VASCULAR SURGERY e II
Acute and chronic lower limb
ischaemia
George Peach
Ian M Loftus
Abstract
Limb ischaemia is a common clinical condition that causes considerable
morbidity and mortality and represents a major drain on healthcare re-
sources. Peripheral arterial disease (PAD) is the leading cause of both
acute and chronic limb ischaemia. Chronic limb ischaemia may also be
caused by non-atherosclerotic processes such as arterial entrapment,
fibrosis or arteritis. Acute limb ischaemia may be also due to embolism,
thrombosis or trauma. Duplex ultrasonography, computed tomography
angiography and magnetic resonance angiography are now conventional
forms of arterial imaging, with catheter angiography reserved for interven-
tion. Risk factor modification is extremely important for all these patients,
since many will also have significant coronary or cerebrovascular disease.
Those with claudication often improve with structured exercise and if
symptoms progress they may benefit from angioplasty or stenting. Arte-
rial bypass remains the mainstay of treatment for patients with critical
limb ischaemia if they are fit enough for surgery. Acute limb ischaemia
is a surgical emergency and can be treated with surgical embolectomy
or catheter-directed thrombolysis (depending on local expertise). Patients
with irreversible limb ischaemia should be treated with primary amputa-
tion or palliation as appropriate.
Keywords Acute leg ischaemia; angioplasty; arterial bypass; limb
ischaemia; peripheral artery disease
Chronic limb ischaemia
The most common cause of chronic lower limb ischaemia is
atherosclerotic peripheral arterial disease (PAD). PAD has an
estimated worldwide prevalence of nearly 10%, rising to as
much as 15e20% in those over 70 years of age and affects some
27 million people in Europe and North America alone.1 Critical
limb ischaemia (CLI) e the most severe manifestation of PAD e
may lead to limb loss or even death unless treated promptly.
Each year, 500e1000 new cases of CLI are diagnosed per million
of the population, with an estimated annual cost to the NHS of
more than £200 million.2
Risk factors
The development of atherosclerotic PAD is a multifactorial pro-
cess involving both modifiable and non-modifiable risk factors.
George Peach MBChB MRCS is a Clinical Research Fellow at St George’s
Vascular Institute, London, UK. Conflicts of interest: none declared.
Ian M Loftus MBChB MD FRCS is Consultant Vascular Surgeon and Reader
in Vascular Science at St George’s Vascular Institute, London, UK.
Conflicts of interest: none declared.
SURGERY 31:5
Non-modifiable risk factors include:
 age
 gender
 ethnicity.
Modifiable risk factors include:
 smoking
 diabetes mellitus/poor glycaemic control
 hypertension
 hyperlipidaemia
 hypercoagulability.
Other factors
Up to 30% of young patients with PAD have high homocysteine
levels (compared to 1% in the general population) and there is
now evidence that this is an independent risk factor for PAD.3
Raised haematocrit, high plasma fibrinogen levels and chronic
renal insufficiency also seem to be linked to an increased risk of
PAD though evidence for these links being causal remains
limited. Patients with both end-stage renal disease and diabetes
are at extremely high risk of limb loss.4
Intermittent claudication (IC)
Though many never develop symptoms, up to 15% of patients
with asymptomatic PAD will develop IC within 5 years.5 Of those
who do develop IC, only 20e25% are likely to experience further
clinical deterioration.6 Major amputation is rare (other than in
those with diabetes) and patients should be reassured accord-
ingly. Only 1e3% of patients with IC will require major ampu-
tation within a 5-year period.6
Clinical features: intermittent claudication is an aching muscle
pain, brought on by exercise, and rapidly relieved by rest. Pain
arises due to increased oxygen demand of the tissues during
exercise. Symptoms are determined by site of disease and since
PAD most commonly affects the superficial femoral artery (SFA),
pain is usually felt in the calf (i.e. distal to the arterial stenosis/
occlusion). Disease of aorto-iliac, common femoral or tibioper-
oneal vessels may give rise to pain in the buttock, thigh or foot
respectively. The presence of bilateral symptoms may indicate
aortic disease, bilateral iliac disease or non-vascular aetiology.
Claudication typically comes on after walking a pain-free
distance (unlike the pain of osteoarthritis etc.) and is worse
when walking fast or uphill, when muscle oxygen requirements
are at their highest. Though reported claudication distances are
notoriously inaccurate as a measure of disease severity, serial
assessment of walking ability over months can be a useful indi-
cator of clinical improvement or deterioration.
Symptoms of chronic PAD (Box 1) generally develop over
months or even years, with a gradual deterioration in pain-free
walking distance. Rapid deterioration of symptoms or sudden
onset of claudication are important warning signs which may
indicate new arterial occlusion.
Critical limb ischaemia
Whilst some patients follow steady progression from asymp-
tomatic PAD to IC and then CLI, this is the exception rather than
the rule. Patients with PAD often have significant co-morbidity
limiting physical activity and may develop CLI without pre-
ceding IC.
229 Ó 2013 Elsevier Ltd. All rights reserved.
 VASCULAR SURGERY e II
Definitions
Peripheral arterial disease (PAD) e Atherosclerosis that leads to
arterial stenosis and occlusion in the major vessels supplying the
lower extremities6
Intermittent claudication (IC) e Ischaemic muscle discomfort in
the lower limb reproducibly produced by exercise and relieved by
rest within 10 min6
Critical limb ischaemia (CLI) e Ulcers, gangrene or ischaemic rest
pain for more than 2 weeks attributable to objectively proven
arterial occlusive disease6
Acute limb ischaemia (ALI) e A sudden decrease in limb perfusion
that threatens viability of the limb6
Box 1
In established CLI the prognosis is poor, so early recognition
and prevention are vital. Approximately 12% of patients with CLI
will require amputation within 3 months of presentation and up
to 25% will die within 1 year.6 Estimated 5-year survival rate for
patients with CLI is 50e60% (worse than many cancers)7 and
these patients require urgent referral for specialist evaluation.
Patients with PAD and diabetes are four times more likely to
develop CLI and require amputation than those without diabetes.
Microvascular dysfunction and poor collateralization of occluded
arteries contributes to reduced peripheral blood flow (Figure 1).6
However, aetiology of ulceration in patients with diabetes is
usually multifactorial with infection and neuropathy playing a
significant role. ABPI readings are often artificially high in dia-
betic patients (due to heavy arterial calcification) and whilst 50%
of diabetic foot ulcers are ischaemia related, other factors
including neuropathy often play a significant role. NICE guide-
lines recommend that patients with diabetes and foot ulceration
Figure 1 (a) Typical presentation of foot ischaemia/infection in diabetes. Note generalized swelling and purulent discharge. (b) Good healing after hallux/
2nd toe amputation (different patient).
SURGERY 31:5
should be seen by a multidisciplinary diabetic foot team within
24 hours.8
Clinical features: ischaemic rest pain and tissue loss (i.e. ul-
ceration or necrosis) are key symptoms of CLI (Figure 2). True
rest pain usually affects the toes or foot of the limb. It is most
pronounced at night when cardiac output is at its lowest and
elevation of the leg prevents gravity from assisting perfusion.
Patients classically describe hanging the affected leg out of bed to
ease symptoms.
Arterial ulcers are typically ‘punched-out’ and have a have a
white base due to the absence of healthy granulation tissue. They
are often found on the dorsum of the foot or digits and usually
associated with multiple stenoses or occlusions in the arterial
tree.
Non-atherosclerotic causes of chronic limb ischaemia
When younger patients present with symptoms of claudication,
non-atherosclerotic vascular causes should be considered.
 Athletic patients: popliteal artery entrapment; iliac artery
endofibrosis
 Male heavy smokers: Buerger’s disease (thromboangiitis
obliterans)
 Pain/pulsatile mass in buttock(s): persistent sciatic
artery
 Young patients with no other risk factors: cystic adven-
titial disease; fibromuscular dysplasia
Differential diagnosis: claudication-type symptoms are not al-
ways caused by atherosclerotic disease and patients with pathol-
ogy of the lumbar spine often experience symptoms similar to
those of PAD e so called ‘spinal claudication’. These patients differ
from those with PAD in that they often report weakness as well as
pain when walking and straight leg raise may reproduce their
symptoms. Osteoarthritis of the hip or knee may also cause pain.
230 Ó 2013 Elsevier Ltd. All rights reserved.
 VASCULAR SURGERY e II

Examination in chronic ischaemia: physical examination

should assess the entire cardiovascular system in order to iden-
tify other manifestations of cardiovascular disease. Blood pres-
sure, heart rate and cardiac rhythm should be evaluated and the
abdomen palpated for evidence of abdominal aortic aneurysm
(AAA). Body mass index (BMI) should be calculated from height
and weight measurements. Limb temperature and capillary refill
time should also be assessed and the feet examined carefully for
signs of ulceration or necrosis, with particular attention to the
heels and interdigital clefts.
All peripheral pulses should be palpated in order to localize
the arterial stenosis/occlusion and identify other pathologies
such as popliteal aneurysms. When the presence of pulses is in
doubt, ankle-brachial pressure index (ABPI) can be measured
using a hand-held Doppler (Box 2). However, whilst ABPI is an
objective means of assessing distal limb perfusion, falsely high
readings are common in patients with diabetes due to heavy
arterial calcification.9
Tissue loss is the cardinal sign of CLI, but clinicians should
look for other signs of chronic ischaemia such as pallor on limb
elevation and hyperaemia when the leg is dependent (Buerger’s
sign). This occurs due to the loss of capillary autoregulation in
the ischaemic limb.
Figure 2 Appearance of a critically ischaemic foot. Note the demarcating,
dry necrosis and skin rubor typical of chronic ischaemia.
ABPI measurements may be supplemented with toe-brachial
pressure index, transcutaneous oxygen assessment or exercise
testing. Patients with mild PAD may have a normal resting
Pain relieved by lumbar flexion (i.e. sitting) ABPI despite a good history of IC. If the ABPI is repeated
 Degenerative lumbar spine disease immediately after exercise a significant pressure drop may be
 Spinal canal stenosis (often associated with leg weakness) identified (a decrease of 15e20% being considered diagnostic
 Lumbar nerve root irritation (may be exacerbated by of PAD).6
straight leg raise)
Investigations
Pain elicited on joint examination All patients with suspected PAD should be screened for cardio-
 Osteoarthritis of hip or knee vascular risk factors.

How to measure ankle-brachial pressure index (ABPI)

Patient should be resting and supine

Place sphygmomanometer cuff just above ankle

Measure systolic blood pressure of dorsalis pedis (DP) and posterior tibial (PT) arteries using a hand-held
Doppler device
Measure systolic blood pressure of the brachial artery (bilaterally) in the same way

ABPI = Highest ankle pressure (DP or PT) on that leg

Highest arm pressure (right or left)
Interpreting results

ABPI: >1.2 Heavy vessel calcification (false elevation of ABPI)

0.9-1.2 Normal range
0.5-0.9 Peripheral arterial disease
<0.5 Critical limb ischaemia*
* Ulceration of the foot may occur at higher ABPIs in patients with diabetes because PAD is often only one component of a multi-factorial aetiology
including infection, neuropathy and microvascular dysfunction.

Box 2

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 VASCULAR SURGERY e II

All patients Examination in acute limb ischaemia

 Random serum glucose (to exclude occult diabetes) In assessing an acutely ischaemic limb, the main objective must
 HbA1c (to assess glycaemic control in diabetes) be to determine the severity and reversibility of ischaemia. As for
 Full blood count (to exclude polycythaemia/anaemia/ any patient with suspected arterial disease, a full cardiovascular
thrombocythaemia) examination should be performed before assessing for evidence
 Serum urea and creatinine (to exclude renal of the ‘six Ps’. Hand-held Doppler should be used to assess
dysfunction) arterial flow if pulses are not readily palpable.
 Serum cholesterol In the initial stages there may be only mild sensorimotor
Patients <50 years old deficit and at this point the limb is likely to be salvageable if
 Thrombophilia screen treated promptly. As ischaemia progresses, there may be signs of
 Serum homocysteine skin mottling or calf tenderness with tense facial compartments.
These are late signs of ischaemia and suggest the limb is at risk if
not treated immediately. Fixed mottling or complete loss of
Acute limb ischaemia
sensorimotor function indicates irreversible ischaemia.
Though PAD frequently manifests as a chronic deterioration of
limb perfusion, it is also the leading cause of acute limb Investigations
ischaemia (ALI), with atherosclerotic plaque rupture or in-situ For those with acute ischaemia, standard preoperative blood
thrombosis (e.g. thrombosed popliteal aneurysm) leading to tests should be performed along with a thrombophilia screen
arterial occlusion. (prior to starting anticoagulation) and a creatine phosphokinase
Embolic occlusion has become less common as the prevalence level to exclude rhabdomyolysis. An ECG should also be done to
of rheumatic heart disease has fallen, but it is still frequently identify potential arrhythmias.
encountered and is usually caused by atrial fibrillation. Emboli
may also arise from aneurysms or atherosclerotic plaques in Imaging
more proximal arteries. Atheroembolism can occur spontane-
Duplex ultrasound is the first-line imaging modality for both
ously, but may also be caused iatrogenically during angioplasty
acute and chronic limb ischaemia, since it is non-invasive,
or bypass surgery (trash foot). This has a worse prognosis than
readily available and has a sensitivity of 84e87% and a speci-
cardiac embolization, since embolectomy and thrombolysis are
ficity of 92e98% compared to angiography.9
less effective and small atheroemboli may pass into very distal
Although digital subtraction angiography (DSA) was tradi-
vessels of the foot.
tionally considered the ‘gold standard’ for detailed arterial
assessment, computed tomography angiography (CTA)
Causes of acute limb ischaemia
(Figure 3) and magnetic resonance angiography (MRA) have
Embolic
largely superseded this due to their non-invasive nature. A meta-
 Atrial fibrillation
analysis of 34 studies comprising 1090 patients, found that MRA
 Mural thrombus (following acute myocardial
was highly accurate for assessment of arterial disease throughout
infarction)
the lower extremity and it is now recommended by NICE as the
 Atherosclerotic embolus
preferred choice of imaging in PAD.10 The role of DSA is now
 Upstream aneurysm
primarily in intervention.
Thrombotic
 Atherosclerosis/plaque rupture
Management of chronic limb ischaemia
 Thrombosed bypass graft
 Thrombosed popliteal aneurysm Risk factor modification
 Prothrombotic states (e.g. malignancy, thrombophilia, Approximately 65% of patients with PAD will also have clinically
polycythaemia) significant cerebral or coronary artery disease and patients with
 Arteritis (e.g. thromboangiitis obliterans, Takayasu’s PAD have a sixfold risk of death due to cardiovascular disease
arteritis) compared to those without PAD.11 More than 10% of patients
 Low flow states (e.g. due to myocardial infarction, with PAD will suffer stroke, myocardial infarction or death
dehydration or sepsis) within 2 years of follow up.12 Risk factor modification is
Rarer causes therefore extremely important in order to reduce the risk of
 Direct trauma life-threatening cardiovascular events as well as preventing
 Compartment syndrome progression of PAD.6
 Dissection Smoking is the most significant modifiable risk factor for
 HIV arteriopathy PAD.6 Smoking cessation is therefore extremely important and is
best achieved through a combination of physician advice, group
Clinical features: patients with embolic occlusion or acute counselling sessions and nicotine replacement therapy (NRT).
thrombosis in an otherwise normal arterial tree typically present The addition of antidepressants such as buproprion has also been
with severe ischaemic symptoms. The classically described signs shown to improve cessation rates.13
of acute ischaemia are the ‘six Ps’ of pain, pallor, pulselessness, For patients with diabetes, glycaemic control is very important
perishing cold, paraesthesia and paralysis, though not all of these since every 1% increase in HbA1c is associated with a 26% increase
may be present in every case. in the risk of PAD.14 PAD also progresses more rapidly in these

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 VASCULAR SURGERY e II
Figure 3 CT-angiogram images showing (a) normal lower limb arteries and (b) heavily diseased arteries with previous femoral to anterior tibial bypass.
patients and they are five to ten times more likely to require major
amputation (i.e. above ankle level) than patients without diabetes.
Hypertension should be treated aggressively and angiotensin
converting enzyme inhibitors (ACEI) may significantly reduce
the risk of cardiovascular events in patients with PAD. b-blockers
can also be used safely by these patients and may reduce peri-
operative cardiovascular events in those requiring surgery.6
A statin should be prescribed to lower cholesterol unless
contraindicated, since cardiac-related mortality is reduced by
approximately 20% with every 1 mmol/litre reduction in low-
density lipoprotein cholesterol, irrespective of initial cholesterol
level.15 Use of fibrates and niacin should be reserved for those
patients who have specific abnormalities of triglycerides or high-
density lipoprotein cholesterol.
All patients with PAD should also be on an antiplatelet agent
and clopidogrel is now considered to be safer and more effective
than aspirin.16 Concurrent use of more than one antiplatelet agent
SURGERY 31:5
is generally not advised for those with simple PAD, but dual an-
tiplatelet therapy may be useful for maintaining graft patency of
prosthetic bypass graft. Warfarin is not routinely advised for pa-
tients with PAD unless they have another indication for its use.
Patients with a BMI greater than 25 kg/m2 should be encouraged
to lose weight and take regular exercise,6 though greatest clinical
benefit is derived through structured exercise programmes (dis-
cussed below).
Management of claudication symptoms
Exercise: exercise regimes involving at least two sessions of
exercise per week may improve a patient’s walking distance by
50e200%. Structured exercise programmes appear to confer
greatest benefit, with those in supervised programmes showing
30e35% greater improvement in walking distance after 3 months.
NICE therefore recommends that all patients with IC should be
offered a supervised exercise programme.10
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 VASCULAR SURGERY e II
For those patients unable to comply with exercise programmes,
mechanical intermittent pneumatic compression of the calf may
offer some benefit, though evidence for this remains limited.
Vasoactive drugs: the two drugs currently available in the UK for
treatment of intermittent claudication are cilostazol and naftidrofuryl
oxalate. Both of these may offer modest improvement in walking
distance, though studies of their efficacy have presented very limited
follow-up data and cost-effectiveness remains questionable.
Though antiplatelet agents (e.g. aspirin) and vasodilators (e.g.
nifedipine) are important for reducing overall cardiovascular
risk, there is little compelling evidence that these drugs offer any
benefit in treating the symptoms of claudication.
Intervention for intermittent claudication
Intervention should be considered when conservative measures
have failed and PAD is severely affecting a patient’s lifestyle or
becoming limb threatening. This may be either endovascular (i.e.
angioplasty or stenting) or surgical. The most suitable treatment
option should be determined on the basis of site/extent of the
lesion, patient fitness and local expertise.
Patients with focal iliac disease are more likely to be offered
endovascular treatment than those with femoral disease, since
intervention at iliac level is more durable (Figure 4). Meta-
analysis has shown that 5-year patency is 79% after iliac an-
gioplasty versus 55% after femoral angioplasty. However,
structured exercise programmes may be just as effective as an-
gioplasty for improving walking distance.6
Surgical bypass is generally reserved for those patients who
have debilitating claudication and a pattern of disease not
amenable to angioplasty.
Intervention for critical limb ischaemia
Patients with CLI typically have multi-level disease and surgical
bypass is often more appropriate, though endovascular tech-
niques may be used as adjuncts to improve flow in vessels
proximal or distal to the bypass. Newer technologies such as
drug-eluting balloons and stents may improve the efficacy of
endovascular techniques. Endovascular techniques to re-open
long-segment occlusions (such as sub-intimal angioplasty) have
also demonstrated encouraging results in expert hands.
TASC guidelines suggest that patients with diffuse aorto-iliac
disease should be treated with surgical bypass (unless other
factors such as co-morbidity prevent this) and 5-year patency of
aorto-bifemoral bypass grafts is over 85% in those with CLI.6
Figure 4 Digital subtraction angiography images taken before (a), during (b) and after (c) angioplasty/stenting of the right common iliac artery.
SURGERY 31:5
Though few studies have compared the efficacy of angioplasty
and surgical bypass in the treatment of severe limb ischaemia,
the BASIL trial (Bypass versus Angioplasty in Severe Ischaemia
of the Leg) found no difference between groups for amputation
free survival, all-cause mortality or quality of life at 2 years,
though the angioplasty group had significantly higher rates of re-
intervention (28% vs. 17%) and many ultimately required sur-
gery. Subgroup analysis from this study suggests that surgery
may be the favoured option for fit patients with usable vein. Vein
is used for the bypass whenever possible, as 5-year primary
patency rates are far higher than with prosthetic grafts (70% vs.
20% for femoro-distal bypass).6
Angioplasty alone may be beneficial for patients with CLI
and infra-inguinal disease who are otherwise too unfit for
bypass. Though long-term patency results are poor, short-term
improvements in distal perfusion may be sufficient to allow
ulcer healing.
When revascularization is unlikely to be successful or the
patient has comorbidities that might prevent them making use of
a salvageable limb, primary amputation may offer the best
quality of life. The knee joint is preserved whenever possible for
the sake of mobility, though this must be balanced with the need
to ensure good wound healing.
Non-surgical management of CLI
Non-surgical treatments are generally considered to have little
long-term benefit and those patients that are unsuitable for
revascularization should be managed symptomatically and un-
dergo amputation as appropriate.
Prostanoids such as iloprost may improve healing of ischae-
mic ulcers as well as reducing pain and amputation rates in those
with CLI. However, the long-term benefit remains unproven and
their use is therefore limited.
Spinal cord stimulation (SCS) may be useful for some patients
and has been shown to improve limb salvage rates at 1 year,
though the cost-effectiveness of this treatment remains in doubt
and it is not widely available There is no clear evidence that
lumbar sympathectomy improves limb salvage for patients with
unreconstructable CLI, though it may be of use in pain control.
Management of acute limb ischaemia
Initial management should involve rapid resuscitation with
oxygen, intravenous fluids and analgesia as necessary. Unfrac-
tionated heparin should be given intravenously (5000 units) and
234 Ó 2013 Elsevier Ltd. All rights reserved.
 VASCULAR SURGERY e II
if the patient is not progressing to surgery immediately a
continuous heparin infusion should be started.
Diagnostic imaging is only appropriate when patients present
with no sensorimotor deficit and the limb is considered to be
viable. If the limb is threatened, imaging is unlikely to change
management and simply delays revascularization.
Surgical revascularization
Embolectomy: once the site of occlusion has been localized clini-
cally, a Fogarty embolectomy catheter can be inserted at femoral
(most common) or popliteal level and passed proximally and distally
to retrieve the embolus. On-table angiography is then performed to
confirm that the vessel has been cleared. If there is evidence of any
residual clot, thrombolysis can be given intraoperatively.
Arterial bypass: embolectomy is sometimes unsuccessful due to
heavy atherosclerosis and these patients will require arterial
bypass. Similarly, thrombosed popliteal aneurysms are not
amenable to embolectomy and femoro-popliteal bypass must be
performed with ligation of the native artery proximal and distal
to the aneurysm to prevent embolization.
Fasciotomy: if the affected limb has been severely ischaemic,
reperfusion often causes significant muscle oedema and four-
compartment fasciotomies should therefore be performed to pre-
vent compartment syndrome. Fasciotomy wounds can be allowed
to heal by secondary intention or undergo split skin grafting.
Catheter-directed thrombolysis
When the limb is not immediately threatened, catheter-directed
thrombolysis (CDT) may be used to try and clear the occlusive
thrombus. Simultaneous thrombectomy (aspiration or mechani-
cal) may also be used to improve clot dissolution. CDT is
particularly useful for patients with occluded prosthetic bypass
grafts for whom surgical re-intervention may be challenging.
Thrombolysis is less invasive than surgery and has the
advantage of clarifying the underlying lesion and allowing an-
gioplasty if necessary. However, it can also be associated with
serious complications such as bleeding, stroke or embolization.
Contraindications to thrombolysis include:
 surgery within 2 weeks
 stroke or neurosurgery within 2 months
 recent gastrointestinal bleeding
 trauma.
The few trials that have compared thrombolysis to surgery in
acute limb ischaemia have failed to show any significant differ-
ence in limb salvage rates and its use should therefore be based
on local expertise and availability.17
Amputation
Up to 10% of individuals with ALI present with irreversible
ischaemia and these patients should undergo primary amputa-
tion of the affected limb. Revascularization should not be
attempted, as the release of toxic metabolites from the ischaemic
tissue is frequently fatal.
Further management
Following revascularization it is important to try and identify the
source of emboli, though in many cases no clear cause will be
SURGERY 31:5
found. All patients with ALI should therefore be anticoagulated
for 3e6 months and those with evidence of thromboembolism
should be considered for longer-term anticoagulation, or anti-
platelet therapy if anticoagulation is contraindicated.6 A
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