Intermittent Claudication

Exertional leg muscle pain or cramping, reproducible at a consistent walking distance and relieved within a few minutes of rest, caused by peripheral artery disease. About 3 to 10% of adults have peripheral artery disease (15 to 20% over age 70), and about a third to a half of those have claudication.

• Site of pain indicates the level: calf (femoropopliteal disease), thigh and buttock (aortoiliac disease, with erectile dysfunction in Leriche syndrome), foot or buttock. Risk factors: smoking, diabetes, hypertension, hyperlipidaemia, chronic kidney disease, age and family history.
• Prognosis: the limb outlook is benign (about 1 to 3% progress to chronic limb threatening ischaemia per year; major amputation less than 2% at 5 years). The cardiovascular outlook is poor: about 20% have a myocardial infarction, stroke or vascular death at 5 years, and all-cause mortality is about 2 to 3 times that of age matched peers.

• Reproducible cramping, aching or tiredness in a muscle group after a fixed distance, which resolves within 1 to 5 minutes of standing still (no need to sit or bend). Pain does not occur at rest.
• Signs: reduced or absent femoral, popliteal or pedal pulses, femoral or abdominal bruits, cool feet, hair loss, shiny skin, and a ratio drop on exercise.
• Differential diagnosis: neurogenic claudication from lumbar spinal stenosis (relief on sitting or leaning forward, pain on standing), chronic venous claudication (bursting pain, relieved by elevation), hip or knee arthritis, chronic exertional compartment syndrome, popliteal artery entrapment (young athletes), Baker cyst, peripheral neuropathy, deep vein thrombosis, and statin related myopathy.
• Complications: progression to chronic limb threatening ischaemia, acute limb ischaemia from thrombosis, myocardial infarction, stroke, aortic aneurysm, depression, and reduced mobility.

• Resting ankle brachial pressure index: less than 0.90 is abnormal; 0.91 to 1.30 is normal; greater than 1.30 suggests non-compressible calcified vessels (use toe brachial index and toe pressure). With a normal resting index but typical symptoms, repeat after exercise (a fall in ankle pressure of more than 30 mmHg, or an index fall greater than 20%, confirms disease).
• Treadmill test (3.2 km/h at 10 to 12% incline) to measure claudication distance and maximal walking distance.
• Duplex ultrasonography, then CT angiography or MR angiography only if revascularisation is being considered.
• Blood tests: lipids, HbA1c, creatinine, full blood count. ECG, and screening for carotid, coronary and abdominal aortic disease (ultrasonography for abdominal aorta in men over 65).

• Every patient needs cardiovascular risk reduction; most improve with exercise alone.
• Exercise and lifestyle:
  • Supervised exercise programme: 30 to 60 minutes, 3 sessions weekly for at least 12 weeks, walking to moderate-to-maximal claudication pain, resting, then repeating. Walking distance improves by about 50 to 200%.
  • Without supervision: walking for 30 to 45 minutes at least 3 to 5 times weekly to near maximal pain.
  • Weight loss, Mediterranean style diet, and daily foot inspection (especially in diabetes).
  • Smoking cessation: nicotine patch 21 mg/24 h (14 mg for 10 or fewer cigarettes a day), varenicline 0.5 mg daily for 3 days, 0.5 mg twice daily for 4 days, then 1 mg twice daily for 12 weeks.
• Medical therapy:
  • Aspirin 75 to 100 mg daily or clopidogrel 75 mg daily. For symptomatic disease with low bleeding risk, rivaroxaban 2.5 mg twice daily with aspirin 100 mg daily lowers limb and cardiovascular events.
  • Atorvastatin 40 to 80 mg daily (target LDL cholesterol less than 1.4 mmol/L, with at least 50% reduction); add ezetimibe 10 mg daily if needed.
  • Blood pressure target less than 140/90 mmHg (less than 130/80 mmHg in diabetes or kidney disease) with ramipril 2.5 to 10 mg daily; beta blockers are safe if indicated.
  • HbA1c about 53 mmol/mol (7%) in diabetes; SGLT2 inhibitors or GLP-1 receptor agonists as indicated.
  • Cilostazol 100 mg twice daily, taken 30 minutes before or 2 hours after meals, if exercise is insufficient; assess the response after 12 weeks and stop if there is no improvement. Contraindications: heart failure of any severity, history of ventricular arrhythmia, unstable angina, and bleeding disorders. Reduce to 50 mg twice daily with strong CYP3A4 or CYP2C19 inhibitors (diltiazem, erythromycin, omeprazole, ketoconazole). Side effects: headache, diarrhoea, palpitations, dizziness.
  • Naftidrofuryl 200 mg three times daily for 3 to 6 months where available. Pentoxifylline offers little benefit.
• Revascularisation for lifestyle limiting claudication after at least 3 months of exercise and medical therapy, when anatomy is suitable and the patient accepts the risk:
  • Endovascular treatment (angioplasty with or without stent or drug coated balloon) for aortoiliac and short femoropopliteal lesions.
  • Bypass surgery (aortobifemoral or femoropopliteal with vein) for extensive aortoiliac disease or long femoropopliteal occlusions in fit patients; perioperative mortality about 2 to 4% (higher for aortic bypass).
  • During endovascular treatment give unfractionated heparin 70 to 100 units/kg IV; after treatment give aspirin 75 to 100 mg daily with clopidogrel 75 mg daily for 1 to 3 months, then single antiplatelet therapy.
• Special groups:
  • Diabetes: strict foot care, daily inspection, and podiatry review; disease is more distal and symptoms can be masked by neuropathy.
  • Chronic kidney disease: use toe pressures, avoid contrast when possible, and control blood pressure and lipids intensively.
  • Elderly: tailor exercise to ability; avoid hypotension from antihypertensive therapy.
  • Young patients: consider popliteal entrapment, adventitial cystic disease and thromboangiitis obliterans; stop all tobacco.
  • Pregnancy: rare; avoid statins, ACE inhibitors and cilostazol.
• Red flags: rest pain, ulcer or gangrene, sudden worsening or a cold foot, walking distance falling rapidly, absent pulses after previously present pulses.
• Follow up: review every 3 to 6 months initially, then yearly, with ankle brachial pressure index, walking distance, blood pressure, lipids, HbA1c and smoking status; repeat imaging only for planned revascularisation or progression.