Overview
Chronic Limb Ischaemia (Peripheral Arterial Disease)
1. Clinical Overview
Summary
Chronic limb ischaemia (CLI) is the end-stage of peripheral arterial disease (PAD), characterised by inadequate arterial perfusion at rest. PAD affects 200 million people worldwide and is a major cause of morbidity, limb loss, and cardiovascular death. The clinical spectrum ranges from asymptomatic disease through intermittent claudication (IC) to critical limb-threatening ischaemia (CLTI) with rest pain, ulceration, or gangrene. ABPI (ankle-brachial pressure index) is the cornerstone diagnostic test. Management combines cardiovascular risk factor modification, supervised exercise therapy, and revascularisation when indicated.
Key Facts
- Prevalence: 10-15% of adults >65 years; 200 million globally
- Mortality: 5-year mortality 20-30% (equivalent to many cancers)
- Claudication: Pain in calf/buttock on walking, relieved by rest
- CLTI (Critical): Rest pain, tissue loss (ulcers, gangrene), ABPI <0.4
- Diagnosis: ABPI <0.9 = PAD; <0.4 = severe/critical
- Treatment: BEST medical therapy + revascularisation if indicated
Clinical Pearls
"PAD = CAD": Patients with PAD have equivalent cardiovascular risk to those with known coronary artery disease. Treat all risk factors aggressively.
"Claudication Distance Matters": Walking distance is the key symptom metric. Supervised exercise can increase walking distance by 50-200%.
"ABPI is Quick and Cheap": Yet massively underutilised. ABPI <0.9 confirms PAD. ABPI >1.3 suggests calcified, incompressible vessels (diabetes, CKD).
"Smoking Cessation is THE Intervention": Single most effective treatment. Reduces amputation risk by 50%.
Why This Matters Clinically
PAD is a marker of systemic atherosclerosis. Most PAD patients die from MI or stroke, not limb complications. Early detection and aggressive cardiovascular risk reduction save lives.
2. Epidemiology
Prevalence
- 10-15% of adults over 65 years
- 200 million people worldwide
- Increases exponentially with age
Demographics
- M > F (2:1)
- Higher in Black and South Asian populations
- Strong correlation with socioeconomic deprivation
Risk Factors
| Modifiable | Non-Modifiable |
|---|---|
| Smoking (OR 4-5x) | Age >0 |
| Diabetes (2-4x) | Male sex |
| Hypertension | Family history |
| Hyperlipidaemia | Ethnicity |
| Chronic kidney disease |
Natural History
- 70-80% of claudicants remain stable or improve
- 10-20% progress to CLTI over 5-10 years
- 1-2% annual amputation rate in claudicants
- 30% 1-year amputation rate in CLTI
3. Pathophysiology
Mechanism
Atherosclerosis of lower limb arteries → Progressive luminal narrowing → Reduced blood flow → Ischaemia
Disease Distribution
| Location | Frequency | Typical Patient |
|---|---|---|
| Aortoiliac | 30% | Younger smokers; Leriche syndrome |
| Femoropopliteal | 50% | Most common; calf claudication |
| Tibial/Below-knee | 20% | Diabetics; poor foot pulses |
Leriche Syndrome
- Aortoiliac occlusion triad:
- Buttock claudication
- Erectile dysfunction
- Absent femoral pulses
Collateral Development
- Chronic stenosis → Collateral vessels develop
- May maintain limb viability despite occlusion
- Explains why some patients tolerate occlusion
Why Claudication Occurs
- At rest: Blood flow adequate through collaterals
- On exercise: Muscle oxygen demand exceeds supply → Ischaemic pain
- Relief with rest: Oxygen debt repaid
4. Clinical Presentation
Fontaine Classification
| Stage | Symptoms |
|---|---|
| I | Asymptomatic |
| IIa | Mild claudication (>00m) |
| IIb | Moderate-severe claudication (<200m) |
| III | Rest pain (critical ischaemia) |
| IV | Tissue loss - ulceration, gangrene |
Intermittent Claudication
| Feature | Description |
|---|---|
| Site | Calf (most common), thigh, buttock |
| Character | Cramping, aching, tired feeling |
| Trigger | Walking (consistent distance) |
| Relief | Rest (typically 2-3 minutes) |
| NOT like | Venous claudication (bursting pain, needs elevation) |
Critical Limb-Threatening Ischaemia (CLTI)
| Feature | Description |
|---|---|
| Rest pain | Nocturnal; forefoot; relieved by dependency |
| Ulceration | Typically toes, heel (pressure points); punched-out |
| Gangrene | Dry (toes) or wet (infected) |
| ABPI | Usually <0.4 |
| Prognosis | 30% amputation, 20% death at 1 year |
Distinguishing PAD from Other Leg Pain
| Condition | Features |
|---|---|
| PAD claudication | Reproducible walking distance, relieved by rest |
| Spinal stenosis | Worse on standing/walking, better sitting/bending |
| Venous claudication | Bursting pain, relieved by elevation |
| Arthritis | Joint stiffness, not distance-related |
5. Clinical Examination
Inspection
- Skin changes: Shiny, hairless, pallid
- Trophic changes: Thickened nails, muscle wasting
- Ulcers: Punched-out, painful (arterial vs venous)
- Gangrene: Dry (mummified) or wet (infected)
Palpation
- Foot temperature: Cool vs warm
- Pulses: Femoral, popliteal, dorsalis pedis, posterior tibial
- Capillary refill: Prolonged >2 seconds
Special Tests
| Test | Method | Interpretation |
|---|---|---|
| Buerger's test | Raise leg 45° → pallor? Lower → rubor? | Positive = severe ischaemia |
| ABPI | Systolic ankle BP ÷ Brachial BP | <0.9 = PAD; <0.4 = severe |
| Toe pressure | Toe cuff measurement | <30 mmHg = critical |
6. Investigations
First-Line
| Test | Purpose | Threshold |
|---|---|---|
| ABPI | Confirm PAD, severity | <0.9 = PAD; <0.4 = severe |
| Duplex ultrasound | Anatomical mapping | Non-invasive, first imaging |
Second-Line (Pre-Intervention)
| Test | Purpose |
|---|---|
| CT angiography | Detailed anatomy for revascularisation planning |
| MR angiography | Alternative (no radiation, avoids contrast in CKD) |
| Digital subtraction angiography | Gold standard (invasive, reserved for intervention) |
Cardiovascular Assessment
| Test | Rationale |
|---|---|
| ECG | Concomitant CAD |
| Echocardiogram | If cardiac symptoms |
| Carotid Duplex | Multi-territory disease |
Blood Tests
- FBC, U&E, HbA1c, Lipid profile
- Renal function (pre-contrast)
7. Management
Risk Factor Modification (ALL PATIENTS)
┌──────────────────────────────────────────────────────────┐
│ BEST MEDICAL THERAPY FOR PAD │
├──────────────────────────────────────────────────────────┤
│ 1. STOP SMOKING │
│ - Single most important intervention │
│ - NRT, varenicline, bupropion, support │
│ │
│ 2. ANTIPLATELET │
│ - Clopidogrel 75mg (preferred) or Aspirin 75mg │
│ - COMPASS: Low-dose rivaroxaban + aspirin in PAD │
│ │
│ 3. STATIN (High-intensity) │
│ - Atorvastatin 80mg │
│ - Target LDL <1.4 mmol/L (very high risk) │
│ │
│ 4. BLOOD PRESSURE CONTROL │
│ - Target <140/90 (or <130/80 if tolerated) │
│ - ACE-I preferred │
│ │
│ 5. DIABETES CONTROL │
│ - HbA1c target individualised │
│ - SGLT2i have vascular benefits │
│ │
│ 6. SUPERVISED EXERCISE THERAPY │
│ - 30-45 min, 3x/week for 12 weeks │
│ - First-line for claudication │
│ - Increases walking distance 50-200% │
└──────────────────────────────────────────────────────────┘
Claudication Management
- Best Medical Therapy (as above)
- Supervised Exercise Programme (first-line)
- Revascularisation if: Lifestyle-limiting, failed exercise, good anatomy
CLTI Management
| Priority | Action |
|---|---|
| 1 | Best Medical Therapy |
| 2 | Revascularisation (endovascular or surgical) |
| 3 | Wound care, offloading |
| 4 | Treat/prevent infection |
| 5 | Amputation if non-salvageable |
Revascularisation Options
| Approach | Examples | Indications |
|---|---|---|
| Endovascular | Angioplasty ± stent | Short stenosis, high surgical risk |
| Surgical bypass | Fem-pop, fem-distal | Long occlusion, good targets, fit patient |
| Hybrid | Combined | Complex disease |
8. Complications
Of PAD
- Acute limb ischaemia (acute-on-chronic)
- Progressive tissue loss
- Amputation (major or minor)
- Chronic pain
- Reduced quality of life
Systemic Complications (Cardiovascular)
- Myocardial infarction (leading cause of death)
- Stroke
- Death (20-30% at 5 years)
Of Interventions
- Restenosis (especially endovascular)
- Graft failure
- Surgical complications (infection, haematoma)
- Contrast nephropathy
9. Prognosis & Outcomes
Claudication Prognosis
- 70-80% remain stable or improve
- 10-20% progress to CLTI over 5-10 years
- 5-year survival: 70%
CLTI Prognosis
- Without revascularisation: 30% amputation at 1 year
- 20% mortality at 1 year
- 50% mortality at 5 years
After Amputation
- 30-day mortality: 5-10%
- Contralateral amputation risk: 10% per year
Prognostic Factors
| Good | Poor |
|---|---|
| Smoking cessation | Continued smoking |
| Good compliance with meds | Diabetes (poor control) |
| Successful revascularisation | Multi-level disease |
| Single-level disease | Renal failure |
10. Evidence & Guidelines
Key Guidelines
- ESC/ESVS Guidelines on Peripheral Arterial Diseases (2024)
- NICE NG168: Peripheral Arterial Disease (2020)
- AHA/ACC Guideline on Lower Extremity PAD (2016)
Key Evidence
COMPASS Trial (2017)
- Rivaroxaban 2.5mg BD + Aspirin vs Aspirin alone
- 24% reduction in MACE in PAD subgroup
- Consider in high-risk PAD
VOYAGER PAD (2020)
- Rivaroxaban 2.5mg BD + Aspirin post-revascularisation
- Reduced limb events and MACE
Supervised Exercise
- Cochrane: Increases pain-free walking by 82m, maximal walking by 109m
- First-line before revascularisation for claudication
11. Patient/Layperson Explanation
What is Peripheral Arterial Disease?
PAD is when the arteries carrying blood to your legs become narrowed or blocked by fatty deposits (atherosclerosis). It's the same process that causes heart attacks and strokes.
What Are the Symptoms?
Claudication (early stage):
- Cramping pain in your calf, thigh, or buttock when walking
- Pain goes away after resting for a few minutes
- You can walk the same distance before pain starts each time
Critical ischaemia (advanced):
- Pain in your foot at rest, especially at night
- Sores on your toes or feet that won't heal
- In severe cases, toes can turn black (gangrene)
How is it Treated?
The most important treatments are:
- Stop smoking - This is the single most effective thing you can do
- Exercise programme - Walking regularly can improve symptoms significantly
- Medications - To thin the blood, lower cholesterol, and control blood pressure
- Surgery or procedures - To open up blocked arteries if needed
Living with PAD
- Keep walking - it's good for you!
- Take your medications regularly
- Check your feet daily for sores or cuts
- See your doctor if symptoms worsen
12. References
Primary Guidelines
- Aboyans V, et al. 2024 ESC/ESVS Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases. Eur Heart J. 2024.
- NICE. Peripheral Arterial Disease: Diagnosis and Management (NG168). 2020. nice.org.uk/guidance/ng168
Key Trials
- Eikelboom JW, et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease (COMPASS). N Engl J Med. 2017;377(14):1319-1330. PMID: 28844192
- Bonaca MP, et al. Rivaroxaban in Peripheral Artery Disease after Revascularization (VOYAGER PAD). N Engl J Med. 2020;382(21):1994-2004. PMID: 32222135