
Thrombotic load, large 25
demonstrate 98
reduction, role of 275
Tibial artery puncture, distal anterior 253f
Tibial vein access, posterior 265f
hypoxia 141
infected 239
Tongue arteriovenous malformation 259f
Topical agents 40
Topical antimicrobials 40
Topical continuous oxygen therapy 80
Topical corticosteroids 40
Tortuosity, severe 197
Tracheobronchial tree 194
Transabdominalduplex 58
Transaortic mesenteric endarterectomy 20
Transaortic thromboendarterectomy 157
Transcatheter aortic valve replacement 249
Transcaval approach 259f
Transcutaneous oxygen pressure 68
Transesophageal echocardiography 194, 234
Transforming growth factors 41
Translumbar permcath 262f
Translumbar stent sac puncture 263f
Transmural incorporation 217
Transvaginal duplex
imaging 60f
ultrasound 58
Traumatic aortic injury, classification of 191f
Treponema pallidum 230
Triamcinolone 40
Trihydroxyethylrutosides 36
Triple-lumen central venous catheter 222
Ulcer 279
healing 41
nonhealing 283
Ultrahigh-pressure balloon 105
Ultra-pressure angioplasty 107
compression 178
thrombin injection 179
Uremia 284
Uterine venous reflux 56
Varicose veins, extensive 29f
Vascular access 101, 249
failing 118fc
Vascular dialysis access, failing 101
Vascular disease 87
Vasopressors 132
Vein 105
abdominal 59f
autologous saphenous 161
axillary 103f
cephalic arch 109
femoral 28
of lower limbs 60
ovarian 55
perforator 28
popliteal 28
quality of 104
right ovarian 59
varicose 28
Vena cava
inferior 55, 59, 205, 206t, 209, 210, 211, 219, 220f, 268f, 275
retrievable inferior 214t
Vena cava filter 219
and litigations, inferior 221
inferior 205
placement of inferior 207
Venoactive drugs 30, 34t, 45, 62
categories of 31t
individual 33
Venography, catheter-directed 61
Venous disease 42
Venous end stenosis, treatment for 115
Venous insufficiency
incidence of 30
medical management of 28
Venous pathology 57
Venous pressure 102
Venous thromboembolism 206, 209, 211, 267
family history for 269
Venous ulcers 46
types of dressings for 43t
Vertebrae 194
Vessel angioplasty, small 92
Virag technique 92, 92f
Viral fever 125
Visceral embolization 282
Viscerorenal occlusive disease 136
Viscerorenal perfusion 131
Viscerorenal steno-occlusive disease 133
Vitamin K antagonist 6
von Hippel-Lindau syndrome 148
Vulva 56
Warfarin 5, 270, 273
Warmth 271
Wound 68, 68t, 69f, 283
assessment 66
chronic 66
debridement 67
healing 283, 284
management 66
Xiphopubic incision 158
Yersinia 231
Zinc bandages 40
Chapter Notes

Save Clear

Current Evidence for Anticoagulation Following Infrainguinal RevascularizationCHAPTER 1

Pinjala Ramakrishna
Peripheral artery disease (PAD) is a major lower limb vascular problem. Lower extremity PAD affects about 200 million people worldwide.1 Acute and limb-threatening thrombotic complications are more common in PAD patients. There is high risk of coronary heart disease (CHD) and diseases of other vascular beds in the patients with PAD patients. Surgical bypass, percutaneous angioplasty, and medical therapies play an important role in the management of PAD at different stages of the atherosclerosis. Statins, antiplatelets, and anticoagulants are used in the PAD patients before and after interventions or surgery (Flowchart 1). There is enough evidence to support the use of antiplatelet agents in symptomatic PAD patients to reduce the major adverse cardiovascular events (MACEs) with and without interventional treatments. Anticoagulation therapy is used in selected high-risk group of patients in the perioperative period to reduce the risk of thrombotic complications. Anticoagulation is also used in patients with severe procedural difficulties which can affect the patency rates of the revascularization. The selection of the anticoagulants is based on their mechanism action, availability of class of anticoagulants (Table 1). There is less significant evidence in favor of some anticoagulants to confirm their efficacy in improving the results of revascularization. These anticoagulants are low-molecular-weight dextran-40, glycoprotein (IIb/IIIa) receptor antagonists, direct thrombin inhibitors, and factor Xa inhibitors. Antiplatelets and anticoagulants (aspirin + warfarin) are used in combination in the selected group of postoperative patients to improve the patency rates of vascular segments treated with angioplasty or bypass.
zoom view
Flowchart 1: Antithrombotic treatment in peripheral arterial disease.
Table 1   Anticoagulants and infrainguinal revascularization.
Anticoagulants used in infrainguinal revascularization
  1. Inj. Heparin (UFH)
  2. Inj. LMWH (different types)
  3. Tab Warfarin/Acitrom
  4. Tab. DOACs (Direct Iia/Xa inhibitors)
  5. Aspirin + Warfarin
  6. Clopidogrel + Warfarin
  7. Aspirin + DOACs
  8. LOMODEX-40
  9. Dipyridamole
  10. GP IIb/IIIa inhibitors
But the major concern is about the increased incidence of fatal or nonfatal bleeding in those patients on combination therapies. The bleeding factor discourages us to use this combination and search for adequate evidence for the appropriate use of anticoagulants in the different types of PAD patients. The specific need for anticoagulants in PAD patients after infrainguinal revascularization procedures should be established from the evidences available to us. Today, aspirin still stands out as the effective basic medical therapy after angioplasty or bypass in the lower limb. Dual antiplatelet therapy (aspirin + clopidogrel) is prescribed for limited period and then single antiplatelet therapy for longer period of time in many vascular surgical clinics across world. In addition, combinations such as dipyridamole + aspirin and cilostazol + aspirin have also been used in some centers with some evidence. Different trials have shown that oral anticoagulant (OAC) warfarin is beneficial in PAD patients when a vein graft used for lower limb revascularization. In the immediate periprocedural period, injection heparin retains its significant importance in the prevention of early thrombotic complications after revascularization. Now, new evidence is emerging with a trend toward the use of dual channel inhibition with aspirin and low-dose direct OAC from recent trials.
Antithrombotic Trialists’ Collaboration (ATC) in 2002, conducted meta-analysis of randomized controlled and reported the efficacy of antiplatelet agents in patients at high risk for vascular occlusive disease events. This meta-analysis included 42 trials comprising 9,214 patients with symptomatic PAD. It showed 23% reduction in serious vascular events with antiplatelet therapies. The Antiplatelet Trialists’ Collaboration also reported a relative risk reduction of 43% (p < 0.001) in peripheral vascular graft occlusion with antiplatelet therapies.2 The risk of MACE was reduced by 22% with antiplatelet therapy in a subgroup of 2,497 patients undergoing peripheral vascular grafting. Cochrane review showed better 1-year infrainguinal bypass graft patency after taking aspirin with or without dipyridamole.3 The beneficial effect of aspirin was more in patients with prosthetic grafts. Aspirin is recommended (grade 1) based on the available Level-1 evidence. Clopidogrel is recommended as secondary agent in the treatment of patients after recanalization or bypass.3
Table 2   Expectations from anticoagulation.
Expectations from anticoagulation in patients after infrainguinal revascularization
Prevention of
  1. Early thrombosis
  2. Limb ischemia
  3. Amputation
  4. Restenosis
  5. Major adverse cardiovascular event (MACE)
  6. MI
  7. Stroke
  8. CV death
  9. Need for target vessel revascularization
The effect of aspirin was compared with aspirin and clopidogrel in patients undergoing below the knee bypass grafting in CASPAR trial. No difference was noted in the composite rate of graft occlusion, revascularization, amputation or death between the two groups. Patients with prosthetic grafts were benefited with dual antiplatelet therapy (clopidogrel and aspirin) than monotherapy (aspirin) alone. Any type of bleeding was more common with dual antiplatelet therapy, but the incidence of severe bleeding was similar in both the groups.4 Despite meticulous surgical techniques and skillful surgeons, there is still failure of infrainguinal bypass grafts and it is yet to be answered satisfactorily. This is a matter of concern for both the patients and surgeons treating them. If patients are not given postoperatively antithrombotic agents, 28–45% of all bypass grafts will occlude in the first year after operation and most of them occur in the early postoperative period. PAD patients are not only threatened by major adverse limb events (MALEs) but also by the cardiovascular and cerebrovascular complications of atherosclerotic origin. The MACE events were more common in the PAD patients than in the normal subjects. We expect that anticoagulation will prevent majority these complications after infrainguinal revascularization (Table 2).
The efficacy of conventional OACs was compared with antiplatelet drugs in preventing ischemic complications after infrainguinal bypass surgery in Dutch Bypass Oral Anticoagulants or Aspirin study.5 Patients (2,690) were randomized to receive aspirin 80 mg daily or oral anticoagulation with a target international normalized ratio (INR) range of 3.0–4.5. This study was an unblinded study. Surgeons were permitted to use adjunctive treatment when they felt it was needed. The patients on treatment were followed for 21 months. Graft occlusion was taken as the primary outcome. The secondary outcomes were vascular death, stroke, myocardial infarction (MI), and limb amputation. There was no difference or superiority in the effectiveness between the two groups. It was observed that oral anticoagulation was superior to aspirin in preventing the occlusion of autologous vein grafts. Aspirin was found to be better in synthetic grafts. Secondary outcome events were few 4with oral anticoagulation but it was not statistically significant. The annual incidence of major bleeding was 4.7% in the group taking anticoagulation. The annual incidence of major bleeding was only 2.5% in the group taking aspirin tablets. Fatal bleeds were more in anticoagulation group (16 patients) and less in aspirin (12 patients) group. It was concluded that the vein graft occlusion was less with anticoagulation group but at the same time it was also found that the incidence of bleeding was more in those who received anticoagulation.
Tangelder et al. (1999) conducted a systematic review of randomized trials. They found that antiplatelets and anticoagulants are helpful in preventing lower limb bypass graft-related complications, but it was based on small number of trials.6 It was concluded that antiplatelet therapy and OAC therapy reduce the risk of graft occlusion. OAC therapy appears to be the more effective in the treatment in high-risk patients. But the effect on the reduction of risk of stroke, MI, and death was inconclusive. The collected evidence for the beneficial effects of antiplatelet and OAC therapies after infrainguinal bypass surgery is based on a small number of trials only. There is no proof to say which modality is the most effective and superior to the other in the prevention of graft occlusion and ischemic events in the patients after infrainguinal bypass surgery, which is the reason to conduct a large, randomized comparison trial of aspirin with OACs. Sarac et al. (1998) observed that perioperative anticoagulation with injection heparin increased the incidence of wound hematomas.7 Long-term anticoagulation with warfarin improved the limb salvage rate for patients at high risk of for graft failure. Infrainguinal autogenous vein graft bypass patency also improved with long-term warfarin therapy. This has prompted surgeons to consider postoperative anticoagulation in select group of patients who are at high risk of graft failure. If the long-term oral anticoagulation is helpful after bypass surgery, then how long one can safely continue the anticoagulation in them? Long-term anticoagulation is associated with risk of different types of bleeding (Table 3). A clinical trial was conducted in one single center and continued anticoagulation during 10 years to determine long-term OAC treatment effect on improving graft performance and prevention of major amputation following vein bypass surgery for femoropopliteal atherosclerosis.
Table 3   Bleeding complications of anticoagulation.
Different types of bleeds
  • Fatal bleeds
  • Major bleeds
  • Minor bleeds
  • Clinically relevant nonmajor bleeds
  • Wound hematomas
  • Drug interactions and bleeds5
Patients (130) electively received a femoropopliteal vein graft, they were randomly assigned to a therapy group [treatment with phenprocoumon (n = 66 patients)] and a control group (n = 64 patients) without any anticoagulant treatment. Primary endpoints of the study were graft occlusion and limb loss. The median durations of primary patency and limb salvage were significantly longer for treated patients than that for controls. Survival in the therapy group was longer. The authors, Kretschmer et al., concluded that following autologous vein bypass surgery, the results were superior in terms of graft patency, limb salvage, and survival in the group treated with anticoagulant.8
The goal in the management of PAD patients is to reduce the MALE and MACE. Intensified antithrombotic therapy is recommended to achieve this dual benefit. This led to the search for better drug combination therapies such as an antiplatelet and anticoagulant. Warfarin and antiplatelet vascular evaluation (WAVE) trial is the one of them. This trial compared the antiplatelet alone with antiplatelet (aspirin, ticlopidine or clopidogrel) and anticoagulant warfarin (INR 2.0–3.0). Dual antiplatelet therapy was not permitted in this study except in those who suffered an MI or underwent coronary stenting during follow-up. In CHARSIMA trial, dual antiplatelet therapy did not show different limb outcomes from the single antiplatelet therapies.9 It has been the basis for avoiding the dual antiplatelet therapy in the subsequent trials. In the WAVE trial, there was no significant difference in the primary outcomes (MI, stroke, lower extremity ischemia) between the both groups. The results of the WAVE trial discouraged the use of this combination of antiplatelet and anticoagulant warfarin therapy. On one side there was no benefit in the MACE, MALE and on the other side there was increase in the life-threatening bleeding (4.0% vs. 1.2%). The recent emergence of novel OACs (NOACs) has rekindled the interest of using them along with aspirin to reduce the MALE and MACE.10
Cardiovascular outcomes for people using anticoagulation strategies (COMPASS) study was conducted to test the benefit of combining the NOAC plus aspirin in preventing the MALE and MACE. It showed that rivaroxaban in combination with aspirin was more effective than aspirin alone in preventing the recurrent cardiovascular events with safety in patients with stable cardiovascular atherosclerotic vascular disease.11 In this trial, patients who were assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin or rivaroxaban 5 mg twice daily. In addition, patients who received rivaroxaban 5 mg twice daily had more major bleeding events. Prevention of a MALE is of paramount importance among individuals with lower limb PAD. The prognosis after an episode of MALE is poor. After an episode of MALE, there is a threefold increase in death and 200-fold increase in the risk of subsequent vascular amputation. MALE is more common in a subset of population such as those with history of peripheral vascular revascularization, amputation, severely symptomatic leg ischemia at baseline or those on treatment with single antiplatelet drug therapy. So, Anand et al. (2018) reported that prevention of MALE is of utmost importance as this is associated with a poor prognosis.126
Endovascular interventions are more commonly performed than bypass surgery as a treatment of lower extremity PAD. More endovascular interventions were performed for every one procedure declined in lower extremity bypass surgery. In addition to lower extremity vascular bypass procedures, endovascular procedures are also improving rates of limb salvage in patients with PAD. There is a role for the antiplatelets and anticoagulants in patients undergoing infrainguinal endovascular therapies to additionally improve the early and late outcomes. Aspirin alone significantly reduced the MACE (2.5% vs. 3.6%) when compared with the placebo. ATC reported this point based on the meta-analysis of the antiplatelet therapy trials in patients of peripheral angioplasty.2 In a Cochrane meta-analysis of three studies, high-dose aspirin and dipyridamole showed superior patency after revascularization at the end of 6 months.13
The MIRROR (Management of peripheral arterial interventions with mono or dual antiplatelet therapy) trial was done to evaluate the effect of dual antiplatelet therapy after angioplasty. This study randomized patients (80) undergoing peripheral angioplasty with or without stenting to dual antiplatelet therapy (clopidogrel plus aspirin) and monotherapy (aspirin) for 6 months.14 The rate of target lesion revascularization (TLR) is defined as need for repeat revascularization of a lesion that was initially treated with angioplasty or stenting. The rate of TLR was lower in the dual antiplatelet therapy (clopidogrel plus aspirin) group than in the monotherapy (aspirin) group at 6 months (5% vs. 8%; p = 0.04). But this benefit of TLR was lost during the follow-up at end of 1-year (25% vs. 32%; p = 0.35). Cilostazol is a phosphodiesterase type 3 inhibitor. It has antiplatelet properties. Its antiplatelet effects are studied in small, controlled trials. PAD patients undergoing endovascular revascularization were given cilostazol to study the beneficial effects. However, data obtained in these trials is not convincing and it is inadequate to confirm its efficacy.
Patients who are undergoing revascularization for PAD should be considered for lifelong antithrombotic therapy. Dual antiplatelet therapy (aspirin + clopidogrel) and dual pathway inhibition (rivaroxaban + aspirin) are reasonable strategies to benefit the symptomatic PAD patients irrespective of the type of revascularization. Intensification of antithrombotic therapy in another strategy when the patients are at high risk for MALEs such as acute ischemic thrombosis or amputation. There are several factors that increase the limb risk (MALE). They are synthetic graft infrainguinal bypass, infrapopliteal bypass, poor quality of the conduit, inadequate arterial runoff, diffuse lesions, gangrene, or tissue loss (Table 4). In such situations, antiplatelet therapy can be intensified to dual pathway inhibition (aspirin + rivaroxaban), dual antiplatelet therapy (aspirin + clopidogrel), or conventional oral anticoagulation with a vitamin K antagonist. The current data is strongly supports the use of dual pathway inhibition (aspirin + rivaroxaban) with respect to lowering MALE events in symptomatic PAD patients.7
Table 4   Factors with increased limb risk requiring intensification of antithrombotic treatment.
Factors with increased risk to limb
  • Prosthetic infrainguinal bypass
  • Below the knee bypass
  • Suboptimal conduit
  • Poor arterial runoff
  • Extensive ischemic lesions
  • Tissue loss
zoom view
Flowchart 2: Clinical decision making for antithrombotic therapies in peripheral arterial disease patients.
We should assess the risk of limb amputation and ischemic risks. These must be weighed against bleeding risk. It is important to note that triple therapy with two antiplatelet agents plus anticoagulation may be attractive and appear to be effective. But it should be avoided because the triple therapy is associated with high major bleeding rates.7,15,16
The standard of care is to treat patients undergoing endovascular revascularization (angioplasty with or without stenting), with dual antiplatelet therapy for 1–6 months. But there is no strong evidence to support this practice (Flowchart 2). This strategy is based on the data obtained from the MIRROR study. The next question is do we need to consider tailored antithrombotic therapies in patients undergoing different types of revascularization methods? The evidence is inadequate to recommend tailored antithrombotic regimens in patients undergoing conventional balloon angioplasty versus drug-eluting balloon angioplasty or bare-metal versus drug-eluting stenting.14,17 The initial treatment should be followed by lifelong single antiplatelet therapy (aspirin or clopidogrel). The recent data suggests that the dual pathway inhibition (rivaroxaban + aspirin) is beneficial in chronic stable disease patients. This evidence is based on the data from COMPASS trial. The VOYAGER PAD 8[Vascular Outcomes study of ASA (acetylsalicylic acid) along with rivaroxaban in Endovascular or surgical limb Revascularization for PAD] trial provided information regarding the most effective antithrombotic regimen in patients who have undergone surgical or endovascular revascularization for PAD.18 In patients who are at persistently at high risk for limb events, prolonged dual antiplatelet therapy or dual pathway inhibition should be considered. However, the benefit of prolonged dual antiplatelet therapy and dual pathway inhibition should always be weighed against the higher risk for bleeding.19
A multicenter, prospective, nonmasked clinical trial was conducted in patients (831) who underwent peripheral arterial bypass surgery were compared in a long-term treatment with warfarin + ASA (with a target INR of 1.4–2.8) with ASA alone. The primary endpoint was vascular bypass patency. The mortality and morbidity were the secondary endpoints. In the warfarin + ASA (WASA) group, there were 133 deaths (31.8%) and 95 deaths in the ASA group. Major hemorrhagic events occurred frequently in the WASA group (WASA, n = 35; ASA, n = 15; p = 0.02). The patency rate in 8-mm prosthetic bypass subgroup was not significantly different. But patency rate in the 6-mm bypass subgroup was significantly different (femoral-popliteal; 71.4% in the WASA group vs. 57.9% in the ASA group; p = 0.02). The patency rate was unaffected in the vein bypass group (75.3% in the WASA group vs. 74.9% in the ASA group). Therefore, administration of warfarin in combination with aspirin has only a few selected indications for improvement of bypass graft patency and it is associated with an increased risk of morbidity and mortality. In summary, aspirin administration still remains the mainstay of antithrombotic therapy to prevent bypass thrombosis (MALE) and other cardiovascular events (MACE) in patients undergoing lower extremity arterial bypass, for long period of time. Low-dose warfarin therapy may provide some additional patency benefit for patients with a femoropopliteal prosthetic bypass graft (6 mm) and for patients with a vein bypass that is at high risk for thrombosis. The addition of warfarin therapy significantly increases the risk of hemorrhagic events also.20
In another randomized, prospective study, Monaco et al. compared the effect of OAC therapy plus clopidogrel (C), was compared with dual antiplatelet therapy on peripheral vascular and systemic cardiovascular outcomes in patients after femoropopliteal bypass surgery. They have randomized 349 patients who had undergone femoropopliteal bypass surgery. In one group of 173 patients received clopidogrel 75 mg/day plus warfarin (C + OAC), and in the other group of 168 patients received dual antiplatelet therapy with clopidogrel 75 mg/day plus aspirin 100 mg/day. The graft patency, occurrence of severe ischemia, and the incidence of bleeding episodes were the study endpoints. The patients were followed for 4–9 years. The graft patency rate and the freedom from severe arterial ischemia was significantly higher in C + warfarin group than in C + ASA group. The linearized incidence of minor bleeding complications in C + OAC group was significantly higher than in C + ASA group (2.85% patient-years vs. 1.37% patient-years). The incidence of MACEs, including mortality, was similar for both study groups. It was 9concluded that in patients who undergo femoropopliteal vascular bypass surgery, combination therapy with clopidogrel plus warfarin is more effective than dual antiplatelet therapy in increasing graft patency and reducing severe peripheral ischemia. These two benefits are obtained at the cost of an increased risk of minor anticoagulation-related bleeding.20
The use of injection of low-molecular-weight heparin (LMWH) was also proposed instead of OAC therapy to improve the results of vascular bypass grafts. A study was done to assess the benefits of long-term postoperative dalteparin treatment to improve the primary patency of peripheral arterial bypass grafts (PABGs) in lower limb ischemia patients who were taking ASA treatment. This was a prospective randomized double-blind multicenter study. Patients (284) with lower limb ischemia (ischemic ulceration or partial gangrene) from 12 hospitals were randomized, after arterial bypass grafting to receive injection dalteparin 5,000 IU or placebo injection once daily for 3 months. All these patients also received 75 mg of ASA daily for 12 months. The graft patency was assessed at 1, 3 and 12 months. At end of 1 year, 42 patients had died or were lost to follow-up. The compliance with the injection schedule was good (80%). Primary patency rate, in the dalteparin was 83% at 3 months and in the control group it was 80%. Primary patency was only 59% for both the groups at end of 12 months. Major complication rates and cardiovascular morbidity were similar in the two groups. In patients who are taking ASA treatment addition of long-term postoperative dalteparin treatment did not improve patency after peripheral artery bypass grafting. Therefore, addition of LMWH treatment cannot be recommended to improve the results for routine use in vascular patients after leg bypass surgery for critical lower limb ischemia.21
There is evidence to suggest that drugs which reduce platelet aggregation, such as higher-dose aspirin, can also reduce the rate of reocclusion 6 months after surgery. But evidence for longer-term restenosis rates and on associated side effects are scarce. Similarly, there is some evidence of variation in the reocclusion/restenosis rates according to different antiplatelet drugs. The rate of reocclusion/restenosis is lower in people taking cilostazol compared with ticlopidine at 12 months after surgery. In patients with more severe disease, if they take LMWH in addition to aspirin compared with aspirin alone, the results were better. Betrixaban plus aspirin compared with aspirin alone may also be an effective treatment in diabetic patients. The available supporting trials are generally small and of variable quality. The side effects of drugs are 10not consistently observed. We still need good quality, large-scale randomized controlled trials, grouped by severity of disease.
Few studies showed that there is no benefit at all with the addition of coumarin treatment in femoropopliteal and femorodistal reconstructive surgery. Arfvidsson et al. (1990) studied the effect of coumarin on patency, limb salvage, and survival after primary femoropopliteal and femorodistal reconstructions. In this study, 116 patients were randomized into 61 in the study group and 55 in the control group. All patients were treated postoperatively with heparin. Patients in the study group received dicoumarol orally postoperatively.22 The overall patency after 1 year was 75±6%, compared with 74 ± 6% in the study and control groups. The patency after 2 years was 65 ± 9 compared with 57 ± 8% in the study and control groups. The patency after 3 years was 46 ± 11% compared with 42 ± 9% in the study and control groups, respectively. There were no statistically significant differences in limb salvage or survival rates between the two groups. Anticoagulation with coumarin treatment was associated with serious bleeding complications in 4–5% of the study patients. The limb salvage was lower in patients treated for critical ischemia (p < 0.03), and this was also true for survival (p < 0.04). This was also influenced by the level of the reconstruction. The survival was lower in patients undergoing femorodistal reconstructions (p < 0.001). The results of the study demonstrated that long-term coumarin treatment failed to improve outcome in routine femoropopliteal and femorodistal reconstructive surgery.
Revascularization of the ischemic lower limbs increases the risk of ischemic cardiac events (MACE) and limb (MALE) events in patients with PAD. Although intensification of antithrombotic therapy after revascularization has demonstrated benefit in patients with coronary artery disease populations. This approach has not been well studied or it has not shown consistent benefit in PAD. But the new evidence is emerging from the recent studies. The COMPASS trial demonstrated that a treatment strategy of dual pathway inhibition (rivaroxaban + aspirin) reduced ischemic risk (MACE) in patients following recent acute coronary syndromes, as well as in patients with stable atherosclerotic vascular disease. We are searching for similar evidence to confirm that these benefits are extended to the symptomatic lower-extremity PAD patients undergoing revascularization. This became the objective of the VOYAGER PAD trial.18
VOYAGER PAD is a randomized, double-blind, placebo-controlled international trial. This study evaluated the efficacy and safety of rivaroxaban in symptomatic PAD patients undergoing a peripheral revascularization through surgical and/or endovascular procedures. Patients are randomized to either rivaroxaban 2.5 mg twice daily or placebo. Both groups received low-dose aspirin (100 mg daily). In addition, surgeons were allowed to use a limited course of P2Y12 inhibition (clopidogrel) as an adjunctive measure. The primary efficacy endpoint is composite of MI, ischemic stroke, cardiovascular death, acute limb ischemia, and major amputation of vascular etiology. The primary safety endpoint is major bleeding in accordance with the thrombolysis 11in MI (TIMI) definition. Secondary safety outcome was major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH). This trial randomized 6,564 patients, 3,286 were assigned to rivaroxaban and 3,278 were assigned to placebo. Primary efficacy outcome was achieved in 508 patients in the rivaroxaban group and in 584 patients in the placebo group. TIMI major bleeding occurred in 62 patients in the rivaroxaban group and in 44 patients in the placebo group. The secondary safety outcome ISTH major bleeding occurred in 140 patients from rivaroxaban group and 100 patients from placebo group.
VOYAGER PAD study provides evidence to say that rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, MI, ischemic stroke, or death from cardiovascular causes than aspirin alone in patients who had undergone lower limb revascularization. There was no significant difference in the incidence of TIMI major bleeding between the groups. The incidence of ISTH major bleeding was significantly higher with rivaroxaban and aspirin than with aspirin alone.
Lastly, it is important to understand the factors that affect autogenous vein graft failure after bypass surgery. If we understand and address these factors, we can limit the dependence on strategies of antiplatelet and anticoagulant therapies to improve the patency of revascularized segments. Schanzer et al. conducted a prospective trial to identify technical variables affecting the early and midterm outcomes of autogenous vein bypass for limb salvage.15 The PREVENT III trial included 1,404 patients after lower extremity bypass using autogenous vein graft bypass for critical limb ischemia (CLI). The patients with claudication and patients who had in situ reconstructions were excluded from the study protocol. The effect of the technical factors such as diameter of vein, type of conduit, length of graft, orientation of vein, proximal and distal anastomosis location and completion imaging was analyzed at 30 days and 1 year. The effect of these technical factors on 30-day and 1-year outcomes of grafts was analyzed by univariate analysis. The primary patency, primary-assisted patency (PAP), and secondary patency were assessed by Kaplan–Meier method. In 30 days, vein grafts with a diameter < 3.5 mm and composite grafts showed early graft failure (Table 5). At 1 year, patency rates were poor with vein graft diameter < 3.5 mm, nongreat saphenous vein (non-GSV) type and vein grafts longer than 50 cm. However, limb salvage and survival at 1 year were not significantly affected by technical variables. The study of high-risk conduits (diameter < 3 mm or nonsingle segment GSV) revealed their use was associated with a 2.1-fold increased risk of 30-day graft failure. At the same time, primary patency, PAP, and secondary patency at 1 year were also reduced. The patients who received high-risk conduit showed a prolonged hospital stay (mean 9.37 vs. 8.71 days, p = 0.03) and increased number of reinterventions (mean 0.67 vs. 0.42, p < 0.0001) in a year. This large, multicenter study of patients undergoing lower extremity bypass for CLI concluded that vein diameter and type of conduit were important and main determinants of early and late bypass graft failure.1512
Table 5   Conduit-related factors affecting the patency of graft.
Factors affecting the patency rates after revascularization in 30 days and at 1 year (Primary patency/Primary assisted patency/secondary patency)
  • Vein graft diameter <3.5 mm
  • Non-GSV graft
  • Graft length >50cm
  • Non single GSV
Therefore, high-risk conduits and longer grafts will be benefited by aggressive postoperative graft surveillance. In addition to graft surveillance, effective and safer medical therapies with antiplatelet drugs and anticoagulant agents will also improve the outcomes.
In conclusion, antiplatelet agents and anticoagulants have an important role to play in the perioperative management of infrainguinal bypass and revascularization. A study of 85,830 patients undergoing peripheral vascular intervention in the United States of America revealed that 18.3% were treated with an OAC after procedure. In those who received anticoagulation 19.1% did not receive P2Y12 inhibitor, 30.8% received a P2Y12 inhibitor before and after the procedure. Duration of P2Y12 inhibitor therapy was also variable. Only 6.2% of patients were treated with a P2Y12 inhibitor for <30 days and 25.6% received P2Y12 inhibitor for >30 days.23 Anticoagulation can benefit with reduction of MACE and MALE more than the risk of bleeding after infrainguinal revascularization in appropriately selected patients. Now the newly introduced combination therapy, rivaroxaban plus aspirin seems to be promising in reducing the MACE and MALE during the long-term follow-up. The future research will continue to find better, safer anticoagulation agents which can give not only controlled, effective anticoagulation but also limit the risk of bleeding after infrainguinal revascularization.
  1. Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013;382:1329–40.
  1. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high-risk patients. BMJ. 2002;324:71–86.
  1. Bedenis R, Lethaby A, Maxwell H, Acosta S, Prins MH. Antiplatelet agents for preventing thrombosis after peripheral arterial bypass surgery. Cochrane Database Syst Rev. 2015;(2):CD000535.
  1. Belch JJ, Dormandy J; CASPAR Writing Committee, Biasi GM, Cairols M, Diehm C, et al. Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial. J Vasc Surg. 2010;52(4):825–33.e1-2.

  1. 13 Dutch Bypass Oral anticoagulants or Aspirin (BOA) Study Group. Efficacy of oral anticoagulants compared with aspirin after infrainguinal bypass surgery (The Dutch Bypass Oral Anticoagulants or Aspirin Study): a randomized trial. Lancet. 2000:355(9201):346–51.
  1. Tangelder MJ, Lawson JA, Algra A, Eikelboom BC. Systematic review of randomized controlled trials of aspirin and oral anticoagulants in the prevention of graft occlusion and ischemic events after infra inguinal bypass surgery. J Vasc Surg. 1999;30:701–9.
  1. Sarac TP, Huber TS, Back MR, Ozaki CK, Carlton LM, Flynn TC, et al. Warfarin improves the outcome of infrainguinal vein bypass grafting at high risk for failure. J Vasc Surg. 1998;28(3):446–57.
  1. Kretschmer G, Herbst F, Prager M, Sautner T, Wenzl E, Berlakovich GA, et al. A decade of oral anticoagulant treatment to maintain autologous vein grafts for femoropopliteal atherosclerosis. Arch Surg. 1992;127(9):1112–5.
  1. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354:1706–17.
  1. WAVE Investigators. The effects of oral anticoagulants in patients with peripheral arterial disease: rationale, design, and baseline characteristics of the warfarin and antiplatelet vascular evaluation (WAVE) trial, including a meta-analysis of trials. Am Heart J. 2006;151:1–9.
  1. Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR, Hart RG, Shestakovska O, et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017;377:1319–30.
  1. Anand SS, Caron F, Eikelboom JW, Bosch J, Dyal L, Aboyans V, et al. Major adverse limb events and mortality in patients with peripheral artery disease. The COMPASS trial. J Am Coll Cardiol. 2018;71:2306–15.
  1. Robertson L, Ghouri MA, Kovacs F. Antiplatelet and anticoagulant drugs for prevention of restenosis/reocclusion following peripheral endovascular treatment. Cochrane Database Syst Rev. 2012;(8):CD002071.
  1. Tepe G, Bantleon R, Brechtel K, Schmehl J, Zeller T, Claussen CD, et al. Management of peripheral arterial interventions with mono or dual antiplatelet therapy—the MIRROR study: a randomised and double-blinded clinical trial. Eur Radiol. 2012;22(9):1998–2006.
  1. Schanzer A, Hevelone N, Owens CD, Belkin M, Bandyk DF, Clowes AW, et al. Technical factors affecting autogenous vein graft failure: observations from a large multicenter trial. J Vasc Surg. 2007;46:1180–90.
  1. Taylor SM, Kalbaugh CA, Gray BH, Mackrell PJ, Langan EM 3rd, Cull DL, et al. The LEGS score: a proposed grading system to direct treatment of chronic lower extremity ischemia. Ann Surg. 2003;237:812–9.
  1. Strobl FF, Brechtel K, Schmehl J, Zeller T, Reiser MF, Claussen CD, et al. Twelve-month results of a randomized trial comparing mono with dual antiplatelet therapy in endovascularly treated patients with peripheral artery disease. J Endovasc Ther. 2013;20:699–706.
  1. Capell WH, Bonaca MP, Nehler MR, Chen E, Kittelson JM, Anand SS, et al. Rationale and design for the vascular outcomes study of ASA along with rivaroxaban in endovascular or surgical limb revascularization for peripheral artery disease (VOYAGER PAD). Am Heart J. 2018;199:83–91.

  1. 14 Johnson WC, Williford WO, Department of Veterans Affairs Cooperative Study. Benefits, morbidity, and mortality associated with long-term administration of oral anticoagulant therapy to patients with peripheral arterial bypass procedures: a prospective randomized study. J Vasc Surg. 2002;35:413–21.
  1. Monaco M, Di Tommaso L, Pinna GB, Lillo S, Schiavone V, Stassano P. Combination therapy with warfarin plus clopidogrel improves outcomes in femoro-popliteal bypass surgery patients. J Vasc Surg. 2012;56(1):96–105.
  1. Jivegard L, Drott C, Gelin J, Groth O, Hensäter M, Jensen N, et al. Effects of three months of low molecular weight heparin (dalteparin) treatment after bypass surgery for lower limb ischemia—a randomised placebo-controlled double-blind multicentre trial. Eur J Vasc Endovasc Surg. 2005;29(2):190–8.
  1. Arfvidsson B, Lundgren F, Drott C, Scherstén T, Lundholm K. Influence of coumarin treatment on patency and limb salvage after peripheral arterial reconstructive surgery. Am J Surg. 1990;159(6):556–60.
  1. Jones WS, Mi X, Qualls LG, Turley RS, Vemulapalli S, Peterson ED, et al. Significant variation in P2Y12 inhibitor use after peripheral vascular intervention in Medicare beneficiaries. Am Heart J. 2016;179:10–8.