Management of Peripheral Arterial Disease (PAD)
All patients with PAD require comprehensive cardiovascular risk reduction with antiplatelet therapy, high-intensity statin therapy, blood pressure control, smoking cessation, and supervised exercise training as first-line treatment, with revascularization reserved only for those with lifestyle-limiting symptoms persisting after 3 months of optimal medical therapy. 1, 2
Initial Assessment and Risk Stratification
Perform a systematic vascular assessment including:
- Detailed symptom review for walking impairment, claudication distance, ischemic rest pain, and nonhealing wounds 1, 3
- Comprehensive pulse examination of all lower extremity pulses with direct foot inspection (shoes and socks removed) 1, 3
- Bilateral arm blood pressure measurement to identify subclavian stenosis (>15-20 mmHg difference is significant) 3
- Ankle-brachial index (ABI) measurement as the initial diagnostic test (ABI ≤0.90 confirms PAD) 3
- For patients with normal ABI but high clinical suspicion, obtain post-exercise ABI (>20% decrease is diagnostic) 3
- In patients with non-compressible vessels (ABI >1.40, common in diabetes), use toe-brachial index instead 3
Antiplatelet Therapy
Clopidogrel 75 mg daily is the preferred antiplatelet agent to reduce myocardial infarction, stroke, and vascular death in all symptomatic PAD patients 1, 3, 2, 4. Aspirin 75-100 mg daily is an acceptable alternative 2.
For high-risk patients with PAD and non-high bleeding risk, consider combination therapy with rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily to further reduce cardiovascular events 1, 2. This applies particularly to patients following lower-limb revascularization 1.
Dual antiplatelet therapy (aspirin plus clopidogrel) may be considered in symptomatic PAD patients at high cardiovascular risk who are not at increased bleeding risk, though this is not routinely recommended 1, 2.
Warfarin should NOT be added to antiplatelet therapy as it provides no benefit and increases major bleeding risk 1.
Lipid Management
Initiate high-intensity statin therapy immediately upon PAD diagnosis, regardless of baseline cholesterol levels 3, 2. Target LDL-C <100 mg/dL, and <70 mg/dL for very high-risk patients 2.
Blood Pressure Control
Target blood pressure <140/90 mmHg in most patients, or <130/80 mmHg in those with diabetes or chronic kidney disease 3, 2.
Beta-blockers are NOT contraindicated in PAD and are effective antihypertensive agents 3, 2. ACE inhibitors should be considered to reduce adverse cardiovascular events 2.
Diabetes Management
Target HbA1c <7% (53 mmol/mol) to reduce microvascular complications in PAD patients with diabetes 2. SGLT2 inhibitors and GLP-1 receptor agonists with proven cardiovascular benefit are recommended for patients with type 2 diabetes and PAD 2.
Smoking Cessation
Ask about tobacco use at every encounter, provide counseling, and develop a quit plan with pharmacotherapy for all PAD patients who smoke 2. Offer varenicline, bupropion, or nicotine replacement therapy unless contraindicated 2.
Exercise Therapy: First-Line Treatment for Claudication
Supervised exercise training (SET) is the initial treatment before considering revascularization for intermittent claudication 1, 3, 2. This is a Class I recommendation with Level A evidence.
Exercise prescription specifics:
- Frequency: At least 3 times per week 1, 2
- Duration: 30-60 minutes per session 1
- Program length: Minimum 12 weeks 1, 2
- Intensity: High-intensity exercise (77-95% of maximal heart rate or 14-17 on Borg's scale) improves walking performance and cardiorespiratory fitness most effectively 1
- Modality: Walking should be the first-line training modality 1, 2
- Pain level: Exercise to moderate-severe claudication pain improves walking performance, though improvements are also achievable with lesser pain severities 1
When SET is not available, structured and monitored home-based exercise training (HBET) should be considered, though it is inferior to supervised programs 1. Monitoring should include calls, logbooks, or connected devices 1.
For patients undergoing endovascular revascularization, SET is recommended as adjuvant therapy 1.
Pharmacotherapy for Claudication
Cilostazol 100 mg twice daily should be considered for all patients with lifestyle-limiting claudication (contraindicated in heart failure) 1, 3, 2. This is the most effective pharmacological agent for improving symptoms and walking distance 1, 3.
Pentoxifylline 400 mg three times daily may be considered as a second-line alternative to cilostazol, though its clinical effectiveness is marginal and not well established 1, 5.
Other agents (L-arginine, propionyl-L-carnitine, ginkgo biloba) have marginal or unestablished effectiveness 1. Chelation therapy is NOT indicated and may be harmful 1.
Revascularization Criteria
Revascularization should only be considered after a 3-month trial of optimal medical therapy and exercise therapy in patients with persistent lifestyle-limiting symptoms 1, 2.
Patients must meet ALL of the following criteria before revascularization:
- Completed supervised exercise therapy and pharmacotherapy with inadequate response 1, 2
- Significant disability affecting work or important activities 1, 2
- Already receiving comprehensive risk factor modification and antiplatelet therapy 1, 2
- Lesion anatomy with low procedural risk and high probability of initial and long-term success 1, 2
In patients with symptomatic PAD, assess PAD-related quality of life after the 3-month period of optimal medical therapy 1. Revascularization may be considered if quality of life remains impaired 1.
Revascularization is NOT recommended solely to prevent progression to critical limb-threatening ischemia (CLTI) 1. Revascularization is NOT recommended in asymptomatic PAD 1.
For femoro-popliteal lesions, drug-eluting treatment should be considered as the first-choice endovascular strategy 1. Open surgical approach with autologous vein should be considered in low surgical risk patients when great saphenous vein is available 1.
Critical Limb-Threatening Ischemia (CLTI) Management
Early recognition of CLTI and immediate referral to a vascular team are essential for limb salvage 1, 2.
Patients with CLTI should undergo expedited evaluation and treatment of factors that increase amputation risk 1. Revascularization is indicated and should be performed as soon as possible 1, 2.
Patients with CLI in whom open surgical repair is anticipated should undergo cardiovascular risk assessment 1.
Systemic antibiotics should be initiated promptly in patients with CLTI, skin ulcerations, and evidence of limb infection 1, 2.
Patients with CLTI and skin breakdown should be referred to healthcare providers with specialized wound care expertise 1.
In patients with CLTI and ulcers, offloading mechanical tissue stress is indicated to allow wound healing 1.
Patients at risk for CLTI (ABI <0.4 with diabetes, or any diabetes patient with known PAD) should undergo regular foot inspection 1.
Acute Limb Ischemia
Patients with acute limb ischemia and a salvageable extremity should undergo emergent evaluation defining the anatomic level of occlusion, leading to prompt endovascular or surgical revascularization 1.
Patients with acute limb ischemia and a nonviable extremity should NOT undergo vascular anatomy evaluation or revascularization attempts 1.
Follow-Up and Surveillance
Regular follow-up at least once annually is required to assess clinical and functional status, medication adherence, limb symptoms, and cardiovascular risk factors, with duplex ultrasound as needed 1, 3, 2.
Patients with prior history of CLI or who have undergone successful CLI treatment should be evaluated at least twice annually by a vascular specialist due to high recurrence risk 1, 3, 2.
Long-term patency of infrainguinal bypass grafts should be evaluated in a surveillance program including interval vascular history, resting ABIs, physical examination, and duplex ultrasound at regular intervals 1, 3.
Patients at risk for or who have been treated for CLI should receive verbal and written instructions regarding self-surveillance for potential recurrence 1.
Common Pitfalls to Avoid
Do not proceed directly to revascularization without first completing a 3-month trial of optimal medical therapy and supervised exercise training in patients with intermittent claudication 1, 2. This is a critical error that deprives patients of effective, lower-risk treatment.
Do not withhold beta-blockers in PAD patients based on outdated concerns about worsening claudication 3, 2. They are safe and effective antihypertensive agents in this population.
Do not use warfarin in addition to antiplatelet therapy without another clear indication, as it increases bleeding risk without cardiovascular benefit 1.
Do not prescribe cilostazol to patients with heart failure as it is contraindicated 1, 3, 2.
Do not delay referral to a vascular team in patients with CLTI, as early recognition and treatment are essential for limb salvage 1, 2.