What are the updated guidelines for managing peripheral arterial occlusive disease (PAOD)?

Updated Guidelines for Peripheral Arterial Occlusive Disease

The 2024 ESC Guidelines represent the most current evidence-based approach to managing peripheral arterial disease, emphasizing aggressive cardiovascular risk reduction with specific LDL-C targets <55 mg/dL, supervised exercise therapy as first-line treatment for claudication, and combination antithrombotic therapy (rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily) for high-risk patients. 1

Cardiovascular Risk Factor Management

Lipid-Lowering Therapy

• Target LDL-C <1.4 mmol/L (55 mg/dL) with >50% reduction from baseline in all PAD patients. 1
• Initiate high-intensity statin therapy immediately as first-line treatment. 1
• If target not achieved on maximally tolerated statin, add ezetimibe. 1
• If target still not achieved on statin plus ezetimibe, add PCSK9 inhibitor. 1
• For statin-intolerant patients not reaching goal on ezetimibe alone, add bempedoic acid with or without PCSK9 inhibitor. 1
• Fibrates are NOT recommended for cholesterol lowering. 1

This represents a significant shift from older ACC/AHA guidelines that recommended less aggressive LDL-C targets. 1

Blood Pressure Management

• Target systolic blood pressure 120-129 mmHg if tolerated (updated from previous 140/90 mmHg targets). 1
• In patients with unilateral renal artery stenosis, include ACE inhibitors or ARBs in the antihypertensive regimen. 1
• Beta-blockers are safe and effective in PAD patients and should not be withheld. 1, 2

Diabetes Management

• Target HbA1c <53 mmol/mol (7%) to reduce microvascular complications. 1
• Prioritize SGLT2 inhibitors with proven cardiovascular benefit to reduce cardiovascular events, independent of baseline HbA1c. 1, 3
• Prioritize GLP-1 receptor agonists with proven cardiovascular benefit to reduce cardiovascular events, independent of baseline HbA1c. 1, 3
• Individualize HbA1c targets based on comorbidities, diabetes duration, and life expectancy. 1
• Avoid hypoglycemia in PAD patients. 1
• Measure toe pressure or toe-brachial index if resting ABI is normal in diabetic patients. 1

Lifestyle Modifications

• Mediterranean diet is recommended for cardiovascular disease prevention. 1
• Low- to moderate-intensity aerobic activities (or high if tolerated) are recommended to increase overall and pain-free walking distance. 1
• Behavioral counseling for smoking cessation, healthy diet, and physical activity is essential. 1
• Smoking cessation pharmacotherapy should include varenicline, bupropion, and/or nicotine replacement therapy unless contraindicated. 1, 2

Antithrombotic Therapy

Monotherapy Options

• Aspirin 75-160 mg daily OR clopidogrel 75 mg daily as monotherapy. 1
• Clopidogrel is preferred based on CAPRIE trial data showing superior outcomes. 2
• Aspirin 75-325 mg daily is a safe alternative if clopidogrel not tolerated. 1, 2

Combination Therapy

• Rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily should be considered for patients with PAD and high ischemic risk who have non-high bleeding risk. 1
• This combination should be considered following lower-limb revascularization in patients with non-high bleeding risk. 1
• Aspirin for primary prevention may be considered in asymptomatic PAD patients with diabetes, absent contraindications. 1

This represents a major update from older guidelines that did not recommend combination antithrombotic therapy. 1

Exercise Therapy

Supervised Exercise Training (SET)

• SET is recommended as first-line treatment for symptomatic PAD before considering revascularization. 1, 2
• Minimum parameters: 30 minutes per session, at least 3 times weekly, for at least 12 weeks. 1, 2
• Walking training at high intensity (77-95% maximal heart rate or 14-17 on Borg scale) should be considered to improve walking performance. 1
• Training to moderate-severe claudication pain may be considered, though improvements achievable with lesser pain severities. 1
• SET is recommended as adjuvant therapy following endovascular revascularization. 1
• Alternative exercise modes (strength training, arm cranking, cycling) should be considered. 1

Pharmacologic Therapy for Claudication

Cilostazol

• Cilostazol 100 mg twice daily is the only FDA-approved medication specifically indicated to improve symptoms and walking distance in claudication (contraindicated in heart failure). 1, 4
• Should be considered as therapeutic trial in all patients with lifestyle-limiting claudication absent heart failure. 1

Pentoxifylline

• Pentoxifylline 400 mg three times daily may be considered as second-line alternative to cilostazol. 1, 4
• Clinical effectiveness is marginal and not well established. 1

Other Agents

• L-arginine, propionyl-L-carnitine, and ginkgo biloba have marginal or unestablished effectiveness. 1
• Chelation therapy is NOT indicated and may cause harmful adverse effects. 1

Diagnostic Approach

Initial Testing

• Duplex ultrasound (DUS) is recommended as first-line imaging to confirm PAD lesions. 1
• Resting ankle-brachial index (ABI) for patients with history or examination findings suggesting PAD. 2
• Measure toe pressure or toe-brachial index if resting ABI is normal in diabetic or renal failure patients. 1

Advanced Imaging

• CTA and/or MRA are recommended as adjuvant imaging for symptomatic patients with aorto-iliac or multisegmental/complex disease when preparing for revascularization. 1
• Analyze anatomical imaging in conjunction with symptoms and hemodynamic tests prior to invasive procedures. 1

Revascularization Strategy

Indications for Intervention

• After 3 months of optimal medical therapy (OMT) and exercise therapy, assess PAD-related quality of life. 1
• If PAD-related quality of life remains impaired after 3 months of OMT and exercise, revascularization may be considered. 1, 2
• Patients must have lifestyle-limiting disability with inadequate response to exercise/pharmacotherapy AND/OR very favorable risk-benefit ratio. 1

What NOT to Do

• Revascularization is NOT recommended solely to prevent progression to chronic limb-threatening ischemia (CLTI). 1
• Revascularization is NOT recommended in asymptomatic PAD. 1
• Endovascular intervention is NOT indicated as prophylactic therapy. 1

Technical Considerations

• Drug-eluting treatment should be considered first-choice strategy for femoro-popliteal lesions. 1
• Open surgical approach with autologous vein should be considered for femoro-popliteal lesions when available in low surgical risk patients. 1
• Endovascular intervention is preferred for TASC type A iliac and femoropopliteal lesions. 1
• Stenting is effective as primary therapy for common and external iliac artery stenoses/occlusions. 1
• Primary stent placement is NOT recommended in femoral, popliteal, or tibial arteries. 1
• Provisional stenting indicated for iliac arteries as salvage for suboptimal balloon dilation result. 1

Chronic Limb-Threatening Ischemia (CLTI)

Management Principles

• Early recognition and referral to vascular team are recommended for limb salvage. 1
• Perform revascularization as soon as possible in CLTI patients. 1
• Use autologous veins as preferred conduit for infra-inguinal bypass surgery. 1
• In multilevel disease, eliminate inflow obstructions when treating. 1
• Offloading mechanical tissue stress is indicated for CLTI patients with ulcers to allow wound healing. 1
• Lower-limb exercise training is NOT recommended in CLTI patients with wounds. 1

Follow-Up and Monitoring

• Regular follow-up at least once yearly, assessing clinical/functional status, medication adherence, limb symptoms, cardiovascular risk factors, with DUS as needed. 1, 2
• Patients with prior CLTI should be evaluated at least twice annually by vascular specialist due to high recurrence risk. 2

Common Pitfalls to Avoid

• Do NOT withhold beta-blockers in PAD patients—they are safe and effective. 1, 2
• Do NOT use anticoagulation solely for cardiovascular event reduction in PAD (increases bleeding without benefit). 2
• Do NOT proceed to revascularization without first attempting 3 months of supervised exercise and optimal medical therapy. 1, 2
• Do NOT use fibrates for cholesterol lowering in PAD. 1
• Do NOT perform revascularization in asymptomatic patients or solely to prevent progression to CLTI. 1