What are the symptoms and treatment options for Peripheral Arterial Disease (PAD)?

Symptoms of Peripheral Arterial Disease

The classic symptom of PAD is intermittent claudication—reproducible cramping, aching, or pain in the calves, thighs, or buttocks that occurs with exertion and resolves within 10 minutes of rest—but only about 10% of patients present with this classic pattern. 1, 2

Clinical Presentation Spectrum

Symptomatic Presentations

Most patients with PAD (approximately 50%) experience atypical leg symptoms rather than classic claudication, including: 1, 2

• Pain or discomfort that begins at rest but worsens with exertion 1
• Pain or discomfort that does not stop walking 1
• Pain or discomfort that begins with exertion but is not relieved within 10 minutes of rest 1
• Heaviness and leg discomfort 1
• Leg fatigue or weakness 1

Approximately 40% of patients with PAD are completely asymptomatic, yet still demonstrate significant functional impairment comparable to those with claudication. 1, 3

Advanced Disease (Chronic Limb-Threatening Ischemia)

CLTI represents the most severe form of PAD and presents with: 1

• Ischemic rest pain (severe pain at rest, often localized to the forefoot, influenced by dependency) 1
• Non-healing wounds or ulcers 1
• Gangrene 1
• Risk of amputation 1

Physical Examination Findings

Key examination findings suggestive of PAD include: 1

• Diminished or absent lower extremity pulses (femoral, popliteal, dorsalis pedis, posterior tibial) 1
• Femoral bruits 1
• Cold feet 1
• Atrophy of subcutaneous tissues 1
• Hair loss on the lower extremities 1
• Non-healing wounds 1

The absence of the posterior tibial pulse is more accurate for PAD diagnosis than absence of the dorsalis pedis pulse, as the latter can be congenitally absent in healthy individuals. 1

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Treatment Options

First-Line Therapies (Guideline-Directed Management)

Structured supervised exercise therapy is a Class I recommendation and should be the cornerstone of initial treatment for symptomatic PAD. 1

• Supervised exercise programs involving walking approximately 5 times per week at significant intensity improve walking distance by 28% to 100% 4, 5
• Exercise improves pain-free walking distance, maximal walking distance, and quality of life 1, 6
• Benefits extend beyond hemodynamic improvements through mechanisms including reduced inflammation, improved cardiovascular fitness, angiogenesis, and enhanced mitochondrial function 1, 5

Pharmacological Management

Medical therapy for PAD includes: 1, 2

• Antiplatelet therapy: Clopidogrel is preferred over aspirin 2, 7
• High-intensity statin therapy for lipid management and cardiovascular risk reduction 2, 7
• Cilostazol 100 mg twice daily (Class I indication): FDA-approved for reducing symptoms of intermittent claudication and increasing walking distance 1, 4
• ACE inhibitors or ARBs for blood pressure control and cardiovascular protection 2, 7, 3
• GLP-1 receptor agonists and SGLT-2 inhibitors for patients with diabetes 2

Cilostazol demonstrates statistically significant improvements in both claudication onset distance and maximal walking distance, with effects seen as early as 2-4 weeks of therapy. 4

Pain Management Considerations

Pain management in PAD should follow a multimodal approach: 1

• First-line: Supervised exercise therapy and cilostazol (both Class I indications) 1
• Adjunctive options: NSAIDs (with caution for renal/cardiac risks), gabapentinoids for neuropathic pain components 1
• Neither opioid nor non-opioid analgesics are specifically recommended in current PAD guidelines 1
• For patients with concurrent diabetic neuropathy, additional screening and neuropathic pain agents may be warranted 1

Lifestyle Modifications

Critical lifestyle interventions include: 1, 2, 7

• Smoking cessation (physician advice, nicotine replacement therapy, bupropion) 7, 3
• Cardiovascular risk factor modification 1
• Preventive foot care 1

Revascularization

Revascularization (endovascular or surgical) should be reserved for patients with: 1

• Functionally limiting claudication with inadequate response to guideline-directed medical therapy and structured exercise 1
• Chronic limb-threatening ischemia 1
• Acute limb ischemia (requires urgent evaluation) 2, 3

Revascularization is NOT recommended for asymptomatic PAD, as it increases risk of major adverse limb events without altering natural history. 1

Common Pitfalls

Key diagnostic considerations: 1

• Do not rely solely on classic claudication symptoms—actively inquire about atypical leg symptoms and perceived walking impairment in all at-risk patients 1
• Presence of dorsalis pedis and posterior tibial pulses does not rule out ischemic changes in the forefoot 1
• An ankle-brachial index ≥1.4 is noncompressible (common in diabetes and end-stage renal disease) and requires alternative testing 2

Treatment sequencing: 1

• Always initiate guideline-directed medical therapy and structured exercise before considering revascularization for claudication 1
• Patients with CLTI require expedited evaluation and treatment to prevent amputation 1