What is the recommended management of peripheral artery disease?

Management of Peripheral Artery Disease

Clopidogrel 75 mg daily is the preferred antiplatelet agent for all symptomatic PAD patients, combined with high-intensity statin therapy, blood pressure control to <140/90 mmHg (<130/80 mmHg if diabetic), smoking cessation, and supervised exercise training (30–45 minutes, ≥3 times weekly for ≥12 weeks) as mandatory first-line therapy; revascularization is reserved exclusively for patients with lifestyle-limiting symptoms that persist after a full 3-month trial of this optimal medical regimen. 1

Initial Assessment

Perform a systematic vascular evaluation that includes:

• Detailed symptom review assessing walking impairment, claudication distance (how far before pain starts), ischemic rest pain, and presence of non-healing wounds 1, 2
• Comprehensive pulse examination of all lower extremity pulses (femoral, popliteal, dorsalis pedis, posterior tibial) 1, 2
• Direct foot inspection with shoes and socks removed to identify ulcers, skin changes, or tissue loss 1, 2
• Bilateral arm blood pressure measurement to detect subclavian stenosis (difference >15–20 mmHg is significant) 2
• Ankle-brachial index (ABI) as the initial diagnostic test; ABI ≤0.90 confirms PAD 2
• Post-exercise ABI if resting ABI is normal but clinical suspicion remains high (>20% decrease is diagnostic) 2
• Toe-brachial index for patients with non-compressible vessels (ABI >1.40, common in diabetes) 2

Antiplatelet Therapy (Mandatory for All PAD Patients)

Clopidogrel 75 mg once daily is the first-choice antiplatelet agent because it provides superior reduction in myocardial infarction, stroke, and vascular death compared with aspirin. 1, 3

• Aspirin 75–100 mg daily is an acceptable alternative only when clopidogrel is contraindicated or not tolerated 1, 3
• In asymptomatic PAD with ABI ≤0.90, antiplatelet therapy is reasonable for cardiovascular risk reduction 1
• For high-risk PAD patients (especially after lower-limb revascularization) without high bleeding risk, add rivaroxaban 2.5 mg twice daily to aspirin 100 mg daily to further reduce cardiovascular and limb events 3
• Routine dual antiplatelet therapy (aspirin + clopidogrel) is NOT recommended because it increases major bleeding without demonstrable cardiovascular benefit 1, 3
• Warfarin anticoagulation must never be added to antiplatelet therapy for PAD; it provides no cardiovascular benefit and markedly increases major bleeding risk 1, 3

Lipid Management (Mandatory for All PAD Patients)

High-intensity statin therapy is mandatory immediately upon PAD diagnosis, regardless of baseline cholesterol levels. 1, 3

• Target LDL-C <100 mg/dL for standard PAD patients, and <70 mg/dL for very high-risk patients 3
• For statin-intolerant patients, add bempedoic acid alone or combined with a PCSK9 inhibitor 3
• Fibrates are NOT recommended for cholesterol lowering in PAD 3

Blood Pressure Control

Target blood pressure <140/90 mmHg in patients without diabetes, and <130/80 mmHg in patients with diabetes or chronic kidney disease. 1, 2, 3

• ACE inhibitors or ARBs are preferred first-line agents for cardiovascular protection in PAD 1
• Beta-blockers are safe and effective in PAD and should NOT be withheld; they are not contraindicated 1, 2, 3

Smoking Cessation (Critical Priority)

Screen for tobacco use at every single visit and offer pharmacotherapy unless contraindicated. 1

• Provide one or more of: varenicline, bupropion, or nicotine replacement therapy 1, 3
• Offer counseling and develop a comprehensive quit plan 1, 3

Diabetes Management

Target HbA1c <7% to reduce microvascular complications. 1, 3

• SGLT2 inhibitors and GLP-1 receptor agonists with proven cardiovascular benefit are recommended for patients with type 2 diabetes and PAD to reduce cardiovascular events 3
• Implement daily foot inspection, appropriate footwear, chiropody/podiatry, skin cleansing, moisturizers, and prompt treatment of any lesions 1
• Patients with diabetes who have ABI <0.4 or any diabetic patient with known PAD require regular foot inspections to prevent ulceration and amputation 1, 3

Supervised Exercise Training (First-Line Treatment for Claudication)

Supervised exercise training (SET) is the initial treatment for intermittent claudication before any consideration of revascularization and carries a Class I, Level A recommendation. 1, 3

Exercise Prescription Parameters:

• Frequency: ≥3 sessions per week 1, 3
• Duration: 30–60 minutes per session 1, 3
• Program length: Minimum 12 weeks 1, 3
• Intensity: High-intensity (77–95% of maximal heart rate or Borg 14–17) yields the greatest improvements 3
• Modality: Walking is the first-line training activity 3
• Pain level: Exercise to moderate-severe claudication pain to maximize walking distance gains 3

When SET is unavailable, structured home-based exercise training (HBET) with remote monitoring may be offered, although it is inferior to supervised programs. 3

The CLEVER trial demonstrated that supervised exercise training produced significantly greater treadmill walking distance at 6 months compared with primary stenting for aorto-iliac PAD. 3

Pharmacologic Therapy for Claudication Symptoms

Cilostazol 100 mg twice daily should be added when lifestyle-limiting claudication persists after ≥3 months of optimal medical therapy and supervised exercise. 1, 3

• Cilostazol is the most effective medication for improving symptoms and walking distance 1, 3
• Cilostazol is absolutely contraindicated in any degree of heart failure because of its phosphodiesterase-III inhibition 1, 3
• Pentoxifylline 400 mg three times daily may be used as a second-line alternative only when cilostazol is contraindicated or not tolerated; its clinical benefit is marginal and not well established 1, 3

Indications for Revascularization (Only After 3-Month Trial)

Revascularization should be considered ONLY after a full 3-month trial of optimal medical therapy and supervised exercise in patients with persistent lifestyle-limiting symptoms. 1, 3

All of the Following Criteria Must Be Met:

• Completion of supervised exercise and pharmacotherapy with inadequate symptomatic response 1, 3
• Significant disability affecting work or important daily activities (not just mild discomfort) 1, 3
• Ongoing comprehensive risk-factor modification and antiplatelet therapy already implemented 1, 3
• Lesion anatomy that presents low procedural risk and high probability of immediate and long-term technical success 1, 3

After the 3-month period, reassess PAD-related quality of life; revascularization may be pursued if quality of life remains impaired. 3

Revascularization Strategy:

• For femoro-popliteal lesions, drug-eluting endovascular therapy is the preferred first-line strategy 3
• Open surgical bypass using autologous vein should be considered in low-risk patients when a suitable vein is available 3
• For TASC type A iliac and femoropopliteal lesions, endovascular intervention is preferred 2

Revascularization is NOT indicated in asymptomatic PAD patients or solely to prevent progression to critical limb-threatening ischemia. 3

A large Dutch registry of 54,504 patients demonstrated that patients who underwent revascularization (endovascular or open) experienced higher rates of secondary procedures and increased 5-year mortality relative to those managed with SET alone. 3

Critical Limb-Threatening Ischemia (CLTI) – Urgent Management

Early recognition of CLTI and immediate referral to a vascular team are essential for limb salvage. 3

• Urgently assess and treat amputation risk factors in CLTI patients 1, 3
• Perform cardiovascular risk assessment before open surgical repair 1
• Start systemic antibiotics promptly if skin ulceration with infection is present 1, 3
• Off-loading of mechanical tissue stress is indicated for CLTI-related ulcers to facilitate wound healing 3
• Revascularization should be performed as soon as possible for limb salvage 3
• Exercise training is contraindicated in CLTI patients with wounds 3

High-Risk Patients Requiring Regular Foot Inspection:

• Patients with ABI <0.4 and diabetes 1, 3
• Any diabetic patient with known PAD 1, 3
• Acute limb symptoms in diabetics, neuropathy, chronic renal failure, or infection constitute vascular emergencies requiring immediate assessment 3

Acute Limb Ischemia

In patients with acute limb ischemia and a salvageable extremity, emergent evaluation of the occlusion level and prompt endovascular or surgical revascularization are required. 1

If the limb is non-viable, vascular anatomy evaluation and revascularization attempts should not be performed. 1

Post-Revascularization Antiplatelet Strategy

Continue long-term single antiplatelet therapy (aspirin 75–100 mg daily OR clopidogrel 75 mg daily) after any revascularization. 1

• For below-knee bypass using prosthetic grafts, consider dual antiplatelet therapy (aspirin + clopidogrel) for 12 months 1
• For all other revascularization procedures, single antiplatelet therapy remains preferred 1

Follow-Up and Surveillance

All PAD patients require at least annual follow-up to assess clinical status, medication adherence, limb symptoms, and cardiovascular risk factors, with duplex ultrasound as needed. 2, 3

• Patients with prior CLTI should be evaluated by a vascular specialist at least twice yearly due to high recurrence risk 1, 2, 3
• Long-term patency of infrainguinal bypass grafts should be monitored through a surveillance program including vascular history, resting ABI, physical examination, and periodic duplex ultrasound 2, 3
• Post-revascularization surveillance: ABI and arterial duplex ultrasound at 1–3 months, 6 months, 12 months, then annually 3
• Patients at risk for or treated for CLTI should receive verbal and written instructions for self-surveillance of recurrence 3

Common Pitfalls to Avoid

Do NOT proceed directly to revascularization without first completing a full 3-month trial of optimal medical therapy and supervised exercise training in patients with intermittent claudication. 1, 3

Do NOT withhold beta-blockers; they are safe and effective in PAD and are not contraindicated. 1, 2, 3

Do NOT add warfarin to antiplatelet therapy without a clear indication (e.g., atrial fibrillation); it increases major bleeding without cardiovascular benefit in PAD. 1, 3

Do NOT prescribe cilostazol to patients with any degree of heart failure because it is absolutely contraindicated. 1, 3

Do NOT delay referral to a vascular team in patients with CLTI; early recognition and treatment are critical for limb salvage. 3

Do NOT perform arterial imaging in patients with a normal post-exercise ABI unless alternative diagnoses (e.g., entrapment syndromes) are suspected. 1, 3