What is the recommended treatment for a patient with peripheral artery disease (PAD)?

Treatment of Peripheral Artery Disease

All patients with PAD require comprehensive guideline-directed medical therapy (GDMT) including antiplatelet therapy, high-intensity statin therapy, blood pressure control, smoking cessation, and supervised exercise training, with revascularization reserved only for those with lifestyle-limiting symptoms that persist after 3 months of optimal medical therapy. 1

Antiplatelet Therapy

Clopidogrel 75 mg daily is the preferred antiplatelet agent to reduce myocardial infarction, stroke, and vascular death in symptomatic PAD patients. 1, 2, 3 Aspirin 75-100 mg daily is an acceptable alternative. 1, 4

• For PAD patients with high ischemic risk and non-high bleeding risk, combination therapy with rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily should be considered to further reduce cardiovascular events. 1, 4
• This combination is also recommended following lower-limb revascularization in patients without high bleeding risk. 1, 4
• Long-term dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel is NOT recommended for PAD alone. 1
• For asymptomatic PAD patients with diabetes, aspirin 75-100 mg may be considered for primary prevention. 1, 4

Lipid Management

All PAD patients must receive high-intensity statin therapy immediately upon diagnosis, regardless of baseline cholesterol levels. 2, 4 Target LDL-C <100 mg/dL, with <70 mg/dL reasonable for very high-risk patients. 4

• For statin-intolerant patients not achieving LDL-C goals on ezetimibe, add bempedoic acid alone or combined with a PCSK9 inhibitor. 1
• Fibrates are NOT recommended for cholesterol lowering. 1

Blood Pressure Control

Target blood pressure <140/90 mmHg in most patients, or <130/80 mmHg in those with diabetes or chronic kidney disease. 1, 4

• Beta-blockers are NOT contraindicated in PAD and are effective antihypertensive agents. 2, 4
• ACE inhibitors should be considered to reduce adverse cardiovascular events. 4

Diabetes Management

Target HbA1c <7% (53 mmol/mol) to reduce microvascular complications. 1, 4

• 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, independent of baseline HbA1c. 1
• Avoid hypoglycemia and individualize HbA1c targets based on comorbidities, diabetes duration, and life expectancy. 1
• Implement immediate foot care: appropriate footwear, daily foot inspection, skin cleansing, topical moisturizing creams, and urgent attention to any skin lesions or ulcerations. 4

Exercise Therapy

Supervised exercise training (SET) is the first-line treatment for intermittent claudication before considering revascularization. 1, 5

• Exercise sessions should be performed at least 3 times per week, for at least 30 minutes per session, for a minimum of 12 weeks. 1, 5, 4
• Walking should be the first-line training modality, performed at high intensity (77-95% of maximal heart rate or 14-17 on Borg's scale). 1
• When walking is not an option, alternative modes (strength training, arm cranking, cycling) should be considered. 1
• SET is also recommended as adjuvant therapy for patients undergoing endovascular revascularization. 1
• When SET is not available, a structured and monitored home-based exercise therapy (HBET) program with calls, logbooks, or connected devices should be considered. 1

Pharmacotherapy for Claudication

Cilostazol 100 mg twice daily should be considered for all patients with lifestyle-limiting claudication (contraindicated in heart failure). 1, 5

• Cilostazol is effective at improving symptoms and increasing walking distance. 1
• Side effects include headache, diarrhea, dizziness, and palpitations; approximately 20% of patients discontinue within 3 months. 1
• Pentoxifylline 400 mg three times daily may be considered as a second-line alternative, though its clinical effectiveness is marginal and not well established. 1, 5

Smoking Cessation

Ask about tobacco use at every encounter, provide counseling, and develop a quit plan with pharmacotherapy. 4

• Offer one or more of: varenicline, bupropion, or nicotine replacement therapy, unless contraindicated. 4

Revascularization Criteria

Revascularization should only be considered after a 3-month trial of optimal medical therapy and exercise therapy in patients with persistent lifestyle-limiting symptoms and impaired quality of life. 1, 5, 4

Patients must meet ALL of the following criteria before revascularization: 1, 2

• Inadequate response to exercise therapy and pharmacotherapy
• Significant disability affecting work or important activities
• Comprehensive risk factor modification and antiplatelet therapy already implemented
• Lesion anatomy with low procedural risk and high probability of initial and long-term success

Revascularization is NOT recommended solely to prevent progression to chronic limb-threatening ischemia (CLTI). 1, 4

Revascularization is NOT recommended for asymptomatic PAD. 1

Revascularization Approach

• Endovascular intervention is the preferred technique for TASC type A iliac and femoropopliteal lesions. 1, 2
• For femoropopliteal lesions, drug-eluting treatment should be considered as first-choice strategy. 1
• Open surgical approach should be considered when autologous vein (e.g., great saphenous vein) is available in low surgical risk patients. 1
• Adapt the mode and type of revascularization to anatomical lesion location, lesion morphology, and general patient condition. 1, 4

Follow-Up Protocol

Regular follow-up at least once annually is required to assess clinical and functional status, medication adherence, limb symptoms, and cardiovascular risk factors, with duplex ultrasound as needed. 1, 2, 4

• Post-revascularization surveillance: ABI and arterial duplex ultrasound at 1-3 months, 6 months, 12 months, then annually. 4
• Immediate ABI and duplex ultrasound if new lower extremity signs or symptoms develop. 4

Critical Limb-Threatening Ischemia (CLTI)

Early recognition of CLTI and immediate referral to a vascular team for limb salvage is mandatory. 1, 4

• Revascularization is recommended for limb salvage in CLTI patients and should be performed as soon as possible. 1, 4
• Patients at risk for CLTI (ABI <0.4 with diabetes, or any diabetic with known PAD) should undergo regular foot inspection. 1
• Systemic antibiotics should be initiated promptly in patients with CLI, skin ulcerations, and evidence of limb infection. 1
• Refer patients with CLI and skin breakdown to healthcare providers with specialized wound care expertise. 1
• Patients with prior history of CLI should be evaluated at least twice annually by a vascular specialist due to high recurrence risk. 1, 2

Common Pitfalls to Avoid

• Do not withhold beta-blockers in PAD patients who need them for other indications (e.g., coronary disease, heart failure); they are not contraindicated. 2, 4
• Do not perform revascularization without first completing a 3-month trial of optimal medical therapy and supervised exercise. 1, 5
• Do not use long-term DAPT (aspirin plus clopidogrel) routinely in PAD patients without another indication. 1
• Do not screen with arterial imaging (CTA, MRA) in asymptomatic PAD patients; this should only be done when planning revascularization in symptomatic patients. 1