Peripheral arterial disease (PAD) is a condition characterized by the atherosclerotic narrowing of peripheral arteries, most commonly of the lower extremities. Lower extremity PAD may be asymptomatic or manifest with intermittent claudication, critical limb ischemia (CLI), or acute limb ischemia (ALI), which is a surgical emergency that is described in a separate article. In the absence of acute ischemia, the first-line diagnostic test for PAD is the ankle-brachial index (ABI). Imaging, preferably via MR angiography, is indicated if revascularization is planned or if the diagnosis remains uncertain. Structured exercise therapy and modification of cardiovascular risk factors may improve intermittent claudication significantly; cilostazol, a vasodilator, may be considered for symptomatic relief. Revascularization is indicated in patients with limb ischemia and those with life-limiting claudication despite exercise therapy. Additionally, should be initiated in all patients to minimize the risk of atherosclerotic cardiovascular disease.
- Prevalence: 8.5 million in the US
- Peak incidence: 60–80 years of age
- Sex: ♂ = ♀ 
Peripheral arterial disease is equally common in women and men. 
Epidemiological data refers to the US, unless otherwise specified.
- Risk factors for PAD: The following patient groups are at increased risk of PAD.
Up to 20–50% of patients with PAD are asymptomatic.
- Seen in approx. 10–35% of patients
Pain, cramps, or paresthesia distal to arterial occlusion
- Femoropopliteal disease (most common): typically causes calf claudication
- Aortoiliac disease (Leriche syndrome)
- Tibiofibular disease: typically causes foot claudication
- Worsens upon exertion ,
- Completely relieved by rest or lowering affected limbs
- Reproducible on asking the patient to walk the same distance at which symptoms typically occur
- Typically occurs first in the toes and forefoot
- Worsens with reclining (e.g., while sleeping)
- Improves on hanging feet off the bed or on standing
Critical limb ischemia (CLI) 
- Indicative of limb-threatening arterial occlusion
- Characterized by the presence of any one of the following:
- Trophic changes
- Absent or diminished pulses: examine distal pulses bilaterally, including
Buerger sign 
- With the patient in the supine position, elevate the lower limbs to a 45° angle at the hip.
- Evaluate for pallor of the feet.
- Ask the patient to sit up with their legs off of the examination table in the dependent position.
- Evaluate the time taken for the color to return to the feet and for the veins to become distended.
- Positive Buerger sign
- Bruit: over the affected artery may be heard in > 60–70% of cases with PAD
There are several classification systems for peripheral arterial disease, such as, the Rutherford classification, Global Limb Anatomic Staging System (GLASS), and the Trans-Atlantic Inter-Society Consensus (TASC). See “Overview of classification systems in peripheral artery disease” in the “Tips and Links” section below for details. 
Classification by clinical presentation 
- Asymptomatic (confirmed PAD in an asymptomatic individual)
- Critical limb ischemia (CLI) 
- Acute limb ischemia (ALI)
Wound, Ischemia, and foot Infection (WIfI) classification 
- The following factors are assigned values from 0 (normal) to 3 (severe abnormality):
- The benefit of revascularization and the risk of amputation can be estimated based on the three derived values.
Fontaine classification 
- Stage I: asymptomatic
- Stage II: pain on exertion
- Stage III: pain at rest
- Stage IV: necrosis, gangrene
- Acutely cold, painful limb: Suspect ALI, consult vascular surgery immediately for urgent revascularization. 
- Claudication, rest pain, or CLI
- PAD confirmed (based on clinical features and ABI) 
ALI is an imminently limb-threatening emergency and treatment should not be delayed to investigate the underlying etiology. 
Ankle-brachial index (ABI) 
- Ask the patient to rest in the supine position for approx. 10 minutes.
- Place the blood pressure cuffs on the ankles and the arms.
- Locate the pulse using the Doppler.
- Inflate the cuff until the pulse is no longer audible on the Doppler device, and then inflate the cuff by a further 20 mm Hg.
- Deflate the cuff slowly, and note the pressure at which the pulse is audible again.
- Ankle pressure
- Brachial pressure
- Calculate the ABI for each leg: Divide the highest ankle pressure by the highest brachial pressure.
|Ankle–brachial index interpretation in patients with suspected PAD |
|Resting ABI||Interpretation||Next steps|
|> 1.4|| || |
|1–1.4 || |
|≤ 0.9|| |
Exercise ABI 
- Description: ABI testing following extended exercise of the lower extremity
- Indication: suspicion of PAD in a patient with a normal or borderline ABI
- Findings: Either of the following are consistent with PAD.
Toe-brachial index 
- Definition: the ratio of the systolic blood pressure of the first toe to the systolic brachial blood pressure
- Findings: Toe-brachial index ≤ 0.70 is consistent with PAD.
Measures of tissue perfusion 
- Examples: transcutaneous oximetry, fluorescent imaging of indocyanine green dye, skin perfusion pressure
- Indication: nonhealing wounds or tissue loss suggestive of CLI
- Indications 
Angiography: preferred modality for assessment for revascularization
- Modalities 
- Findings: demonstration of site(s) and extent of arterial occlusion or stenosis and collateral blood flow
- Duplex ultrasound 
|Differential diagnosis of claudication|
|Patient characteristics||Clinical features|
|Arterial occlusion or narrowing||Vasculitides|| |
| || |
|Popliteal entrapment syndrome|| |
|Cystic adventitial disease|| || |
|Mimics of arterial occlusion|
The differential diagnoses listed here are not exhaustive.
First-line therapy 
- Structured exercise therapy
- Cardiovascular risk factor modification
- Persistent claudication despite first-line measures: Consider cilostazol (for symptomatic improvement) OR revascularization.
- First-line therapy 
- CLI: Consider revascularization in addition to structured exercise therapy and cardiovascular risk factor modification.
Management of complications
- ALI: immediate referral to vascular surgery (see “Treatment” in “Acute limb ischemia.”)
- Nonhealing ulcers
- Interdisciplinary care recommended
- Goal of care: complete wound healing 
Risk modification 
- PAD who smoke. should occur at every visit for all patients with
- Recommend avoiding passive smoke inhalation.
- Treatment of dyslipidemia
- Glycemic control (in patients with type 2 diabetes)
- Antihypertensive treatment
- Single-agent antiplatelet therapy ; : aspirin OR clopidogrel (ticagrelor may also be considered) 
Structured exercise therapy 
- Recommended first-line therapy for claudication
- Consider prior to revascularization. 
- Involves repetitive exercise until the onset of claudication with intervening periods of rest until the pain subsides
- Indications 
- Preferred agent: cilostazol; (a phosphodiesterase III (PDE3) inhibitor with vasodilatory, antiplatelet, and antithrombotic properties) 
- Important considerations
- , if the limb is viable
- Lifestyle-limiting claudication despite optimal medical therapy and exercise
- Endovascular or surgical revascularization
- The choice of procedure depends on the location and morphology of the arterial disease and the patient's comorbidities.
|Revascularization procedures for peripheral arterial disease|
|Endovascular revascularization||Surgical revascularization|
|Indications || || |
Supportive care 
- Foot care
- Provide multidisciplinary wound care to all patients with tissue loss.
- Consider adjunctive therapies (e.g., intermittent pneumatic compression) in patients unfit for revascularization. 
- Wet gangrene, unsalvageable limb: Urgent amputation may be required, especially in patients with sepsis.
- Dry gangrene: Consult vascular surgery to evaluate for revascularization prior to amputation.
Apart from , which is described in a separate article, the following complications can occur due to PAD.
- Definition: ulceration caused by impaired blood flow to the lower extremities
- Clinical features
- Differential diagnosis:
- Definition: a type of gangrenous necrosis caused by ischemia that is characterized by coagulative necrosis on histopathologic examination
- Areas with gray-black discoloration showing a clear demarcation between necrotic and viable tissue
- Autoamputation is possible.
- Diagnosis: based on clinical features
- Complications: wet gangrene
- Definition: a type of gangrenous necrosis caused by superinfection that is characterized by coagulative and liquefactive necrosis on histopathologic examination
- Clinical features
- Diagnosis: based on clinical features
- Complications: sepsis
We list the most important complications. The selection is not exhaustive.
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