Peripheral arterial disease

Peripheral arterial disease (PAD) results from progressive atherosclerotic narrowing or occlusion of the arteries supplying the lower limbs. Reduced arterial perfusion may be sufficient at rest in early disease, but inadequate during exercise, when skeletal muscle oxygen demand rises. This produces the characteristic symptom of intermittent claudication.

Intermittent claudication is usually described as cramping, aching or tightness in the calf, thigh or buttock that develops during walking and is relieved by rest. Calf pain is most common, while aortoiliac disease may present with thigh, hip or buttock discomfort. In men, erectile dysfunction may occasionally be an additional clue to aortoiliac arterial disease, particularly when it occurs alongside buttock or thigh claudication and reduced femoral pulses.

However, many patients do not describe pain clearly. They may say they have ‘slowed down’, avoid hills, stop more often when shopping or can no longer keep up with family members.

At the severe end of the spectrum is chronic limb-threatening ischaemia (CLTI), where perfusion is insufficient even at rest. This may present with rest pain, non-healing ulcers, gangrene or tissue loss. Acute limb ischaemia is different: it is a sudden reduction in limb perfusion, usually presenting with abrupt onset of pain, pallor, coldness, sensory disturbance or weakness, and requires emergency referral.

Who is at risk?

The strongest risk factors for PAD are smoking and diabetes.^1–3,5 Smoking increases the risk of developing PAD and accelerates disease progression. Diabetes is associated with more distal arterial disease, arterial calcification, neuropathy, impaired wound healing and increased risk of ulceration and limb-threatening complications.^1–3,5

Other important risk factors include increasing age, hypertension, dyslipidaemia, CKD, obesity, physical inactivity and established atherosclerotic cardiovascular disease. ^1–3,5 Although PAD has often been perceived as predominantly affecting men, prevalence is similar or higher in women at older ages. Women are also more likely to be underdiagnosed or misdiagnosed and may present with atypical symptoms rather than classic intermittent claudication.^7,8

Recognising PAD in primary care

A careful history remains the most important part of assessment. Ask where the discomfort occurs, how far the patient can walk before it starts, whether it is reproducible and how quickly it resolves with rest. Intermittent claudication usually settles within a few minutes of stopping. Symptoms that persist after rest, occur at night or are relieved by hanging the leg over the side of the bed are more concerning and should raise suspicion of CLTI.

Clinical examination should include inspection of both legs and feet, looking for colour change, dependent rubor, pallor on elevation, cool skin, ulceration, pressure damage or tissue loss. Palpate the femoral, popliteal, posterior tibial and dorsalis pedis pulses where appropriate. Diminished or absent pulses increase the likelihood of PAD, but normal pulses do not exclude the diagnosis.

It is also important to consider other causes of leg pain. Many patients have more than one condition; for example, PAD may coexist with osteoarthritis, neuropathy or spinal stenosis. In people with diabetes, do not assume that foot symptoms are due to neuropathy alone. A new ulcer, unexplained pain, reduced pulses, colour change or reduced walking distance should prompt consideration of arterial disease.

Confirming the diagnosis

NICE recommends measuring the ankle brachial pressure index (ABPI) in people with suspected PAD.⁴ ABPI compares systolic blood pressure at the ankle with systolic blood pressure in the arm. An ABPI of 0.90 or lower is consistent with PAD, although results should always be interpreted alongside the clinical picture.^3,4

In people with diabetes, CKD and advanced age, medial arterial calcification can make arteries difficult to compress. This may produce a falsely normal or elevated ABPI despite significant arterial disease. NICE advises that PAD should not be excluded in people with diabetes on the basis of a normal or raised ABPI alone.⁴ If suspicion remains high, referral for further vascular assessment, including toe pressure or toe brachial index (TBI), may be required.^3–5

When revascularisation is being considered, duplex ultrasound is usually the first-line imaging investigation.⁴ Imaging such as CT/MR angiography may then be used to define arterial anatomy and guide intervention. In primary care, however, the main tasks are to recognise suspected PAD, initiate cardiovascular risk reduction and refer appropriately.

Management

The aims of PAD management are to:

• Improve walking ability and functional capacity;
• Reduce cardiovascular events;
• Prevent progression to limb-threatening disease;
• Maintain independence and quality of life.

Smoking cessation, structured exercise, lipid lowering, blood pressure control, diabetes management and antithrombotic therapy all contribute to improving outcomes.

Smoking, diet and lifestyle

Smoking cessation reduces disease progression and lowers the risk of cardiovascular events, poor revascularisation outcomes, amputation and death.^3–5

Dietary advice should focus on cardiovascular prevention e.g. a Mediterranean-style diet rich in vegetables, fruit, wholegrains, legumes, fish and unsaturated fats. ^3–5 Weight management should be discussed sensitively, particularly where obesity affects mobility or contributes to diabetes, hypertension or dyslipidaemia. Alcohol intake should remain within recommended limits.

Lifestyle advice should not be framed as optional, It is part of treatment. The challenge for many patients is sustaining behaviour change over time.

Exercise prescription for claudication

Exercise therapy is a first-line treatment for intermittent claudication and should be offered to all suitable patients.⁴ NICE recommends supervised exercise where available, but remains underused, with limited availability, low referral rates and variable adherence.⁹Exercise improves pain-free walking distance, maximum walking distance, functional status and quality of life.

Patients should aim for at least three sessions per week, each lasting a minimum of 30 minutes, for at least three months. This usually means walking until moderate claudication discomfort develops, resting until symptoms settle, and then repeating the cycle.

This can sound counterintuitive to patients. Many stop walking because they fear that pain means damage is occurring. Explain that claudication during structured exercise reflects reversible exercise-induced ischaemia, rather than tissue injury. Exercise improves endothelial function, skeletal muscle metabolism, oxygen extraction, gait efficiency and collateral vessel development.

Where supervised exercise is unavailable or not feasible, structured home-based or community-based exercise should be offered rather than vague advice to ‘walk more’. If walking is limited by arthritis, frailty, neuropathy or cardiorespiratory disease, consider alternative modalities such as cycling, resistance training or arm-cranking may be considered, ideally with physiotherapy or exercise specialist input. The key principle is to prescribe exercise in a way the patient can actually sustain.

Treating the cardiovascular risk

A diagnosis of PAD should prompt a structured secondary prevention review, including whether smoking has been addressed, lipid and blood pressure targets are being met, whether diabetes and kidney disease are being treated for maximum cardiovascular and renal benefit, and whether the patient is taking appropriate antithrombotic therapy.

High-intensity statin therapy should be prescribed unless contraindicated. NICE recommends lipid-lowering treatment for secondary prevention, aiming for LDL-C of 2.0 mmol/L or less, or non-HDL-C of 2.6 mmol/L or less.¹⁰ The 2024 ESC/EAS guidelines advocate more intensive LDL-C reduction in very-high-risk patients, with an LDL-C target below 1.4 mmol/L and at least a 50% reduction from baseline.¹¹ The aim is to achieve substantial LDL-C lowering.

If LDL-C remains above target despite maximally tolerated statin therapy, treatment should be intensified in line with NICE and local lipid pathways. Ezetimibe is commonly used as first add-on therapy. Other options include bempedoic acid with ezetimibe for selected statin-intolerant patients, inclisiran for eligible secondary prevention patients in primary care, PCSK9 inhibitors via specialist or local pathways, and icosapent ethyl for selected statin-treated patients with raised triglycerides.

Blood pressure should be managed according to current hypertension guidance. NICE recommends a clinic blood pressure (CBPM) target below 140/90 mmHg for adults under 80 years and below 150/90 mmHg for adults aged 80 years and over, with lower home or ambulatory targets (HBPM/ABPM).¹²In patients at very high cardiovascular risk, lower blood pressure targets may be appropriate (e.g. <130/80 mmHg) where tolerated, but decisions should be individualised, particularly in older adults, people with frailty, postural symptoms, multimorbidity or advanced kidney disease.¹³

In patients with diabetes, the aim is not simply to control HbA1c but to optimise overall cardiometabolic risk.¹⁴ Glycaemic targets should be individualised, taking account of age, frailty, comorbidities, hypoglycaemia risk and patient priorities. NICE recommends intensifying therapy if HbA1c rises to 58 mmol/mol or higher, supporting a target of 53 mmol/mol when treatment is intensified.¹⁴

Antiplatelets and rivaroxaban

Antithrombotic therapy is central to secondary prevention in symptomatic PAD. NICE recommends clopidogrel as first-line antiplatelet therapy, with aspirin used where clopidogrel is unsuitable.⁴ Antiplatelet therapy is prescribed to reduce cardiovascular events, not to improve claudication symptoms.

One of the major developments in PAD management has been the introduction of low-dose rivaroxaban plus aspirin, sometimes described as dual-pathway inhibition. The rationale is that thrombosis in atherosclerotic disease involves both platelet activation and thrombin generation. Targeting both pathways can reduce cardiovascular and limb events, although at the cost of increased bleeding risk.^3,5

NICE TA607 recommends rivaroxaban plus aspirin as an option for adults with symptomatic PAD who are at high risk of ischaemic events and not at high risk of bleeding.¹⁵ Initiation is often specialist-led, particularly after revascularisation or in complex patients, but primary care follow-up is important. GPNs should ask about bruising, gastrointestinal bleeding, anaemia symptoms, falls risk, NSAID use and adherence. Medication lists should be checked carefully to avoid unintended combinations of anticoagulants and antiplatelets.

Symptom-relieving drug therapy

Naftidrofuryl oxalate may be considered for intermittent claudication when supervised exercise has not produced sufficient benefit and the patient prefers not to be referred for angioplasty or bypass surgery.^3,4 Progress should be reviewed after 3–6 months, and treatment stopped if there is no symptomatic benefit.^3,4

This is not a substitute for secondary prevention. Patients receiving medication for claudication still require smoking cessation support, exercise therapy, lipid lowering, blood pressure control, diabetes optimisation and antithrombotic therapy where indicated.

What’s new? GLP-1 receptor agonists

The most interesting recent development in PAD pharmacotherapy is the STRIDE trial, which evaluated once-weekly semaglutide in people with type 2 diabetes and symptomatic PAD.⁶ Semaglutide improved maximum walking distance, pain-free walking distance and health-related quality of life compared with placebo.

This does not mean that semaglutide should be prescribed specifically for PAD in people without diabetes, but suggests that cardiometabolic therapies may have functional as well as cardiovascular benefits in selected patients with PAD.

Review and safety-netting

PAD is a chronic condition requiring ongoing review rather than a ‘diagnose and discharge’ approach. Follow-up should focus on three questions:

1. Are symptoms stable?
2. Is cardiovascular risk being reduced?
3. Is there any evidence of limb threat?

At each review, ask whether walking ability has changed. A shorter claudication distance, new limitation in daily activities or avoidance of usual activities may indicate progression. Rest pain, non-healing ulceration, tissue loss or gangrene should prompt urgent assessment.

Medication adherence should be reviewed, particularly antiplatelet or antithrombotic therapy, lipid-lowering treatment, antihypertensive therapy and diabetes medication. Long-term benefit depends on sustained use, so it is important to ask about side effects, concerns and missed doses. In patients with diabetes, reviews should also consider whether current treatment is delivering maximum cardiovascular and renal benefit, not simply whether HbA1c is acceptable.

Foot assessment is particularly important in people with diabetes, neuropathy or previous ulceration. Feet should be inspected for skin breaks, infection, pressure damage, footwear problems, colour change and tissue loss. Patients should know that new wounds, persistent pain, blackened areas or sudden colour or temperature change require prompt medical attention.

PAD can also affect confidence, independence and mental wellbeing. Patients may stop walking, avoid social activities or fear amputation. Asking about daily function and personal goals can make reviews more meaningful.

When to refer

Referral should follow local vascular pathways and be based on symptom severity, diagnostic uncertainty and the presence of limb-threatening features.

Routine referral is appropriate for lifestyle-limiting claudication despite structured exercise and optimal medical therapy, diagnostic uncertainty or consideration of revascularisation. Urgent referral is required for suspected CLTI, including rest pain, non-healing ulceration, tissue loss or gangrene. Acute limb ischaemia is an emergency and requires immediate same-day assessment.

Conclusion

The most important message for primary care is that PAD should prompt action, even when leg symptoms appear mild. A diagnosis of PAD identifies a patient who needs structured exercise support, smoking cessation, intensive cardiovascular risk reduction, appropriate antithrombotic therapy and careful long-term review.

For GPNs, the opportunity lies in the regularity of contact. Asking about walking distance, checking feet, reviewing adherence and recognising deterioration are simple interventions, but they can change the trajectory of the condition. Earlier recognition may help patients remain independent, while systematic secondary prevention can reduce the risk of myocardial infarction, stroke and limb-threatening complications.

PAD care is therefore not confined to vascular clinics. It belongs in diabetes reviews, cardiovascular reviews, smoking cessation consultations, wound care and long-term condition follow-up. By treating PAD as both a limb condition and a cardiovascular risk marker, primary care teams can make a meaningful difference to quality of life, cardiovascular outcomes and limb preservation.

For a more detailed version of this article, which includes further tables and figures, see Peripheral arterial disease: early recognition, cardiovascular risk and improving outcomes.

References

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