Peripheral arterial disease

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acute limb ischaemia

1st line – urgent assessment for revascularisation or amputation

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1st line –

urgent assessment for revascularisation or amputation

Acute limb ischaemia is a medical emergency.[2]

Patients who have sudden decrease in limb perfusion with threatened tissue viability require urgent history and physical examination to determine symptom onset. They need rapid assessment by a vascular surgeon with a view to restoring arterial blood flow as soon as possible.[2] Emergency vascular study assessment should be performed with ankle-brachial index or duplex ultrasound. If there is severe peripheral arterial disease, then the patient should immediately be assessed for aetiology of acute limb ischaemia.[2]

Non-viable limb: these patients will have signs of tissue loss, nerve damage, and sensory loss and will require amputation.

Viable limb: these patients will have no significant tissue loss, nerve damage, or significant sensory loss. Patients should have arterial anatomy defined and undergo revascularisation.

Factors influencing choice of revascularisation strategy include the presence of a neurological deficit, duration of ischaemia, its localisation and patient-specific anatomy, comorbidities, type of conduit (artery or graft), risks related to treatment, and local resource availability.[1][2] [ ]

Plus – antiplatelet therapy

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Plus –

antiplatelet therapy

Treatment recommended for ALL patients in selected patient group

Antiplatelet therapy with aspirin is recommended. Clopidogrel is recommended as an effective alternative antiplatelet therapy to aspirin.

Primary options

aspirin: 75-325 mg orally once daily

clopidogrel: 75 mg orally once daily

Plus – analgesia

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Plus –

analgesia

Treatment recommended for ALL patients in selected patient group

For acute ischaemic pain, paracetamol and an opioid (weak such as codeine, or strong such as morphine) are recommended, depending on the severity of pain. Consult local guidance for selection of an appropriate analgesic regimen.[46][56]

Primary options

paracetamol: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

-- AND --

codeine phosphate: 30-60 mg orally every 4 hours when required, maximum 240 mg/day

morphine sulfate: 10-30 mg orally (immediate-release) every 4 hours when required, titrate dose according to response; 2.5 to 10 mg subcutaneously/intramuscularly/intravenously every 2-6 hours when required, titrate dose according to response

Plus – anticoagulation

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Plus –

anticoagulation

Treatment recommended for ALL patients in selected patient group

In patients with acute limb ischaemia, systemic anticoagulation with unfractionated heparin should be administered, unless contraindicated.

Primary options

heparin: consult specialist for guidance on dose

Plus – risk factor modification

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Plus –

risk factor modification

Treatment recommended for ALL patients in selected patient group

All patients with acute limb ischaemia should have aggressive risk factor modification regardless of their symptoms. This should include guideline-directed management of blood pressure, diabetes, and hyperlipidaemia.[1][2]

Additionally, the presence of specific comorbidities and risk factors increases the risk for major adverse cardiovascular events and major adverse limb events in those with peripheral arterial disease (PAD). Multisociety US guidelines recommend that patients with PAD should be assessed for these risk amplifiers when developing patient-focused treatment recommendations.[2] These risk amplifiers include (in addition to hypertension, dyslipidaemia, and diabetes) chronic kidney disease, depression, atherosclerotic disease in more than one vascular bed, microvascular disease (retinopathy, neuropathy, nephropathy), and older age and geriatric syndromes (frailty, mobility impairment, sarcopenia, malnutrition). Decisions on initial revascularisation versus medical therapy with anticoagulation (unfractionated heparin) and monitoring approach and assessment for amputation will be affected by the presence of comorbidities and risk amplifiers.[2] Co-ordination of care across multispeciality teams is important for management of these patients.

Consider – endovascular revascularisation and intra-arterial thrombolysis

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Consider –

endovascular revascularisation and intra-arterial thrombolysis

Additional treatment recommended for SOME patients in selected patient group

For patients with a viable limb who continue to have symptoms, revascularisation is recommended. Endovascular revascularisation with intra-arterial thrombolysis is often preferred to bypass surgery in patients with severe comorbidities. Initial endovascular techniques include percutaneous catheter-directed thrombolytic therapy, and percutaneous mechanical thrombus extraction or thrombo-aspiration (with or without thrombolysis).[1]

Localised intra-arterial infusion of thrombolytics is used with or without the concomitant use of a mechanical thrombectomy device.[2]

Thrombolytic agents include alteplase, reteplase, and tenecteplase.[2][57] Although there are several comparative studies, no single thrombolytic agent or regimen has emerged as the treatment of choice.[58][59]

Definitive endovascular treatment of any underlying culprit lesion may include percutaneous transluminal angioplasty with balloon dilation or stents.[77][78] [ ]

Primary options

urokinase: consult specialist for guidance on dose

alteplase: consult specialist for guidance on dose

reteplase: consult specialist for guidance on dose

tenecteplase: consult specialist for guidance on dose

Consider – surgical revascularisation

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Consider –

surgical revascularisation

Additional treatment recommended for SOME patients in selected patient group

For patients with a viable limb who continue to have symptoms, revascularisation is recommended. Options for surgical revascularisation include surgical thrombectomy, bypass, and/or arterial repair.[1]

For aortoiliac disease, endovascular revascularisation is frequently the first choice, with surgery reserved for extensive obstructions and lesions treated unsuccessfully with an endovascular procedure, but individual patient factors including treatment preferences should inform the selection of revascularisation technique.[1][2]

Surgical endarterectomy or a hybrid approach (surgical and endovascular procedures in combination) is frequently performed for common femoral artery lesions.[1][2] Common femoral endarterectomy has a high patency rate but may be associated with significant complications.[79]

For femoropopliteal artery stenosis, endovascular therapy is frequently performed but surgical endarterectomy is reasonable if perioperative risk is acceptable and technical factors suggest advantages over endovascular approaches.[1][2]

For infrapopliteal artery lesions, endovascular treatment has been limited to threatened limb loss only, but evidence to support either surgical or endovascular approaches is lacking.[2] Surgical revascularisation to tibial targets has a primary patency at 1, 3, and 5 years of 66%, 59%, and 55%, respectively.[80]

Consider – amputation

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Consider –

amputation

Additional treatment recommended for SOME patients in selected patient group

If part of a limb is clearly non-viable from the outset or attempts at revascularisation should fail, amputation is required. Careful consideration of the most appropriate type and level of amputation should be made in consultation with the patient, bearing in mind factors such as likelihood of successful healing, patient motivation and social circumstances, presence of comorbidities, and the patient's potential functional outcomes with an appropriate prosthesis, if required.

ONGOING

claudication (not lifestyle-limiting)

1st line – antiplatelet ± antithrombotic therapy

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1st line –

antiplatelet ± antithrombotic therapy

Antiplatelet therapy with aspirin is recommended.[2] Clopidogrel is an effective alternative to aspirin.

Evidence suggests that antiplatelet therapy significantly reduces cardiovascular event rates in patients with claudication.[89]

Use of low-dose rivaroxaban (a direct oral anticoagulant [DOAC]) combined with low-dose aspirin reduces ischaemic events compared with use of aspirin alone in patients with symptomatic peripheral arterial disease (PAD) and can be considered for selected patients without other indications for anticoagulation (e.g., atrial fibrillation). However, this combination is associated with a higher risk of major bleeding.[1][2][55]

Co-prescription of a proton-pump inhibitor may be recommended to reduce the risk of an upper gastrointestinal bleed, especially in patients aged 75 years or older.[90]

Considerations for comorbidity: in patients with PAD and atrial fibrillation, antiplatelet therapy may not be recommended for many patients with stable PAD as they will be on long-term anticoagulant therapy.[1][87] For guidance on anticoagulant therapy for these patients, see Established atrial fibrillation.

Primary options

aspirin: 75-325 mg orally once daily

clopidogrel: 75 mg orally once daily

Secondary options

aspirin: 75 mg orally once daily

and

rivaroxaban: 2.5 mg orally twice daily

Plus – exercise

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Plus –

exercise

Treatment recommended for ALL patients in selected patient group

Exercise therapy has been shown to improve walking time and relieve symptoms in multiple studies (limited quality). A supervised exercise training programme consists of 30-45 minutes per session, 3 times a week for 12 weeks.[2]

Plus – risk factor modification

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Plus –

risk factor modification

Treatment recommended for ALL patients in selected patient group

Patients with peripheral arterial disease (PAD) have significantly increased risk of cardiovascular mortality and morbidity, and it is crucial to modify their cardiovascular risk factors. All PAD patients should have aggressive risk factor modification, regardless of their symptoms. This should include: control of blood pressure; guideline-directed management for patients with diabetes; lipid-lowering therapy; cessation of smoking; dietary advice to reduce cardiovascular disease risk and control weight; and increased exercise.[1][2]

Blood pressure control: antihypertensive therapy is recommended in patients with PAD and hypertension to reduce risk of major adverse cardiovascular events. Multisociety US guidelines recommend a target blood pressure of <130/80 mmHg.[2] European Society of Cardiology guidelines recommend a target systolic blood pressure of 120-129 mmHg, if tolerated.[1] No one class of antihypertensive medication or strategy is superior for lowering blood pressure in PAD; however, ACE inhibitors or angiotensin-II receptor antagonists have been shown to reduce risk of cardiovascular events and are generally preferred.[1][2]

Lipid-lowering therapy: high-intensity statin therapy is recommended in all patients with PAD to reduce major adverse cardiovascular events and major adverse limb events. Multisociety US guidelines recommend a target low-density lipoprotein cholesterol (LDL-C) level of <1.8 mmol/L (<70 mg/dL).[2] European Society of Cardiology guidelines recommend a target of <1.4 mmol/ L (<55 mg/dL).[1] In those with PAD on maximally tolerated statin therapy and with LDL-C below target, additional lipid-lowering therapy with ezetimibe or a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be considered.[1][2] In patients who have high-risk PAD and elevated triglycerides despite lifestyle changes and statin therapy, European Society of Cardiology guidelines provide a weak recommendation for addition of icosapent ethyl.[1] The US National Lipid Association also recommends addition of icosapent ethyl for patients aged 45 years or older with established atherosclerotic cardiovascular disease and elevated triglycerides who are already on high-intensity or maximally tolerated statin therapy.[86]

Diabetes management: a guideline-based programme of pharmacological and non-pharmacological therapies for patients with diabetes and PAD is recommended, including glycaemic control, foot care and ulcer prevention, management of diet and weight, and control of cardiovascular risk factors.[2] In those with PAD and type 2 diabetes mellitus, glycaemic control with a glucagon-like peptide-1 (GLP-1) receptor agonist (e.g., liraglutide, semaglutide) and/or a sodium-glucose cotransporter-2 (SGLT2) inhibitor (e.g., canagliflozin, dapagliflozin, empagliflozin) may be preferred, as they have been shown to reduce the risk of major adverse cardiovascular events.[1][2] Co-ordination of care is essential in patients with diabetes and PAD.[2]

Additionally, the presence of specific comorbidities and risk factors increases the risk for major adverse cardiovascular events and major adverse limb events in those with PAD. Multisociety US guidelines recommend that patients with PAD should be assessed for these risk amplifiers when developing patient-focused treatment recommendations.[2] These risk amplifiers include (in addition to hypertension, dyslipidaemia, and diabetes) chronic kidney disease, depression, atherosclerotic disease in more than one vascular bed, microvascular disease (retinopathy, neuropathy, nephropathy), and older age and geriatric syndromes (frailty, mobility impairment, sarcopenia, malnutrition).

claudication (lifestyle-limiting)

1st line – antiplatelet ± antithrombotic therapy

Back

1st line –

antiplatelet ± antithrombotic therapy

Antiplatelet therapy with aspirin is recommended.[2] Clopidogrel is an effective alternative to aspirin.

Evidence suggests that antiplatelet therapy significantly reduces cardiovascular event rates in patients with claudication.[89]

Co-prescription of a proton-pump inhibitor may be recommended to reduce the risk of an upper gastrointestinal bleed, especially in patients aged 75 years or older.[90]

Considerations for comorbidity: in patients with PAD and atrial fibrillation (AF), antiplatelet therapy may not be recommended for many patients with stable PAD as they will be on long-term anticoagulant therapy.[1][87] In patients with PAD and AF who are undergoing revascularisation (endovascular or surgical), addition of a single antiplatelet agent (preferably clopidogrel) to long-term oral anticoagulation may be considered temporarily (1-3 months), taking bleeding risk into account.[1][87][88]Kumbhani DJ, Cannon CP, Beavers CJ, et al. 2020 ACC expert consensus decision pathway for anticoagulant and antiplatelet therapy in patients with atrial fibrillation or venous thromboembolism undergoing percutaneous coronary intervention or with atherosclerotic cardiovascular disease: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021 Feb 9;77(5):629-58. For guidance on anticoagulant therapy for these patients, see Established atrial fibrillation.

Primary options

aspirin: 75-325 mg orally once daily

clopidogrel: 75 mg orally once daily

Secondary options

aspirin: 75 mg orally once daily

and

rivaroxaban: 2.5 mg orally twice daily

Plus – exercise

Back

Plus –

exercise

Treatment recommended for ALL patients in selected patient group

Patients with lifestyle-limiting symptoms should undergo a supervised exercise programme for 3 months.[2] Exercise therapy has been shown to improve walking time and relieve symptoms in multiple studies (limited quality). A supervised exercise training programme consists of 30-45 minutes per session, 3 times a week for 12 weeks.[2]

Plus – symptom relief

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Plus –

symptom relief

Treatment recommended for ALL patients in selected patient group

Symptom relief can be achieved with cilostazol or naftidrofuryl.[62][63]

Cilostazol may improve pain-free walking distance in patients with intermittent claudication. However, participants taking cilostazol had higher odds of experiencing headache.[64][65] One meta-analysis demonstrated that the addition of cilostazol to antiplatelet therapy after peripheral vascular interventions is associated with a reduced risk of restenosis, amputation, and target lesion revascularisation.[66] Cilostazol also reduces angiographic restenosis after percutaneous transluminal angioplasty and stenting for femoropopliteal lesions.[67]

Cilostazol is contraindicated in patients with heart failure of any severity.

Patients taking cilostazol should be assessed for benefit 3 months after starting treatment, and treatment ceased if there is not a clinically-relevant improvement in walking distance.

Patients with intermittent claudication may improve their walking distance with naftidrofuryl therapy.[68] Naftidrofuryl was shown to be more effective than cilostazol in a systematic review.[69]

Primary options

cilostazol: 100 mg orally twice daily

naftidrofuryl: 200 mg orally three times daily

Plus – risk factor modification

Back

Plus –

risk factor modification

Treatment recommended for ALL patients in selected patient group

Lipid-lowering therapy: high-intensity statin therapy is recommended in all patients with PAD to reduce major adverse cardiovascular events and major adverse limb events. Multisociety US guidelines recommend a target low-density lipoprotein cholesterol (LDL-C) level of <1.8 mmol/L (<70 mg/dL).[2] European Society of Cardiology guidelines recommend a target of <1.4 mmol/L (<55 mg/dL).[1] In those with PAD on maximally tolerated statin therapy and with LDL-C below target, additional lipid-lowering therapy with ezetimibe or a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be considered.[1][2] In patients who have high-risk PAD and elevated triglycerides despite lifestyle changes and statin therapy, European Society of Cardiology guidelines provide a weak recommendation for addition of icosapent ethyl.[1] The US National Lipid Association also recommends addition of icosapent ethyl for patients aged 45 years or older with established atherosclerotic cardiovascular disease and elevated triglycerides who are already on high-intensity or maximally tolerated statin therapy.[86]

Consider – revascularisation

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Consider –

revascularisation

Additional treatment recommended for SOME patients in selected patient group

Patients with lifestyle-limiting claudication who have had no improvement with exercise and symptom relief should be referred to a vascular specialist to have their arterial anatomy defined and assessed. One Cochrane review found that revascularisation does not provide significant benefits compared with exercise therapy alone in terms of functional performance or quality of life; however, revascularisation in combination with a conservative therapy of supervised exercise or pharmacotherapy may result in greater improvements compared with conservative therapy alone.[70][71] Intervention for claudication should be carefully considered, as there is potential for complication from any procedure, and the natural history of claudication is not aggressive.

Endovascular techniques include percutaneous transluminal angioplasty with balloon dilation, stents, atherectomy, laser, cutting balloons, and drug-coated balloons.[77][78] [ ]

chronic limb-threatening ischaemia (CLTI)

1st line – assessment for revascularisation

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1st line –

assessment for revascularisation

Patients with critical limb ischaemia symptoms (ischaemic rest pain, gangrene, non-healing wounds/foot and leg ulcers; symptoms present for more than 2 weeks) should be referred to a vascular specialist to have their arterial anatomy defined and assessed.

Consider risk stratification based on the Wound, Ischemia, and Foot Infection (WiFi) score.[51]

Current evidence has not yet established whether bypass surgery or endovascular intervention is superior for initial treatment of critical limb ischaemia, although many operators have adopted an 'endovascular first' strategy.[84][85] Care must be individualised to the patient.

Plus – antiplatelet ± antithrombotic therapy

Back

Plus –

antiplatelet ± antithrombotic therapy

Treatment recommended for ALL patients in selected patient group

Antiplatelet therapy with aspirin is recommended.[2] Clopidogrel is an effective alternative to aspirin.

Evidence suggests that antiplatelet therapy significantly reduces cardiovascular event rates in patients with claudication.[89]

Co-prescription of a proton-pump inhibitor may be recommended to reduce the risk of an upper gastrointestinal bleed, especially in patients aged 75 years or older.[90]

Primary options

aspirin: 75-325 mg orally once daily

clopidogrel: 75 mg orally once daily

Secondary options

aspirin: 75 mg orally once daily

and

rivaroxaban: 2.5 mg orally twice daily

Plus – risk factor modification

Back

Plus –

risk factor modification

Treatment recommended for ALL patients in selected patient group

Lipid-lowering therapy: high-intensity statin therapy is recommended in all patients with PAD to reduce major adverse cardiovascular events and major adverse limb events. Multisociety US guidelines recommend a target low-density lipoprotein cholesterol (LDL-C) level of <1.8 mmol/L (<70 mg/dL).[2] European Society of Cardiology guidelines recommend a target of <1.4 mmol/L (<55 mg/dL).[1] In those with PAD on maximally tolerated statin therapy and with LDL-C below target, additional lipid-lowering therapy with ezetimibe or a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be considered.[1][2] In patients who have high-risk PAD and elevated triglycerides despite lifestyle changes and statin therapy, European Society of Cardiology guidelines provide a weak recommendation for addition of icosapent ethyl.[1] The US National Lipid Association also recommends addition of icosapent ethyl for patients aged 45 years or older with established atherosclerotic cardiovascular disease and elevated triglycerides who are already on high-intensity or maximally tolerated statin therapy.[86]

Consider – endovascular revascularisation

Back

Consider –

endovascular revascularisation

Additional treatment recommended for SOME patients in selected patient group

Endovascular techniques include: balloon dilation (angioplasty); stents; and atherectomy.

These techniques continue to evolve and now include covered stents, drug-eluting stents, cutting balloons, and drug-coated balloons.[91] [ ]

The technique chosen will relate to lesion characteristics (e.g., anatomical location, lesion length, degree of calcification) and operator experience.

For infrapopliteal artery lesions, endovascular treatment has been limited to threatened limb loss only, but evidence to support either surgical or endovascular approaches is lacking.[2]

Consider – surgical revascularisation

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Consider –

surgical revascularisation

Additional treatment recommended for SOME patients in selected patient group

Bypass surgery is one of the mainstay treatments for patients with critical lower limb ischaemia. It may confer improved patency rates up to 1 year but there may be longer hospital stay and peri-interventional complications, and it is less suitable than endovascular treatment in high-risk surgical patients.[92]

Consider – spinal cord stimulation

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Consider –

spinal cord stimulation

Additional treatment recommended for SOME patients in selected patient group

In patients with inoperable chronic critical limb ischaemia facing amputation of the leg, spinal cord stimulation may be a helpful treatment option in addition to standard conservative treatment. There is evidence that spinal cord stimulation is associated with higher rates of limb salvage and more prominent pain relief compared with standard conservative treatment alone.[74][93] [ ]

Consider – autologous bone marrow stem cell transplantation

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Consider –

autologous bone marrow stem cell transplantation

Additional treatment recommended for SOME patients in selected patient group

There is some evidence for this as an option for patients with critical limb ischaemia.[75] However, other studies have failed to show benefit.[76]

Consider – amputation

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Consider –

amputation

Additional treatment recommended for SOME patients in selected patient group

Patients with critical limb ischaemia who are unsuitable for revascularisation will be those unable to walk before the episode of critical limb ischaemia, and who have a limited life expectancy.

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Peripheral arterial disease

Treatment algorithm

acute limb ischaemia

urgent assessment for revascularisation or amputation

antiplatelet therapy

Primary options

analgesia

Primary options

anticoagulation

Primary options

risk factor modification

endovascular revascularisation and intra-arterial thrombolysis

Primary options

surgical revascularisation

amputation

claudication (not lifestyle-limiting)

antiplatelet ± antithrombotic therapy

Primary options

Secondary options

exercise

risk factor modification

claudication (lifestyle-limiting)

antiplatelet ± antithrombotic therapy

Primary options

Secondary options

exercise

symptom relief

Primary options

risk factor modification

revascularisation

chronic limb-threatening ischaemia (CLTI)

assessment for revascularisation

antiplatelet ± antithrombotic therapy

Primary options

Secondary options

risk factor modification

endovascular revascularisation

surgical revascularisation

spinal cord stimulation

autologous bone marrow stem cell transplantation

amputation