Cardiovascular · PANCE / PANRE

Peripheral Arterial Disease (PAD)

Atherosclerotic stenosis of lower extremity arteries — claudication, ABI ≤0.90, optimized with antiplatelet, statin, exercise.

Also known as: PAD, PVD, peripheral arterial disease, claudication, critical limb ischemia

Overview

Atherosclerotic narrowing of the peripheral arteries, most commonly the lower extremities, producing exertional pain (claudication) or, in severe cases, rest pain, tissue loss, and limb-threatening ischemia.

Epidemiology

Affects ~10-15% of adults over 65 in the US. Strongly associated with coronary and cerebrovascular disease; PAD patients have markedly elevated risk of MI and stroke.

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Risk factors

Smoking (single strongest modifiable risk factor)
Diabetes mellitus (4-fold risk)
Hypertension, dyslipidemia
Age >65 (or >50 with risk factors)
Chronic kidney disease
Hyperhomocysteinemia
Family history of atherosclerosis

Pathophysiology

Atherosclerotic plaque progressively narrows lower extremity arteries. With exertion, demand exceeds the stenosis-limited supply, producing ischemic muscle pain that resolves with rest. Critical limb-threatening ischemia (CLTI) occurs when resting perfusion is inadequate to maintain tissue viability — manifesting as rest pain, non-healing ulcers, or gangrene.

Clinical presentation

Symptoms

Intermittent claudication — cramping, aching, or fatigue in calf, thigh, or buttock with exertion, relieved within 10 minutes of rest
Distance to symptom onset reproducible
Rest pain — burning pain in forefoot at night, relieved by hanging foot off bed (gravity-assisted perfusion)
Non-healing ulcers, gangrene, cold extremity
Erectile dysfunction (Leriche syndrome — aortoiliac disease)

Signs / physical exam

Diminished or absent pulses (femoral, popliteal, dorsalis pedis, posterior tibial)
Cool, pale extremity with dependent rubor and elevation pallor
Hair loss, shiny skin, thickened nails, muscle atrophy
Ulcers — typically dry, punched-out, on toes, lateral malleolus, or pressure points (contrast with venous ulcers)
Bruits over femoral or iliac arteries

Differential diagnosis

Spinal stenosis (neurogenic claudication) — Pain worse with standing/lumbar extension, relieved by sitting or leaning forward; no improvement with rest while standing; normal pulses
Venous claudication — Bursting calf pain after walking, relieved by elevation; history of DVT; signs of chronic venous insufficiency
Deep vein thrombosis — Unilateral leg swelling, warmth, tenderness, Homan sign; D-dimer and duplex US
Compartment syndrome — Pain out of proportion, paresthesia, pallor, paralysis after trauma or exertion (chronic exertional compartment syndrome)
Lumbar radiculopathy — Dermatomal pain, positive straight leg raise, neurologic deficit
Popliteal artery entrapment — Young athlete with calf claudication; pulses disappear with plantar flexion; MRA diagnostic

Diagnostic workup

Diagnostic criteria

ABI ≤0.90 at rest is diagnostic of PAD. ABI ≤0.40 indicates severe PAD. Critical limb-threatening ischemia: rest pain >2 weeks, non-healing wound, or gangrene with abnormal hemodynamics (ankle pressure <50 mmHg or toe pressure <30 mmHg).

Labs

Fasting lipid panel, A1c, BMP (renal function), CBC
Smoking history quantification
hsCRP if borderline risk decisions

Imaging

Ankle-brachial index (ABI) — initial test; normal 1.00-1.40, borderline 0.91-0.99, abnormal ≤0.90
Toe-brachial index (TBI) if ABI >1.40 (non-compressible vessels — diabetes, CKD)
Exercise ABI if resting ABI normal but clinical suspicion high — postexercise drop >20% diagnostic
Duplex ultrasound to localize lesions
CT angiography or MR angiography for anatomic mapping before intervention
Catheter angiography — gold standard, usually combined with intervention

Diagnostic algorithm

ABI value	Interpretation
≥1.40	Non-compressible (calcified) vessels — use TBI
1.00-1.40	Normal
0.91-0.99	Borderline
0.71-0.90	Mild PAD
0.41-0.70	Moderate PAD
≤0.40	Severe PAD; consider critical limb-threatening ischemia

Ankle-brachial index interpretation for peripheral arterial disease.

Treatment

First-line

SMOKING CESSATION — single most important intervention; nicotine replacement, varenicline, bupropion, counseling
Supervised exercise therapy — 30-45 min walking 3+ times per week; superior to most pharmacotherapy for claudication distance
High-intensity statin (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) — LDL goal <70 mg/dL
Antiplatelet therapy: aspirin 81 mg daily OR clopidogrel 75 mg daily
Rivaroxaban 2.5 mg PO BID + aspirin 81 mg daily (COMPASS trial) — for symptomatic PAD to reduce MACE and major adverse limb events
Diabetes control (A1c <7%), blood pressure control (<130/80, ACEi/ARB preferred)
Foot care education for diabetics — daily inspection, properly fitted footwear, podiatry referral

Second-line / adjunct

Cilostazol 100 mg PO BID for refractory claudication — phosphodiesterase 3 inhibitor; CONTRAINDICATED in heart failure
Endovascular revascularization (angioplasty + stent) — for lifestyle-limiting claudication refractory to medical therapy, or CLTI
Surgical bypass (aortobifemoral, fem-pop, fem-tibial) — for long-segment occlusion or failed endovascular therapy
Wound care and limb salvage in CLTI — vascular surgery consultation
Amputation as last resort when revascularization fails or infection threatens life

Complications

Critical limb-threatening ischemia and limb loss
Acute limb ischemia (embolic or thrombotic) — 6 P's: pain, pallor, pulselessness, paresthesia, paralysis, poikilothermia
Myocardial infarction and stroke (PAD doubles risk)
Non-healing infected wounds, sepsis
Restenosis after intervention

PANCE pearls

ABI >1.40 means non-compressible vessels (diabetes, CKD) — get a toe-brachial index instead.
Supervised exercise therapy beats most drugs for claudication distance — prescribe it like a medication.
COMPASS trial: rivaroxaban 2.5 mg BID + aspirin reduces MACE in stable atherosclerosis (CAD or PAD) at the cost of slightly increased bleeding.
Cilostazol is CONTRAINDICATED in heart failure of any severity.
Acute limb ischemia (6 P's) is a vascular emergency — heparin drip and emergent vascular consult; do not wait for imaging.

References

ACC/AHA 2024 PAD — 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease (Gornik et al., Circulation 2024)
COMPASS Trial — Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease (Eikelboom et al., NEJM 2017)
VOYAGER PAD — Rivaroxaban in Peripheral Artery Disease after Revascularization (Bonaca et al., NEJM 2020)
CLEVER Trial — Supervised Exercise Versus Stent Revascularization for Aortoiliac PAD (Murphy et al., Circulation 2012)

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