Peripheral arterial disease

• Peripheral arterial disease (PAD) is atherosclerotic narrowing or occlusion of the arteries supplying the lower limbs, from the aortoiliac segment down to the pedal vessels.
• It shares risk factors with coronary and cerebrovascular disease and is itself a marker of widespread atherosclerosis.
• Most patients are asymptomatic or have minor functional limitation; the classic symptom is intermittent claudication, a crampy pain brought on by walking and relieved by rest, within about 10 minutes.
• Examination looks at pulses, skin changes, dependent rubor and capillary refill; the ankle–brachial index (ABI), a ratio of ankle to arm systolic pressure, is the cornerstone test, with an ABI of 0.90 or less diagnostic.
• Treatment targets the leg and the whole vascular system: smoking cessation, high-intensity statin, blood-pressure and glucose control, supervised exercise therapy, single antiplatelet or rivaroxaban 2.5 mg twice daily plus aspirin 81 mg daily in selected patients, cilostazol for claudication, meticulous foot care, and revascularisation for chronic limb-threatening ischaemia and selected cases of claudication.

By the end of this page you should be able to:

1. Define PAD, outline its four clinical subsets, and explain why it matters even when it is silent.
2. Describe the path from endothelial dysfunction to intermittent claudication, rest pain, ulceration and gangrene.
3. Take a vascular history and perform a lower-limb vascular examination, including the ABI and the Buerger test.
4. Interpret an ABI and toe pressure, and choose when duplex ultrasound, computed tomography (CT) or magnetic resonance (MR) angiography, or digital subtraction angiography (DSA) is needed.
5. Grade PAD with the Fontaine, Rutherford and Wound, Ischaemia and foot Infection (WIfI) systems.
6. Recognise acute limb ischaemia (ALI), its six “P”s and its Rutherford stages, and outline emergency management.
7. Build a management plan with medical therapy, exercise, cilostazol, antithrombotic therapy, foot care and revascularisation.
8. Identify the features that separate neurogenic and venous leg pain from vascular claudication.
9. Adapt investigation and treatment to diabetes and low-resource settings.

The 2024 ACC/AHA guideline recognises four clinical subsets, and these frame everything that follows.^[1] Asymptomatic PAD is common (20% to 59% of patients with objectively proven disease report no leg symptoms) and still carries a high rate of major adverse cardiovascular events. Chronic symptomatic PAD includes intermittent claudication and other exertional leg symptoms that limit walking. Chronic limb-threatening ischaemia (CLTI) is chronic (>2 weeks) ischaemic rest pain, non-healing wound or ulcer, or gangrene attributable to proven arterial disease; it replaces the older term “critical limb ischaemia”. Acute limb ischaemia (ALI) is a sudden (≤2 weeks) decrease in arterial perfusion that threatens limb viability, with the classic “six Ps”.

This page covers lower-limb atherosclerotic disease. It does not cover vasculitis, fibromuscular dysplasia, entrapment syndromes, cystic adventitial disease or trauma.^[1] These are excluded because they have different mechanisms and treatments.

Estimates of how common PAD is depend on the population and on whether sensitive or specific measures are used. The 2024 ACC/AHA guideline estimates that 10 to 12 million people in the United States over 40 years of age have PAD and that worldwide at least 113 million and perhaps as many as 236 million people have the disease.^[1] An educational review based on the COMPASS cohort describes lower-extremity PAD as affecting more than 200 million people worldwide.^[5] Population studies find that about 20% of people aged over 60 years have some degree of PAD; estimates rise with age and vary with the population and diagnostic method tested.^[4]

The disease is heavily concentrated where atherosclerosis and its risk factors are common. Among people with diabetes, PAD affects 20% to 28%, and up to 50% of those with diabetic foot disease.^[4] Coronary and carotid disease coexist frequently, so PAD is often one part of polyvascular disease (disease in two or more vascular beds).

A large proportion of patients are asymptomatic or have only functional impairment, depending on how they are assessed.^[1] Yet asymptomatic patients have worse cardiovascular outcomes and a faster decline in walking performance than people with a normal ABI.^[1]

PAD is atherosclerosis of the limb arteries, driven by the same process that affects the coronaries and carotids. The atherosclerotic process is covered in general under dyslipidaemia and essential hypertension; this page limits itself to PAD-specific points. Risk factors can be separated into non-modifiable (age, male sex, ethnicity, family history) and modifiable ones. The modifiable risk factors that matter most are smoking, diabetes mellitus, systemic hypertension, dyslipidaemia, chronic kidney disease and physical inactivity.^[1][4]

• Smoking is the single strongest risk factor for PAD and is especially powerful for disease below the knee. Stopping smoking is the most cost-effective intervention in the whole topic.
• Diabetes accelerates disease, particularly infrapopliteal disease, and worsens outcomes after revascularisation.
• Hypertension and dyslipidaemia are shared with coronary and carotid disease.
• Age of 65 years or older and 50 to 64 years with risk factors for atherosclerosis or a family history of PAD, as well as the presence of diabetes, CKD, known coronary or cerebrovascular disease, or a foot ulcer place a person in the group for whom assessment is recommended.^[1]
• Renal impairment (eGFR <60 mL/min) is a high-risk comorbidity: in the COMPASS analysis patients with kidney insufficiency had a 14.1% 30-month risk of major adverse cardiovascular or limb events.^[5]

In practice PAD and coronary or carotid disease cluster. Finding one should prompt a search for the others.

Atheroma forms in the intima of medium and large arteries. Endothelial dysfunction allows lipoproteins in, macrophages foam cells form, and a fibrous cap develops over a lipid core. As the plaque grows, the lumen narrows, first reducing flow reserve without symptoms, then limiting resting flow. Collateral vessels develop, but when narrowing is severe they cannot compensate for sudden demand.

The symptoms follow the physiology:

1. Intermittent claudication (pain with exertion, relief with rest). Walking raises oxygen demand in the calf or thigh muscles. A stenosis prevents the rise in flow needed, so muscle metabolism shifts to glycolysis and ischaemic metabolites generate pain. Stopping walking removes the demand and the pain fades, usually within about 10 minutes.^[1]
2. Ischaemic rest pain appears when perfusion at rest falls below what skin and nerve demand, often in the forefoot, and wakes the patient at night. Gravity helps, so the pain is eased by hanging the foot out of bed (dependency).
3. Tissue loss and gangrene follow chronically low distal perfusion combined with minor trauma and impaired healing: non-healing ulcer and then dry (or wet, infected) gangrene.
4. Acute limb ischaemia occurs when thrombus forms on a plaque or an embolus lodges (often from the heart, especially in atrial fibrillation), stopping flow suddenly. With no time to recruit collaterals, all metabolically active tissues — muscle and nerve — are at risk within hours.

Diabetes adds diffuse distal disease and medial arterial calcification, which stiffens the artery wall and makes some tests less reliable, but the fundamental problem remains reduced arterial perfusion.

A careful history asks about walking distance, where the pain starts, how it is relieved, what limits it, and whether rest pain or wounds are present. Many patients “walk through” severe PAD without pain by modifying their lifestyle, so questions about function are as important as questions about pain.^[1]

• Intermittent claudication: fatigue, cramping, aching pain or other discomfort of vascular origin in the buttocks, thigh, calf or foot, consistently brought on by walking, not starting at rest, and usually relieved within about 10 minutes of rest.^[1] Tingling, numbness, burning or “dead-leg” feelings also occur.
• Atypical exertional leg symptoms are common and still limit function. They may not be typical claudication because they may start at rest or take longer than 10 minutes to resolve.
• Ischaemic rest pain: aching or burning in the forefoot, worse at night and with leg elevation, better with the foot dangling over the edge of the bed. It is a marker of CLTI.
• Wounds and gangrene: non-healing ulcers of the toes, heels or pressure points, and dry or wet gangrene.

ALI develops over minutes to days: new or worsening claudication, severe rest pain, paraesthesia, muscle weakness, paralysis and even gangrene. The classic mnemonic is the six “P”s.^[1][6]

Embolic occlusions have a sudden, clearly timed onset with severe symptoms (there are no collaterals); thrombotic occlusions on chronic plaques have an insidious onset, patients can have prior claudication, and the limb may be less obviously ischaemic because collaterals exist.^[6]

See cardiac physical examination for the general cardiovascular approach. PAD is a systemic disease: inspect the whole vascular tree, the abdomen for aneurysm, and the feet.

• Pulses: palpate femoral, popliteal, posterior tibial and dorsalis pedis, comparing both sides. A cool, pale limb with absent pulses is the hallmark. Document the pulse (present, diminished, absent); if doubt exists, use a continuous-wave Doppler probe and listen for triphasic flow (normal), dampened signals or none.
• Skin: dry, shiny skin, hair loss on the dorsum of the foot, thickened or dystrophic nails, muscle wasting and a cold foot.
• Capillary refill is delayed beyond the usual brisk return when perfusion is impaired.
• Dependent rubor and elevation pallor: the foot is red and warm when down and pale when raised to 90°. This is a simple, useful bedside test.
• Buerger test: with the patient lying, raise both legs and look for pallor, then let them hang and watch for reactive hyperaemia. Slow colour return supports arterial disease rather than venous insufficiency; press over a toe and note how long colour takes to return.
• Bruit: listen over the aorta, iliac and femoral arteries.
• Wounds and gangrene: note location, depth and infection.
• Neurological status: light touch, pinprick, proprioception and motor power; these are vital in ALI.

Table 1. Fontaine and Rutherford classifications of lower-limb ischaemia (from a 2024 review of PAD in diabetes^[4])

Table 2. Rutherford stages of acute limb ischaemia^[6]

Staging matters because it drives the urgency and choice of treatment: stage I to IIa can be imaged electively, IIb needs immediate revascularisation, and III is usually managed with amputation and (where appropriate) palliation rather than heroic revascularisation.

The table separates vascular claudication from its two common mimics: neurogenic claudication (lumbar spinal stenosis) and venous disease.

Table 3. Vascular claudication versus neurogenic claudication and venous pain

Other causes to consider: osteoarthritis or musculoskeletal pain (joint-centred, pain with specific movements, normal pulses), Baker's cyst, chronic compartment syndrome in athletes, arthritis and gout, Morton's neuroma and peripheral neuropathy (burning, paraesthesia without exertional relationship).

The ABI is the ratio of the highest ankle systolic pressure to the higher of the two brachial systolic pressures. It is quick, cheap and reproducible, and remains the cornerstone of PAD diagnosis.^[1][2]

Measurement (NICE CG147^[3]): the patient lies resting and supine. Measure systolic pressure with an appropriately sized cuff in both arms and over the posterior tibial, dorsalis pedis and, where possible, peroneal arteries, using a hand-held Doppler probe, and calculate each leg's index by dividing the highest ankle pressure by the highest arm pressure. Document the Doppler signal quality.

Interpretation (ACC 2024^[1] and the diabetic PAD review^[4]):

Note: the two opened ABI sources define the lower end of the normal band differently - the 2024 ACC/AHA normal band is 1.00–1.40 (0.91–0.99 borderline), whereas the 2024 diabetic PAD review uses normal values of >0.90 to <1.30–1.40 (counting 0.91–0.99 as borderline-positive). The guidelines differ in definition, and both conventions remain in use.^[1][4]

The ABI has a sensitivity of 68% to 84% and a specificity of 84% to 99% for angiographically confirmed disease in non-diabetic patients.^[4] In symptomatic patients the sensitivity falls to 69% to 79% but the test remains highly specific.^[1]

Important limitation: in diabetes and chronic kidney disease, medial arterial calcification can make arteries non-compressible, giving a falsely high ABI (often >1.40) despite severe disease. In these patients ABI alone does not exclude PAD, and do not exclude PAD in diabetes on the basis of a normal or raised ABI alone.^[3][4]

Digital arteries are much less affected by calcification, so they are the next tests when the ABI is unreliable or the limb is threatened.

• Toe pressure ≤50 mmHg indicates reduced perfusion; ≤30 mmHg indicates CLTI.^[4]
• Toe–brachial index (TBI) ≤0.70 is abnormal and supports PAD in patients with a non-compressible ABI (ABI >1.40).^[4]
• Transcutaneous oxygen pressure (TcPO₂) under 30 mmHg indicates critical skin perfusion and predicts poor wound healing; normal values at the skin are 60 to 70 mmHg.^[4]

Non-invasive anatomy is obtained with duplex ultrasound (first-line where revascularisation is being considered, combining greyscale, colour Doppler and pulsed-wave Doppler to locate stenosis and measure peak systolic velocities), with contrast-enhanced MR angiography offered where further imaging is needed, and CT angiography where MR is contraindicated or not tolerated.^[3]

Digital subtraction angiography (DSA) remains the gold standard for mapping the arterial tree and is both diagnostic and interventional; it is used before revascularisation and where non-invasive imaging is equivocal or distal disease must be defined.^[4][6]

Exercise treadmill testing with ABI (ABI before and after a standardised walk) is useful when symptoms are present but the resting ABI is normal or borderline (0.91–1.40), and to document functional limitation. Segmental pressures, PVR and continuous-wave Doppler waveforms help delineate the level of disease.

PAD is diagnosed clinically and confirmed physiologically: a resting ABI of 0.90 or less (or a TBI ≤0.70 in diabetes/non-compressible vessels), in a patient whose history or examination suggests PAD. Confirmatory imaging is added when the diagnosis is in doubt or revascularisation is planned.^[1][4]

Severity for prognosis and treatment is staged with Fontaine/Rutherford (Tables 1 and 2) and, for CLTI, the WIfI system, which scores wound extent, degree of ischaemia and severity of infection to estimate the risk of major amputation and of benefit from revascularisation.^[1][4]

Management runs on two parallel tracks at every stage: (1) whole-patient cardiovascular risk reduction, because most patients with PAD die of a heart attack or stroke rather than losing a limb; and (2) limb-directed therapy, driven by the patient's symptoms and classification.

• Smoking cessation is the highest-value intervention; it slows progression of PAD and improves claudication distance. Use combined pharmacological and behavioural programmes.
• Antiplatelet therapy: in general a single antiplatelet is used. NICE CG147^[3] recommends clopidogrel as an option for preventing occlusive vascular events in PAD, and aspirin is the standard alternative. Rivaroxaban plus aspirin is dealt with separately below.
• Blood pressure: treat systemic hypertension; the 2024 ESC guidance lists antihypertensive treatment for PAD.^[2] ACE inhibitors are a good choice; set the blood-pressure target according to general hypertension guidance.
• Diabetes: tight glycaemic control reduces microvascular complications; set the HbA1c target individually, particularly where hypoglycaemia must be avoided.
• Lipid lowering: prescribe a high-intensity statin for every patient with PAD. Continue even when LDL (low-density lipoprotein) cholesterol appears at target, because of statins' non-lipid effects, and add ezetimibe and then a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor if targets are not met. (Specific doses and targets vary by lipid guideline and formulary.)
• Vaccination (yearly influenza, COVID-19 as recommended) and rheological review (optimise anaemia, heart failure) are easy wins.

Structured exercise is core to PAD care and improves walking performance, functional status and quality of life, in symptomatic patients and after revascularisation.^[1][2]

NICE CG147 recommends a supervised exercise programme for everyone with intermittent claudication, at 2 hours of supervised exercise per week for 3 months, encouraging exercise to the point of maximal pain.^[3] A standard SET (supervised exercise therapy) session is treadmill-based interval walking into moderate-to-severe claudication with rest periods, supervised by a clinical exercise physiologist or nurse. Community-based (home-based) structured programmes with behavioural change are an acceptable alternative where supervised programmes are not available.^[1]

Cilostazol is a phosphodiesterase III inhibitor that inhibits platelet aggregation and dilates arterioles; it is the only pharmacological treatment with consistent evidence of improved walking distance in claudication.

• Dose: 100 mg twice daily, taken at least half an hour before or two hours after food (bioavailability rises with a high-fat meal).^[7]
• Reduce to 50 mg twice daily with CYP3A4 or CYP2C19 inhibitors (for example diltiazem, erythromycin, omeprazole).^[7]
• Continuation: benefit may appear at 2 to 4 weeks but up to 12 weeks can be needed; stop if symptoms are unimproved after 3 months.^[7]
• It is used for patients with Fontaine stage II (intermittent claudication without rest pain or tissue loss) after lifestyle modification and other treatment have been tried; it is contraindicated in heart failure of any severity, and it should be avoided in patients with haemostatic disorders or active pathologic bleeding.^[7]

Note that NICE TA223 does not recommend cilostazol in its routine guidance stream, while international guidance (SVS) does; local practice and licensing differ, so follow your local guideline.

The most important antithrombotic finding in PAD of the last decade is low-dose rivaroxaban 2.5 mg twice daily added to aspirin 81 mg daily. The 2024 ACC/AHA guideline states this combination is effective to prevent major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with PAD who are not at increased risk of bleeding.^[1] The 2024 ESC guidance recommends single antiplatelet (aspirin or clopidogrel) for symptomatic PAD as a class I/A recommendation, and dual antithrombotic (low-dose rivaroxaban plus aspirin) as class IIa/A for patients with PAD at high ischaemic risk and low bleeding risk.^[2] The two guidelines genuinely differ in strength (AHA says “effective”; ESC labels it IIa/A), and bleeding and risk stratify the decision.

COMPASS enrolled 27 395 patients with coronary or peripheral artery disease. In the symptomatic lower-extremity PAD subgroup (n = 4129), rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily, compared with aspirin alone, produced a 26% relative reduction in MACE (hazard ratio 0.74), a 45% reduction in MALE including major amputation (HR 0.55), and a 29% reduction in the composite of MACE or MALE (HR 0.71), at the cost of more major bleeding (HR 1.69). Fatal or critical organ bleeding was not significantly increased. The 30-month incidence of MACE or MALE was 22.6% after prior amputation, 17.6% with Fontaine III/IV symptoms and 11.8% after prior revascularisation; high-risk comorbidities followed (polyvascular disease 12.8%, diabetes 13.4%, heart failure 13.5%, kidney insufficiency 14.1%). Those at high risk had an estimated 4.2% absolute risk reduction at 30 months for MACE or MALE, with a net clinical benefit estimated at 3.2%.^[5]

VOYAGER PAD tested the same combination soon after lower-extremity revascularisation and showed a 15% reduction in the composite of myocardial infarction, ischaemic stroke, cardiovascular death, acute limb ischaemia or major amputation, with more major bleeding on the ISTH definition but no excess of severe bleeding.^[5] Together, the two trials cover chronic stable disease (COMPASS) and the post-revascularisation window (VOYAGER).

Practical take-home: combine rivaroxaban 2.5 mg twice daily with low-dose aspirin 81/100 mg daily in patients with PAD and high ischaemic risk who are not at high bleeding risk; reassess bleeding risk, renal function and drug interactions, and stop or avoid if contraindicated. Rivaroxaban is not a substitute for antiplatelet; single antiplatelet (aspirin or clopidogrel) is the alternative, especially where bleeding risk is high or cost is an issue.

Revascularisation aims to save the limb in CLTI and to improve walking distance and quality of life in selected patients with claudication that persists despite risk-factor control and supervised exercise.^[1]

• Decision by a multidisciplinary vascular team (vascular surgery, interventional radiology, vascular medicine, podiatry and diabetology) before treatment decisions in CLTI.^[3]
• Endovascular first (angioplasty, with or without stenting or atherectomy) is preferred in many patients with CLTI and is the main strategy for aortoiliac and femoropopliteal disease, particularly where surgical risk is high. Autologous vein is preferred for infrageniculate bypass.
• Surgical bypass with an autologous vein remains the most durable option for extensive or infrapopliteal disease, and is favoured by the evidence where long-term patency matters; prosthetic grafts are used where no vein is available.
• Hybrid procedures combine both in a single setting.
• The WIfI classification (wound, ischaemia, foot infection) stratifies risk of major amputation and helps select candidates for revascularisation; rest pain itself without tissue loss constitutes CLTI but revascularisation is usually reserved for those whose symptoms are limiting or the limb is threatened.
• Revascularise after imaging (duplex first, then CTA/MRA, DSA when needed) and only after GDMT and exercise have been offered.

ALI is a surgical/vascular emergency; the limb can be irreversibly damaged within hours.

1. Anticoagulate immediately with unfractionated heparin (UFH) to halt thrombus propagation and preserve microcirculation; give intravenous analgesia; correct fluid, electrolyte and acid-base abnormalities; check clotting and renal function; and get a chest radiograph and electrocardiogram to search for an embolic source such as atrial fibrillation.^[6]
2. Assess viability with the Rutherford stages (Table 2).^[1][6]
3. Imaging if time allows: colour duplex ultrasound is first choice; CTA/MRA are reserved for non-immediately threatened limbs because ALI patients tolerate long imaging sessions poorly.^[6]
4. Revascularise according to the stage and cause:
   • Stage I–IIa (viable or marginally threatened): endovascular preferred — catheter-directed thrombolysis or pharmacomechanical/aspiration thrombectomy (thromboaspiration, mechanical thrombectomy). Catheter-directed thrombolysis achieves complete or partial resolution in 75–92% of occluded native vessels, stents or grafts, but is usually not used in stage IIb. Thrombolytic agents (streptokinase, urokinase, alteplase) require a heparin infusion and ICU monitoring. Drug-dose tables and absolute/relative contraindications must be checked against the local protocol before use.^[6]
   • Stage IIb (immediately threatened) and embolic occlusion with an absent femoral pulse: surgical — balloon-catheter (Fogarty) embolectomy or bypass, with on-table angiography.^[6]
   • Stage III (irreversible): amputation (or, in the appropriate patient, palliative care) rather than revascularisation for a non-viable limb.
   • Open and endovascular approaches have similar short-term and 12-month mortality, amputation and recurrent ischaemia rates in meta-analysis, so both remain valid; the choice rests on anatomy, team skill and expediency.^[6]
5. After revascularisation: watch for reperfusion injury and compartment syndrome (anterior compartment pressure >30 mmHg is diagnostic; treat with fasciotomy). Monitor the kidney, toe and sensory/motor function. Long-term anticoagulation for embolic/atrial-fibrillation cases; antiplatelet plus statin for atherosclerotic thrombosis; dual antiplatelet for at least a month after stent.^[6]

Foot care is crucial across all subsets, from prevention to advanced wound management.^[1] Educate every patient with PAD (with diabetes in particular) on daily foot inspection, keeping the foot clean and dry, avoiding sharp self-treatment of nails or callus, not walking barefoot, and wearing well-fitting footwear. Arrange podiatry or wound-care specialist assessment for any ulcer or gangrene; good shoes, offloading and access to wound-healing expertise all reduce amputation.^[1]

• Acute limb ischaemia and major amputation (about 30% 1-year amputation rate for CLTI in historical series; more recent trials report lower figures).^[1]
• 30-day mortality after ALI of 10% to 15%, despite modern treatment, and a substantial rate of in-hospital myocardial infarction, heart failure and renal dysfunction.^[6]
• CLTI carries historically estimated 1-year mortality of 25% to 35% and amputation up to 30%.^[1]
• Major adverse cardiovascular events (myocardial infarction, stroke, cardiovascular death): the risk is 3- to 6-fold that of matched people without PAD.
• Revascularisation failure, graft thrombosis and restenosis.
• Reperfusion injury and compartment syndrome after revascularisation for advanced ischaemia.
• Infection of ulcers, progressing to wet gangrene and sepsis.
• Drug-specific complications: cilostazol is contraindicated in heart failure; rivaroxaban/aspirin increases major bleeding (mostly gastrointestinal).

PAD is a marker of systemic atherosclerosis: people with PAD die more often from cardiovascular causes than non-PAD patients. The limb outlook depends on the subset:

• Most patients with intermittent claudication remain stable for years.
• Around 11% to 20% of patients with known PAD develop CLTI, and the incidence of ALI in a contemporary symptomatic PAD cohort was 1.7% (0.8 events per 100 patient-years).^[1]
• Once CLTI or ALI develops, both limb loss and total mortality rise sharply.
• Polyvascular disease (PAD plus coronary or carotid disease) worsens prognosis (see heart failure for the general management of left-ventricular dysfunction).

Prevention is risk-factor control and antiplatelet/statin therapy, as above. Screening with the resting ABI is reasonable in patients at increased risk of PAD (age ≥65, 50–64 with risk factors or family history, diabetes, CKD, established atherosclerotic disease, foot ulcer) and not recommended in low-risk asymptomatic people.^[1] Where resources permit, early detection in diabetes allows risk reduction before ulceration develops.

• Diabetes: disease is more distal, medial calcification makes ABI falsely high, classic symptoms are masked by neuropathy and sedentary lifestyle. Use toe pressures, TBI and Doppler waveforms, and suspect PAD in any diabetic with a non-healing foot wound. Screen early and aggressively, because diabetic patients with PAD have roughly double the amputation and mortality.^[4]
• Older adults: disease is common and multi-system; weigh benefit of intervention against frailty and life expectancy; ensure comprehensive geriatric assessment.
• Atrial fibrillation: an important embolic source for ALI (see atrial fibrillation and flutter); anticoagulation for stroke prevention incidentally reduces embolic ALI.
• Heart failure: cilostazol is contraindicated; revascularisation risk rises; involve the multidisciplinary team.
• Pregnancy: revascularisation decisions require specialist teams; conservative medical risk control is preferred unless limb is threatened. (No specific pregnancy data opened; manage by specialist.)

• Clinical diagnosis first: absent pulses, dependent rubor, elevation pallor, skin and nail changes, and cold feet strongly suggest PAD; combine with a handheld Doppler where possible.
• Manual ABI with a simple sphygmomanometer and Doppler probe costs little and is highly informative even in district hospitals; do not rely on automated cuffs in calcified vessels.
• Toe pressures are cheap and especially valuable in diabetic feet.
• Exercise therapy is free: simplest recommendation is supervised or structured walking to the point of pain, even without a formal rehabilitation unit; group-based programmes in community settings work.
• Risk-factor control (smoking cessation, statin, ACE inhibitor, antiplatelet or rivaroxaban/aspirin if available, foot care) does most of the benefit and needs no specialist centre.
• Refer early when there is CLTI or any ALI: revascularisation and amputation require a surgical centre, and delayed referral costs limbs.
• Amputation is a last resort after vascular assessment: a preventable amputation is a failure of care, not a solution.

• PAD is atherosclerotic lower-limb arterial disease and a marker of systemic atherosclerosis; it is often silent but still carries high cardiovascular risk.
• The four clinical subsets are asymptomatic, chronic symptomatic (claudication), CLTI and ALI, and patients move between them.
• Classic claudication is exertional cramp relieved by rest within about 10 minutes; neurogenic claudication worsens with standing and improves with flexion or cycling.
• The six Ps of ALI are pain, pallor, pulselessness, poikilothermia, paraesthesia and paralysis; stages I to III decide urgency and revascularisation versus amputation.
• An ABI of 0.90 or less is diagnostic of PAD; in diabetes or CKD a non-compressible ABI (>1.40) demands toe pressures and Doppler.
• Toe pressure ≤50 mmHg indicates reduced perfusion; ≤30 mmHg, CLTI. TBI ≤0.70 is abnormal. TcPO₂ under 30 mmHg indicates critical skin perfusion.
• Always screen for, and treat, polyvascular disease (coronary, carotid, aortic) and its risk factors.
• Single antiplatelet is standard; rivaroxaban 2.5 mg twice daily plus low-dose aspirin is effective in PAD at high ischaemic and low bleeding risk; ESC labels it IIa/A, AHA calls it effective — guidelines genuinely differ in phrasing.
• High-intensity statin, blood-pressure and glucose control, smoking cessation and foot care benefit the leg and the heart.
• Supervised exercise therapy (NICE: 2 hours per week for 3 months, to maximal pain) improves walking.
• Cilostazol 100 mg twice daily (reduced to 50 mg twice daily with interacting drugs) helps claudication but is contraindicated in heart failure; stop if no benefit at 3 months.
• Revascularise to save the limb in CLTI using a multidisciplinary team; endovascular for stage I–IIa ALI, surgical embolectomy for IIb embolism; anticoagulate ALI immediately with UFH.
• In low-resource settings, clinical examination and a manual ABI are the best tools; refer CLTI and ALI promptly.

• Cardiac physical examination
• ECG interpretation
• Atrial fibrillation and flutter
• Heart failure
• Approach to tachyarrhythmias
• Ventricular arrhythmias
• Bradyarrhythmias and AV block
• Supraventricular tachycardias

The references are listed in the front matter. All facts, doses, thresholds and classifications above are as reported in those sources; where guidelines differ this is stated in the text.