What is the management of peripheral arterial disease (PAD)?

Management of Peripheral Arterial Disease

All patients with PAD require comprehensive optimal medical therapy including supervised exercise training, high-intensity statin therapy, antiplatelet therapy (or dual pathway inhibition in selected patients), and aggressive cardiovascular risk factor modification to reduce major adverse cardiovascular events, major adverse limb events, and improve quality of life. 1, 2

Initial Assessment and Risk Stratification

• Perform vascular symptom review assessing walking impairment, claudication, ischemic rest pain, and nonhealing wounds 1
• Conduct comprehensive pulse examination and foot inspection with shoes and socks removed 1
• Screen for abdominal aortic aneurysm in all symptomatic PAD patients over 50 years old 1, 2
• Measure ankle-brachial index (ABI); if normal but symptoms persist, obtain post-exercise ABI 1
• Use toe-brachial index when ABI is falsely elevated (>1.4) due to arterial calcification in patients with diabetes or renal failure 2

Lifestyle Modifications (Foundation of All PAD Management)

Smoking Cessation

• Implement comprehensive smoking cessation interventions combining behavioral counseling with pharmacotherapy (nicotine replacement, bupropion, or varenicline) 2, 3
• This is non-negotiable for all PAD patients who smoke 2

Supervised Exercise Training (First-Line Therapy for Claudication)

• Prescribe supervised exercise training at least 3 sessions per week, 30-60 minutes per session, for minimum 12 weeks 1, 2, 3
• Exercise to moderate-to-severe claudication pain for optimal benefit, though improvements occur with lesser pain severities 1, 2
• Progressively increase exercise training load every 1-2 weeks based on patient tolerance 1
• Do not prescribe exercise training for patients with CLTI and open wounds 1

Pharmacological Management

Antiplatelet/Antithrombotic Therapy

For symptomatic PAD without high bleeding risk:

• Combination therapy with rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily is preferred to reduce both major adverse cardiovascular events and major adverse limb events 1, 2, 3
• This dual pathway inhibition strategy is also recommended following lower-limb revascularization 1, 2

For patients with contraindications to dual therapy or high bleeding risk:

• Clopidogrel 75 mg daily is preferred over aspirin alone 2, 3, 4
• Aspirin 75-100 mg daily is an alternative 2, 3

For asymptomatic PAD with diabetes:

• Consider aspirin 75-100 mg daily for primary prevention in absence of contraindications 1

Lipid Management

• Prescribe high-intensity statin therapy for all PAD patients regardless of baseline LDL-C 2, 3
• Target LDL-C <70 mg/dL (or <55 mg/dL per European guidelines) 2, 3
• Aim for LDL-C reduction ≥50% from baseline 3

Blood Pressure Management

• Target <140/90 mmHg in non-diabetics or <130/80 mmHg in diabetics and those with chronic kidney disease 3
• Prefer ACE inhibitors as they provide additional cardiovascular protection beyond blood pressure reduction 2
• Do not withhold beta-blockers in PAD patients—they are safe and effective, particularly when coronary artery disease coexists 2

Diabetes Management

• Target hemoglobin A1C <7% to reduce microvascular complications 3

Symptom-Specific Pharmacotherapy

• Cilostazol 100 mg twice daily improves walking distance and symptoms in patients with intermittent claudication without heart failure 3, 5

Revascularization Decision Algorithm

For Intermittent Claudication:

• First, provide 3 months of optimal medical therapy plus supervised exercise training 1, 2, 3
• After 3 months, assess PAD-related quality of life 1
• Consider revascularization only if:
  1. Significant lifestyle-limiting disability persists despite optimal medical therapy 1
  2. Patient has impaired PAD-related quality of life 1, 2
  3. Lesion anatomy suggests low risk and high probability of success 1
  4. Patient has received comprehensive risk factor modification and antiplatelet therapy 1

Critical pitfall: Revascularization is NOT recommended solely to prevent progression to CLTI 1

Critical pitfall: Revascularization is NOT recommended for asymptomatic PAD 1

For Chronic Limb-Threatening Ischemia (CLTI):

• Perform expedited evaluation and immediate revascularization as soon as possible to prevent limb loss 1
• Manage patients with CLTI through a multidisciplinary vascular team 1
• Initiate systemic antibiotics promptly if skin ulcerations with limb infection present 1
• Refer to specialized wound care providers 1
• Implement offloading mechanical tissue stress for ulcer healing 1
• Assess cardiovascular risk before open surgical repair 1
• Evaluate for aneurysmal disease if atheroembolization features present 1

Revascularization Technical Considerations:

• Adapt revascularization mode to anatomical lesion location, morphology, and patient condition 1
• For femoro-popliteal lesions, drug-eluting treatment is first-choice endovascular strategy 1
• Consider open surgical approach with autologous vein (e.g., great saphenous vein) for femoro-popliteal lesions in low surgical risk patients 1
• For CLTI with good autologous veins and low surgical risk, consider infra-inguinal bypass 1
• Endovascular treatment may be considered first-line for CLTI patients with increased surgical risk 1
• In multilevel vascular disease, eliminate inflow obstructions when treating downstream lesions 1

Surveillance and Follow-Up

Regular Monitoring:

• Follow all PAD patients at least annually (minimum once yearly) 1, 2, 3
• Assess clinical and functional status, medication adherence, limb symptoms, and cardiovascular risk factors 1, 2, 3
• Perform duplex ultrasound assessment as needed 1, 3

High-Risk Populations:

• Patients with prior CLI or successfully treated CLI require evaluation at least twice annually by a vascular specialist due to high recurrence risk 1
• Patients at risk of CLI (ABI <0.4 with diabetes, or any diabetic with known PAD) require regular foot inspection 1
• Directly examine feet with shoes and socks removed at regular intervals after successful CLI treatment 1

Special Populations and Comorbidities

PAD with Atrial Fibrillation:

• These patients have 40% higher all-cause mortality and >70% higher major adverse cardiovascular events risk compared to atrial fibrillation without PAD 2
• Balance anticoagulation decisions between stroke prevention and bleeding risk 2

PAD with Heart Failure:

• Concomitant heart failure increases major adverse cardiovascular events risk by 30% and mortality by 40% 2
• Optimize heart failure therapy and intensify risk factor modification in these high-risk patients 2

PAD with Chronic Wounds:

• Apply the WIfI (Wound, Ischemia, foot Infection) classification to estimate amputation risk 2

Critical Pitfalls to Avoid

• PAD patients are frequently undertreated compared to those with coronary disease—ensure all secondary prevention measures are implemented 2
• Do not perform arterial imaging for patients with normal post-exercise ABI unless other causes suspected (e.g., entrapment syndromes, isolated internal iliac artery occlusive disease) 1
• Avoid concomitant use of clopidogrel with omeprazole or esomeprazole as they significantly reduce antiplatelet activity 4
• When clopidogrel must be temporarily discontinued (e.g., for surgery with major bleeding risk), interrupt therapy for five days prior and restart as soon as hemostasis achieved 4
• Consider alternative P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers 4