Peripheral arterial disease

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Lower-limb PAD is systemic atherosclerotic disease. Leg symptoms matter, but myocardial infarction, stroke and cardiovascular death drive much of the long-term risk.

Intermittent claudication is reproducible exertional muscle pain that resolves within minutes of rest. Chronic limb-threatening ischaemia adds rest pain, tissue loss or gangrene and requires limb-salvage assessment.

Acute limb ischaemia is a sudden fall in perfusion caused by embolus, thrombosis, graft/stent occlusion or trauma. Neurological deficit marks a threatened limb and shortens the safe window.

Anatomical imaging is not required merely to label stable PAD; it is ordered when diagnosis remains uncertain or revascularisation is being planned.

Key points

Suspect PAD with exertional calf, thigh or buttock pain relieved by rest, non-healing leg/foot wounds, rest pain, gangrene, absent pulses or before leg compression/intervention.
Measure ABPI with Doppler after supine rest: use the highest ankle artery pressure in each leg divided by the highest brachial pressure.
ABPI 0.90 or lower supports PAD, but a normal or high ABPI does not exclude disease in diabetes or CKD because calcified vessels may be incompressible.
Stable intermittent claudication is treated first with smoking cessation, lipid/BP/diabetes management, antithrombotic secondary prevention and supervised exercise.
NICE suggests supervised exercise for 2 hours weekly for 3 months, encouraging exercise to maximal claudication pain within a structured programme.
Lifestyle-limiting claudication despite risk-factor management and supervised exercise warrants vascular assessment; duplex is first-line imaging when revascularisation is being considered.
Chronic limb-threatening ischaemia means ischaemic rest pain, non-healing wound or gangrene; it needs urgent vascular-team assessment and revascularisation planning.
Acute limb ischaemia can cause irreversible nerve and muscle injury within hours; do not send a threatened limb through a slow outpatient pathway.
Do not perform major amputation until a vascular multidisciplinary team has considered every revascularisation option, except when immediate life-saving source control is necessary.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Systemic atherosclerosis

Lipid-rich plaque progressively narrows lower-limb arteries. Smoking, diabetes, hypertension, dyslipidaemia, increasing age and chronic kidney disease accelerate endothelial injury and plaque development.

Acute local thrombosis

A diseased artery, bypass graft or stent can thrombose suddenly when flow is already limited. The abrupt fall in perfusion produces acute rather than stable limb ischaemia.

Arterial embolism

Thrombus from the heart or proximal aorta can lodge in a limb artery that was previously patent. Sudden severe symptoms with little preceding claudication support embolic occlusion.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Arterial lumen narrows
Atherosclerotic plaque and remodelling reduce conduit artery diameter and limit the ability to increase blood flow when working skeletal muscle needs more oxygen.
2
Exertional ischaemia causes claudication
Walking raises muscle oxygen demand beyond the restricted supply, causing reproducible ache or cramp. Rest lowers demand, allowing symptoms to settle within minutes.
3
Resting perfusion becomes inadequate
Advanced multilevel disease can no longer meet basal tissue requirements. Forefoot rest pain, non-healing ulceration and gangrene mark chronic limb-threatening ischaemia.
4
Sudden occlusion threatens tissue
Embolism or thrombosis abruptly removes perfusion before collaterals can compensate. Nerves and muscle become dysfunctional, making sensory loss or weakness signs of an immediately threatened limb.
5
Disease extends beyond the limb
The same atherosclerotic process commonly affects coronary and cerebral arteries. Myocardial infarction and stroke therefore account for substantial long-term risk in peripheral arterial disease.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Intermittent claudication

Predictable calf, thigh or buttock ache/cramp on walking that resolves with rest; pulse reduction, bruits, cool skin and trophic change support arterial disease.

Chronic limb-threatening ischaemiaRed flag

Ischaemic rest pain, non-healing ulcer for at least 2 weeks or gangrene. Haemodynamic support includes ankle pressure below 50 mmHg, toe pressure below 30 mmHg or transcutaneous oxygen below 30 mmHg, interpreted with the whole clinical picture.

Acute limb ischaemiaRed flag

Sudden pain, pallor, pulselessness, paraesthesia, perishing cold and paralysis. Sensory loss or muscle weakness means an immediately threatened limb needing emergency revascularisation.

Infected or wet gangreneRed flag

Spreading infection, systemic toxicity, gas, wet necrosis or sepsis requires emergency vascular and surgical source-control assessment alongside antibiotics.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Vascular examination and handheld-Doppler ABPIFirst step
Why
Confirm haemodynamic PAD and document baseline severity.
Interpretation and limitations
ABPI 0.90 or lower supports PAD; very low values suggest severe disease. High/incompressible or apparently normal values in diabetes/CKD require caution.
02
Toe pressure/toe-brachial index or pulse-volume/waveform testing
Why
Clarify perfusion when ABPI is unreliable because of arterial calcification.
Interpretation and limitations
Toe pressure below 30 mmHg supports severe ischaemia/CLTI; waveform and wound context remain important.
03
FBC, U&E/eGFR, HbA1c, lipid profile; ECG and cardiovascular assessment as indicated
Why
Identify anaemia, renal risk, diabetes and modifiable systemic atherosclerotic risk.
Interpretation and limitations
Results guide statin, BP/diabetes treatment and contrast/procedural planning rather than replacing limb assessment.
04
Duplex ultrasoundFirst line
Why
First-line anatomical imaging when revascularisation is being considered.
Interpretation and limitations
Maps stenosis/occlusion and flow; if further detail is needed, NICE prefers contrast-enhanced MRA, with CTA when MRA is contraindicated or not tolerated.
05
CTA/MRA for chronic disease
Why
Plan endovascular or surgical reconstruction after duplex.
Interpretation and limitations
Select according to renal function, implant compatibility, calcification and the intended intervention.
06
Emergency CTA or immediate catheter angiography for acute limb ischaemia
Why
Define the occlusion and treatment route.
Interpretation and limitations
Image only if it will not delay revascularisation in an immediately threatened limb; Rutherford neurological findings determine urgency.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Neurogenic claudication

Lumbar spinal stenosis causes leg pain or weakness related to posture and spinal extension. Relief usually requires sitting or flexion rather than simply stopping, and pulses remain palpable.

Venous claudication

Venous outflow obstruction produces bursting pain, heaviness and swelling during exercise, often resolving slowly with elevation. Arterial pulses and foot temperature are usually preserved.

Musculoskeletal pain

Arthritis, tendon disease or muscle injury produces pain linked to particular movements or local tenderness rather than a reproducible walking distance. Vascular examination is generally normal.

Peripheral neuropathy

Neuropathy causes burning, numbness or altered sensation that is not consistently relieved by rest. Pulses may remain present, although diabetes can produce neuropathy and arterial disease together.

Deep-vein thrombosis

DVT typically causes an acutely swollen, warm and tender limb rather than a cold, pale or pulseless one. Venous ultrasound and arterial examination distinguish the pathways.

Additional chapter-specific clues

Possible non-atherosclerotic or alternative cause

Young age, inflammatory signs, popliteal entrapment pattern, blue toe with pulses, venous claudication, neuropathic pain or spinal symptoms should broaden the differential and prompt specialist testing.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01NICE preferredStable intermittent claudicationFirst stepPreferredExertional limb symptoms without rest pain, ulcer, gangrene or acute neurological deficit.

1Offer smoking cessation, supervised exercise, healthy weight/diet support and management of BP and diabetes; give high-intensity statin and appropriate antithrombotic secondary prevention.
2Offer a supervised programme, aiming for about 2 hours of supervised exercise weekly for 3 months and exercise to maximal claudication pain when safe.
3If symptoms remain substantially lifestyle limiting after risk-factor management and exercise, refer for vascular assessment. Use duplex first when revascularisation is considered.
4Offer angioplasty when imaging is suitable and conservative treatment has failed. Consider bypass for severe lifestyle-limiting disease when angioplasty is unsuitable or has failed; use autologous vein for infra-inguinal bypass where possible.
5Naftidrofuryl is a later option only when supervised exercise has not produced satisfactory improvement and the person does not want vascular referral; review at 3–6 months and stop if no worthwhile benefit.

02NICE urgentChronic limb-threatening ischaemiaRest pain, non-healing ulcer or gangrene.

1Refer urgently to the vascular multidisciplinary team for limb staging, infection control, analgesia, pressure relief/wound care and revascularisation assessment.
2Offer endovascular or bypass revascularisation according to anatomy, conduit, comorbidity and patient preference; do not proceed to major amputation until all revascularisation options have been considered.
3Treat pain initially with paracetamol, adding an opioid if required; involve a pain service when pain remains severe or treatment causes unacceptable adverse effects. Do not let analgesia delay limb salvage.
4Wet gangrene or sepsis requires emergency admission, broad-spectrum antibiotics per the diabetic-foot/soft-tissue infection pathway and urgent source control.

03Emergency / protocol-dependentAcute limb ischaemiaSudden arterial perfusion loss, especially sensory or motor deficit.

1Call vascular surgery immediately, keep the limb dependent and protected, obtain IV access, give titrated analgesia and correct hypovolaemia, acidosis and hyperkalaemia.
2PreferredAlternativeUnless contraindicated, give unfractionated heparin 5,000 units IV or 70–100 units/kg IV, then start an infusion adjusted to the local aPTT/anti-Xa protocol. An ESC alternative is enoxaparin 1 mg/kg subcutaneously every 12 hours when appropriate, but UFH is commonly preferred when urgent procedures are likely.
3A viable or marginally threatened limb can undergo urgent imaging followed by catheter-directed or surgical treatment. An immediately threatened limb with motor deficit needs emergency revascularisation and imaging must not create delay.
4An irreversibly ischaemic limb requires senior vascular assessment for amputation or palliation; reperfusion of dead muscle risks fatal hyperkalaemia and acidosis.

04NICE secondary preventionReduce systemic cardiovascular riskConfirmed symptomatic PAD.

1Offer atorvastatin 80 mg once daily unless interactions, high adverse-effect risk or preference justify a lower dose; aim for LDL cholesterol 2.0 mmol/L or lower or non-HDL 2.6 mmol/L or lower for secondary prevention.
2Clopidogrel 75 mg once daily is a NICE-approved antiplatelet option for PAD. Assess bleeding, hepatic disease and interactions.
3AlternativeFor selected symptomatic PAD at high ischaemic risk, consider rivaroxaban 2.5 mg twice daily plus aspirin 75–100 mg once daily after explicit bleeding-risk assessment. This is an alternative antithrombotic strategy, not an automatic addition to clopidogrel.
4Treat hypertension and diabetes, support smoking cessation and assess coronary/cerebrovascular symptoms.

Key medicines and prescribing safety7 treatments · regimens, roles and cautions

NICE-approved antiplatelet option for prevention of occlusive vascular events in symptomatic PAD.

Clopidogrel

75 mg orally once daily.

Active pathological bleeding and severe hepatic impairment are contraindications; review bleeding risk, bruising, interacting anticoagulants/antiplatelets and planned procedures.

High-intensity lipid lowering for established cardiovascular disease including PAD.

Atorvastatin

80 mg orally once daily for secondary prevention; use a lower dose when interactions, high adverse-effect risk or patient preference make 80 mg unsuitable.

Check baseline liver enzymes; review myalgia/weakness, CYP3A4 interactions, pregnancy and severe liver disease.

NICE option for selected symptomatic PAD at high ischaemic risk after bleeding-risk discussion.

Rivaroxaban plus aspirin

Rivaroxaban 2.5 mg orally twice daily plus aspirin 75–100 mg orally once daily.

Avoid active clinically significant bleeding. Rivaroxaban is not recommended if Cockcroft–Gault creatinine clearance is below 15 mL/min and requires caution at 15–29 mL/min; assess age, hepatic function, previous bleeding, interactions and peri-procedural interruption.

Restricted NICE option for intermittent claudication only after supervised exercise is unsatisfactory and vascular referral is declined.

Naftidrofuryl oxalate

100–200 mg orally three times daily with meals for at least 3 months; swallow with at least a full glass of water. Review at 3–6 months and stop if no meaningful symptomatic benefit.

Avoid with hyperoxaluria or recurrent calcium-containing renal stones; maintain fluid intake. It does not replace secondary prevention or revascularisation when limb threat exists.

ESC/ESVS immediate anticoagulation in acute limb ischaemia while urgent revascularisation is organised; titrate the infusion using the receiving vascular service's aPTT or anti-Xa assay.

Unfractionated heparin

5,000 units IV bolus or 70–100 units/kg IV, followed by infusion titrated to aPTT/anti-Xa according to the receiving vascular protocol.

Withhold/modify for active major bleeding, previous HIT or another overriding contraindication; monitor platelets, haemoglobin, aPTT/anti-Xa and bleeding.

Baseline analgesia for chronic limb-threatening ischaemic pain while urgent vascular treatment proceeds.

Paracetamol

1 g orally every 4–6 hours when required, maximum 4 g in 24 hours; use a lower maximum in low body weight, frailty, malnutrition or liver disease.

Avoid duplicate paracetamol-containing products. Worsening or analgesia-resistant pain can indicate progression of ischaemia and needs urgent reassessment.

Titrated rescue analgesia for severe acute ischaemic pain while revascularisation is organised; it does not replace treatment of the threatened limb.

Morphine sulfate injection

A licensed adult IV example is 2.5–10 mg given slowly over 4–5 minutes, followed by response-led monitored reassessment before any further dose.

Reduce and titrate cautiously in older, frail, respiratory-impaired, hepatic or renal-impaired patients. Monitor consciousness, respiratory rate, oxygenation and BP; have naloxone and airway support available.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Chronic limb-threatening ischaemia

Progressive arterial insufficiency causes rest pain, ulceration or gangrene. Without urgent limb-salvage assessment, tissue loss can advance and make amputation more likely.

Acute limb ischaemia

Sudden thrombosis or embolism can rapidly injure nerves and muscle. Delay after sensory or motor loss risks irreversible necrosis, reperfusion injury and limb loss.

Wound infection and sepsis

Poor perfusion impairs immune delivery and wound healing. Ischaemic ulcers or wet gangrene can become infected, requiring antimicrobial treatment, source control and urgent vascular review.

Myocardial infarction and stroke

Peripheral arterial disease marks widespread atherosclerosis rather than an isolated leg disorder. Coronary or cerebral plaque events drive major long-term morbidity and cardiovascular mortality.

Loss of mobility and conditioning

Claudication can reduce walking, independence and participation in exercise. Progressive inactivity worsens physical conditioning and may make cardiovascular risk-factor control more difficult.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Document walking distance, rest pain, wound dimensions, infection, Doppler signals and pulse/neurological findings; deterioration overrides routine follow-up.
After acute revascularisation, monitor limb perfusion, compartment syndrome, creatine kinase, potassium, acid-base status, renal function and reperfusion injury.
For antithrombotics, monitor clinical bleeding and FBC/renal/hepatic function at baseline and intervals determined by risk; coordinate peri-procedural plans.
Check lipids about 2–3 months after starting/changing statin and assess adherence and adverse effects; use NICE secondary-prevention lipid targets.
Review naftidrofuryl after 3–6 months and stop if there is no symptomatic improvement.
Foot protection, footwear, podiatry and rapid wound review are especially important in diabetes or neuropathy.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

PAD is a cardiovascular diagnosis

A modest leg symptom can coexist with high MI and stroke risk; antithrombotic, statin, BP and smoking treatment are core therapy, not extras.

A normal ABPI may be falsely reassuring

Medial calcification in diabetes and CKD makes ankle arteries incompressible. Toe pressures and Doppler waveforms can reveal severe disease.

Neurology times the limb

Paraesthesia and especially motor weakness signal threatened tissue and move the patient from urgent imaging to emergency revascularisation.

Pain at rest is not claudication

Nocturnal forefoot pain relieved by dependency, ulceration or gangrene suggests CLTI and should not be managed with exercise alone.

Revascularisation follows goals and anatomy

For claudication it is for persistent lifestyle limitation after exercise; for CLTI it is limb salvage and should be considered before major amputation.

11Common pitfallsFrequent interpretation and management errors.

01
Excluding PAD because ABPI is normal or high in a person with diabetes and a non-healing ulcer.
02
Prescribing supervised exercise for rest pain, tissue loss or acute ischaemia instead of urgent vascular referral.
03
Delaying heparin and vascular contact in acute limb ischaemia while waiting for routine imaging.
04
Adding rivaroxaban plus aspirin automatically on top of clopidogrel without a defined procedural or specialist indication.
05
Using naftidrofuryl as a substitute for exercise, secondary prevention or appropriate revascularisation.
06
Proceeding to major amputation before multidisciplinary revascularisation review when the patient is stable enough for it.