What is the recommended treatment plan for a patient diagnosed with peripheral arterial disease (PAD)?

Recommended Treatment Plan for Peripheral Arterial Disease

All patients with PAD should receive a comprehensive treatment strategy consisting of supervised exercise therapy (at least 3 times weekly for 30+ minutes over 12 weeks), antiplatelet therapy (clopidogrel 75 mg daily preferred over aspirin), high-intensity statin therapy targeting LDL-C <55 mg/dL, blood pressure control to 120-129 mmHg systolic, smoking cessation with pharmacotherapy, and diabetes management with SGLT2 inhibitors or GLP-1 receptor agonists when applicable—with revascularization reserved only for patients with persistent lifestyle-limiting symptoms after 3 months of optimal medical therapy. 1, 2, 3

Initial Management Framework

Supervised Exercise Training (First-Line Therapy)

• Implement supervised exercise training (SET) as the cornerstone of PAD treatment with walking to moderate-severe claudication pain (77-95% maximal heart rate or 14-17 on Borg scale) 1, 2
• Exercise sessions must be at least 30 minutes duration, performed at least 3 times per week, for a minimum of 12 weeks 1, 3
• High-intensity walking training should be prioritized to improve both walking performance and cardiorespiratory fitness 1
• Alternative exercise modes (strength training, arm cranking, cycling, or combinations) can be considered as adjuncts 1
• Progressive increase in exercise training load every 1-2 weeks based on patient tolerance 1

Antiplatelet Therapy

• Clopidogrel 75 mg daily is the preferred antiplatelet agent for symptomatic PAD patients to reduce myocardial infarction, stroke, and vascular death 1, 2, 3
• Aspirin 75-100 mg daily is an acceptable alternative to clopidogrel 1, 2
• For 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 1
• This combination therapy should also be considered following lower-limb revascularization in patients with non-high bleeding risk 1
• Long-term dual antiplatelet therapy (DAPT) is NOT recommended 1
• For asymptomatic PAD with diabetes, aspirin 75-100 mg may be considered for primary prevention absent contraindications 1

Lipid Management

• High-intensity statin therapy is mandatory for all PAD patients targeting LDL-C <55 mg/dL (<1.4 mmol/L) with ≥50% reduction from baseline 1, 3
• For patients not achieving LDL-C goals on maximally tolerated statin, add ezetimibe 1
• For statin-intolerant patients at high cardiovascular risk not achieving goals on ezetimibe, add bempedoic acid alone or combined with a PCSK9 inhibitor 1
• Fibrates are NOT recommended for cholesterol lowering 1

Blood Pressure Management

• Target systolic blood pressure 120-129 mmHg 3
• Antihypertensive therapy should achieve <140/90 mmHg in patients without diabetes, or <130/80 mmHg in those with diabetes or chronic kidney disease 1
• Beta-blockers are effective antihypertensive agents and are NOT contraindicated in PAD 1
• ACE inhibitors may be considered for asymptomatic PAD to reduce adverse cardiovascular events 1
• Avoid dual RAS blockade (ACE inhibitor plus ARB) 3

Diabetes Management

• SGLT2 inhibitors with proven cardiovascular benefit are recommended for patients with type 2 diabetes and PAD to reduce cardiovascular events, independent of baseline HbA1c 1
• GLP-1 receptor agonists with proven cardiovascular benefit are recommended for patients with type 2 diabetes and PAD to reduce cardiovascular events 1
• Target HbA1c <53 mmol/mol (7%) to reduce microvascular complications 1
• Individualize HbA1c targets based on comorbidities, diabetes duration, and life expectancy 1
• Avoid hypoglycemia 1
• Prioritize glucose-lowering agents with proven cardiovascular benefits over those without 1
• Proper foot care is essential: appropriate footwear, daily foot inspection, skin cleansing, topical moisturizing creams, with urgent attention to skin lesions and ulcerations 1

Smoking Cessation

• Ask about tobacco use status at every visit 1
• Provide counseling and develop a quit plan with pharmacotherapy and/or referral to cessation programs 1
• Offer one or more of the following pharmacological therapies absent contraindications: varenicline, bupropion, or nicotine replacement therapy 1

Pharmacological Adjuncts for Claudication Symptoms

• Cilostazol 100 mg twice daily can be considered as adjunctive therapy to improve walking distance if exercise therapy alone is insufficient, though 20% of patients discontinue within 3 months due to side effects 2, 3
• Pentoxifylline may be considered as a second-line alternative to cilostazol, though its clinical effectiveness is marginal 2
• Note that pentoxifylline requires monitoring for bleeding risk, especially with concomitant NSAIDs, anticoagulants, or antiplatelet agents, and increased prothrombin time monitoring for patients on warfarin 4

Revascularization Decision-Making

When to Consider Revascularization

• 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, 2, 3
• After 3 months of OMT and exercise therapy, perform PAD-related quality of life assessment 1
• Adapt the mode and type of revascularization to anatomical lesion location, lesion morphology, and general patient condition 1

When NOT to Revascularize

• Revascularization is NOT recommended for asymptomatic PAD 1
• Revascularization is NOT recommended solely to prevent progression to chronic limb-threatening ischemia (CLTI) 1, 3

Revascularization Approach for Symptomatic PAD

• For femoro-popliteal lesions, drug-eluting treatment should be considered as first-choice strategy 1
• If revascularization is indicated for femoro-popliteal lesions, open surgical approach with autologous vein (e.g., great saphenous vein) should be considered in patients with low surgical risk 1
• In patients with severe intermittent claudication undergoing endovascular femoro-popliteal revascularization, treatment of below-the-knee arteries may be considered in the same intervention 1

Special Considerations for Chronic Limb-Threatening Ischemia (CLTI)

• Early recognition of CLTI and immediate referral to a vascular team are mandatory for limb salvage 1, 2
• Revascularization should be performed as soon as possible in CLTI patients 1
• CLTI patients must be managed by a vascular team 1
• For CLTI with ulcers, offloading mechanical tissue stress is required to allow wound healing 1
• Lower-limb exercise training is NOT recommended in CLTI patients with wounds 1
• Use autologous veins as the preferred conduit for infra-inguinal bypass surgery 1
• In multilevel vascular disease, eliminate inflow obstructions when treating downstream lesions 1
• For CLTI patients with good autologous veins and low surgical risk (<5% peri-operative mortality, >50% 2-year survival), infra-inguinal bypass may be considered 1
• Endovascular treatment may be considered as first-line therapy in CLTI patients with increased surgical risk or inadequate autologous veins 1

Diagnostic Considerations

• Duplex ultrasound (DUS) is the first-line imaging method to confirm PAD lesions 1
• In symptomatic patients with aorto-iliac or multisegmental/complex disease, CTA and/or MRA are recommended as adjuvant imaging techniques for revascularization preparation 1
• For patients with diabetes or renal failure, measure toe pressure (TP) or toe-brachial index (TBI) if resting ankle-brachial index (ABI) is normal 1
• Analyze anatomical imaging tests in conjunction with symptoms and hemodynamic tests prior to invasive procedures 1

Follow-Up Strategy

• Regular follow-up at least once annually is mandatory to assess clinical and functional status, medication adherence, limb symptoms, and cardiovascular risk factors, with duplex ultrasound assessment as needed 1, 2, 3
• Following CLTI revascularization, regular follow-up is required to assess clinical, hemodynamic and functional status, limb symptoms, treatment adherence, and cardiovascular risk factors 1

Common Pitfalls to Avoid

• Do not proceed directly to revascularization without the mandatory 3-month trial of optimal medical therapy and supervised exercise 1, 2, 3
• Do not use long-term DAPT routinely in PAD patients 1
• Do not use oral anticoagulant monotherapy for PAD unless indicated for another condition 1
• Do not routinely use ticagrelor in PAD patients 1
• Do not systematically treat asymptomatic PAD patients without clinically relevant atherosclerotic cardiovascular disease with antiplatelet drugs 1
• Do not use fibrates for cholesterol lowering 1
• Monitor for bleeding when using pentoxifylline, particularly with concomitant anticoagulants or antiplatelet agents 4
• Monitor theophylline levels when starting pentoxifylline or changing dose due to potential toxicity 4