What are the treatment options for peripheral arterial disease (PAD)?

Treatment Options for Peripheral Arterial Disease

All patients with PAD require a comprehensive treatment strategy combining supervised exercise therapy, aggressive risk factor modification with statins and antiplatelet agents, and selective revascularization for those with lifestyle-limiting symptoms despite optimal medical therapy. 1, 2

Risk Factor Modification (Foundation of Treatment)

Smoking Cessation (Highest Priority)

• Every patient who smokes must be counseled at every visit and offered pharmacotherapy including varenicline, bupropion, or nicotine replacement therapy 1
• Smoking cessation is the single most critical intervention to prevent disease progression and reduce cardiovascular mortality 2

Lipid Management

• Statin therapy is mandatory for all PAD patients regardless of baseline cholesterol levels 1, 2
• Target LDL-C <70 mg/dL for very high-risk patients (those with symptomatic PAD or prior cardiovascular events) 2
• Consider adding PCSK9 inhibitors if LDL targets not achieved with maximally tolerated statin therapy 1
• Icosapent ethyl 2g twice daily may be considered if triglycerides remain >1.5 mmol/L despite statin therapy 1

Blood Pressure Control

• Antihypertensive therapy is essential to reduce MI, stroke, heart failure, and cardiovascular death 1
• Target BP <140/90 mmHg (or <130/80 mmHg if diabetes or chronic kidney disease present) 2
• Beta-blockers are safe and effective in PAD—they are NOT contraindicated despite historical concerns 1
• ACE inhibitors should be considered as they provide additional cardiovascular protection beyond BP lowering 1

Diabetes Management

• Target HbA1c <7% to reduce microvascular complications and potentially improve cardiovascular outcomes 1
• Meticulous foot care is mandatory: daily inspection, appropriate footwear, prompt treatment of any skin lesions or ulcerations 1

Exercise Therapy (First-Line for Claudication)

Supervised Exercise Training (SET)

• SET is the most effective initial treatment for intermittent claudication and is recommended as first-line therapy 1, 2
• Minimum program requirements: 30-45 minutes per session, at least 3 times weekly, for minimum 12 weeks 1
• Walking is the preferred modality; exercise to moderate-severe claudication pain for maximum benefit 1
• High-intensity training (77-95% maximal heart rate or 14-17 on Borg scale) should be considered for optimal walking performance 1
• For patients undergoing endovascular revascularization, SET is recommended as adjuvant therapy 1

Home-Based Exercise

• When SET is unavailable, structured and monitored home-based exercise programs (using calls, logbooks, or connected devices) should be considered 1
• Alternative modes (strength training, arm cranking, cycling) can be used when walking is not feasible 1

Antithrombotic Therapy

For Symptomatic PAD

• Single antiplatelet therapy is the standard: aspirin 75-100 mg daily OR clopidogrel 75 mg daily 1, 2, 3
• Clopidogrel is preferred based on 23.8% relative risk reduction versus aspirin in the CAPRIE trial 1
• For high ischemic risk patients with non-high bleeding risk: rivaroxaban 2.5 mg twice daily PLUS aspirin 100 mg daily should be considered 1
• This dual pathway inhibition strategy is particularly important following lower-limb revascularization 1

For Asymptomatic PAD

• Antiplatelet therapy can be useful in asymptomatic patients with ABI ≤0.90 1
• Aspirin 75-100 mg may be considered for primary prevention in asymptomatic PAD patients with diabetes 1

Important Caveat

• Dual antiplatelet therapy (aspirin + clopidogrel) without rivaroxaban is NOT routinely recommended as there is no evidence of superiority over single agent therapy 1
• Oral anticoagulation with warfarin alone is NOT indicated for PAD 1

Revascularization

Indications

• Revascularization should be considered ONLY after 3 months of optimal medical therapy (OMT) and exercise therapy in symptomatic patients with impaired quality of life 1
• Immediate revascularization is indicated for: chronic limb-threatening ischemia (CLTI) with rest pain, ulceration, or gangrene 1
• Revascularization is NOT recommended solely to prevent progression to CLTI 1
• Asymptomatic PAD is NOT an indication for revascularization 1

Technical Approach

• The mode and type of revascularization must be adapted to anatomical lesion location, morphology, and patient surgical risk 1
• For femoropopliteal lesions, drug-eluting devices should be considered first-line for endovascular approach 1
• Open surgical bypass with autologous vein should be considered for femoropopliteal disease in low surgical risk patients when great saphenous vein is available 1

Follow-Up and Monitoring

• Regular follow-up at least annually is mandatory to assess clinical/functional status, medication adherence, limb symptoms, and cardiovascular risk factors 1, 2
• Duplex ultrasound assessment should be performed as needed 1
• Screen all PAD patients for abdominal aortic aneurysm given high prevalence of concurrent aortic disease 2

Critical Pitfalls to Avoid

• Never discontinue antiplatelet therapy without compelling reason—this dramatically increases cardiovascular event risk 3
• If surgery requires temporary discontinuation, stop clopidogrel 5 days prior and resume as soon as hemostasis achieved 3
• Avoid omeprazole or esomeprazole in patients on clopidogrel—these significantly reduce clopidogrel's antiplatelet activity via CYP2C19 inhibition 3
• Do not delay revascularization in CLTI—early recognition and vascular team referral are essential for limb salvage 1
• Optimal care for CLTI requires multidisciplinary vascular team management 1, 2