What is the first line of treatment for Peripheral Arterial Occlusive Disease (PAOD)?

First-Line Treatment for Peripheral Arterial Occlusive Disease (PAOD)

The first-line treatment for PAOD is optimal medical therapy (OMT) consisting of supervised exercise training (SET) combined with comprehensive cardiovascular risk factor modification, including statin therapy, antiplatelet therapy, and lifestyle modifications—revascularization should only be considered after a 3-month trial of OMT in patients with persistent lifestyle-limiting symptoms. 1

Supervised Exercise Training as Primary Therapy

SET is the most effective first-line intervention for symptomatic PAOD and carries a Class I, Level A recommendation. 1, 2

• Walking exercise should be performed at least 3 times per week, for a minimum of 30 minutes per session, for at least 12 weeks. 1
• High-intensity walking training (77-95% of maximal heart rate or 14-17 on Borg's scale) improves walking performance and cardiorespiratory fitness more effectively than lower intensities. 1
• Exercise training to moderate-severe claudication pain may be considered, though improvements are achievable with lesser pain severities. 1
• When SET is not available or feasible, structured and monitored home-based exercise training (HBET) with calls, logbooks, or connected devices should be considered as an alternative. 1

The 2025 ACR guidelines confirm that SET demonstrates superior outcomes compared to primary revascularization for intermittent claudication. 1

Lipid-Lowering Therapy

All patients with PAOD require statin therapy regardless of baseline lipid levels (Class I, Level A). 1

• Target LDL-C <1.4 mmol/L (55 mg/dL) with >50% reduction from baseline. 1
• If target not achieved on maximally tolerated statin, add ezetimibe. 1
• If target still not achieved on statin plus ezetimibe, add a PCSK9 inhibitor. 1
• For statin-intolerant patients at high cardiovascular risk not achieving LDL-C goals on ezetimibe, add bempedoic acid alone or with a PCSK9 inhibitor. 1
• Fibrates are not recommended for cholesterol lowering (Class III, Level B). 1

Antiplatelet Therapy

Antiplatelet monotherapy with either aspirin (75-160 mg daily) or clopidogrel (75 mg daily) is recommended for reduction of major adverse cardiovascular events (MACE) in symptomatic PAOD (Class I recommendation). 1, 2

• Clopidogrel is FDA-approved to reduce the rate of MI and stroke in patients with established peripheral arterial disease. 3
• Long-term dual antiplatelet therapy (DAPT) is not recommended in stable PAOD. 1
• Combination rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg daily) should be considered for patients with high ischemic risk and non-high bleeding risk. 1
• Oral anticoagulant monotherapy for PAOD (unless for another indication) is not recommended. 1
• Routine use of ticagrelor in PAOD patients is not recommended. 1

Additional Cardiovascular Risk Factor Management

Comprehensive risk factor modification is mandatory for all PAOD patients to reduce morbidity and mortality. 1

Diabetes Management

• Apply tight glycemic control (HbA1c <53 mmol/mol [7%]) to reduce microvascular complications. 1
• SGLT2 inhibitors with proven cardiovascular benefit are recommended in patients with type 2 diabetes and PAOD to reduce cardiovascular events. 1
• GLP-1 receptor agonists with proven cardiovascular benefit are recommended in patients with type 2 diabetes and PAOD to reduce cardiovascular events. 1
• Individualize HbA1c targets according to comorbidities, diabetes duration, and life expectancy. 1

Hypertension Management

• Target blood pressure control is recommended, though specific targets should be individualized. 1

Lifestyle Modifications

• Smoking cessation is essential and should be aggressively pursued. 4, 5
• Weight reduction for overweight/obese patients. 4

When to Consider Revascularization

Revascularization may only be considered after a 3-month period of OMT and exercise therapy in patients with symptomatic PAOD and impaired quality of life (QoL). 1

• PAD-related QoL assessment is recommended after the 3-month OMT trial. 1
• Revascularization is not recommended solely to prevent progression to chronic limb-threatening ischemia (CLTI). 1
• Revascularization is not recommended in asymptomatic PAOD. 1
• The mode and type of revascularization should be adapted to anatomical lesion location, lesion morphology, and general patient condition. 1

Diagnostic Workup

Duplex ultrasound (DUS) is the first-line imaging method to confirm PAOD lesions (Class I, Level C). 1

• In symptomatic patients with aorto-iliac or multisegmental/complex disease, CTA and/or MRA are recommended as adjuvant imaging for revascularization planning. 1
• Measure toe pressure (TP) or toe-brachial index (TBI) in patients with diabetes or renal failure if resting ankle-brachial index (ABI) is normal. 1

Follow-Up Strategy

Regular follow-up at least once yearly is recommended to assess clinical and functional status, medication adherence, limb symptoms, and cardiovascular risk factors, with DUS assessment as needed. 1

Common Pitfalls to Avoid

• Do not proceed directly to revascularization without a 3-month trial of OMT and SET—this approach leads to higher rates of secondary revascularization and increased 5-year mortality. 1
• Do not use long-term DAPT routinely—it increases bleeding risk without proven benefit in stable PAOD. 1
• Do not prescribe exercise training for patients with CLTI and wounds—it is contraindicated in this population. 1
• Do not use fibrates for cholesterol lowering—they are ineffective for this indication. 1