What is the recommended 2025 management for peripheral arterial disease, including cardiovascular risk reduction, pharmacologic therapy, supervised exercise, and revascularization?

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Management of Peripheral Arterial Disease (2025)

First-Line Treatment Strategy

All patients with PAD should receive comprehensive optimal medical therapy (OMT) combined with supervised exercise training (SET) as initial treatment; revascularization is reserved exclusively for those with persistent lifestyle-limiting symptoms after completing at least 3 months of this approach. 1

Cardiovascular Risk Reduction

Antiplatelet Therapy

  • Clopidogrel 75 mg once daily is the preferred antiplatelet agent for all symptomatic PAD patients to reduce myocardial infarction, stroke, and vascular death. 1

  • For high-risk PAD patients without high bleeding risk, combination therapy with rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily should be considered to further reduce cardiovascular events and major adverse limb events. 1

  • This dual-pathway inhibition (rivaroxaban + aspirin) should also be considered following lower-limb revascularization in patients without high bleeding risk. 1

  • Aspirin 75-100 mg daily is an acceptable alternative to clopidogrel monotherapy. 1

  • Dual antiplatelet therapy with aspirin plus clopidogrel is NOT routinely recommended for PAD alone, though it may be considered in very high-risk patients without increased bleeding risk. 1

  • Warfarin should never be added to antiplatelet therapy as it provides no cardiovascular benefit and significantly increases major bleeding risk. 1

Lipid Management

  • High-intensity statin therapy is mandatory immediately upon PAD diagnosis, regardless of baseline cholesterol levels, targeting LDL-C <55 mg/dL (<1.4 mmol/L) with ≥50% reduction from baseline. 2, 3

  • For patients unable to tolerate statins, add bempedoic acid alone or combined with a PCSK9 inhibitor. 2

Blood Pressure Control

  • Target blood pressure to 120-129 mmHg systolic in most PAD patients. 3

  • ACE inhibitors or angiotensin receptor blockers (ARBs) should be considered to reduce adverse cardiovascular events. 2, 4

  • Beta-blockers are NOT contraindicated in PAD and are effective antihypertensive agents. 2

Smoking Cessation

  • Smoking cessation is absolutely essential and should be addressed at every clinical encounter with counseling and pharmacotherapy (varenicline, bupropion, or nicotine replacement therapy). 2, 4

Diabetes Management

  • Target HbA1c <7% (53 mmol/mol) to reduce microvascular complications. 2

  • SGLT2 inhibitors and GLP-1 receptor agonists with proven cardiovascular benefit are recommended for patients with type 2 diabetes and PAD. 2

Supervised Exercise Training (SET)

SET carries a Class I, Level A recommendation and must be offered before any consideration of revascularization in symptomatic PAD. 1

Exercise Prescription Parameters

  • Frequency: Minimum 3 sessions per week 1

  • Duration: 30-60 minutes per session 1

  • Program length: Minimum 12 weeks 1

  • Intensity: High-intensity exercise (77-95% of maximal heart rate or 14-17 on Borg's perceived exertion scale) yields the greatest improvements in walking performance and cardiorespiratory fitness. 1

  • Modality: Walking is the first-line training activity, though alternative modes (strength training, arm cranking, cycling) should be considered when walking is not feasible. 1

  • Pain level: Exercise to moderate-severe claudication pain improves walking distance more effectively, though improvements are also achievable with lesser pain severities. 1

  • Training programs should begin at low-to-moderate intensity, gradually advancing to vigorous exercise if well tolerated. 1

When SET is Unavailable

  • Structured home-based exercise training (HBET) should be offered when SET is not available or feasible, though it is inferior to supervised programs. 1

  • HBET inferiority is reduced if monitoring is implemented via telephone calls, logbooks, or connected devices. 1

Post-Revascularization

  • SET is recommended as adjunctive therapy following endovascular revascularization to maintain and enhance functional gains. 1

Pharmacologic Therapy for Claudication

  • Cilostazol 100 mg twice daily should be considered for all patients with lifestyle-limiting claudication (contraindicated in heart failure) and is the most effective medication for improving symptoms and walking distance. 1, 2

  • Pentoxifylline 400 mg three times daily may be used as a second-line alternative, though its clinical benefit is marginal. 1

  • Other agents (L-arginine, propionyl-L-carnitine, ginkgo biloba) have only marginal or unestablished effectiveness. 1

Revascularization Decision Algorithm

Mandatory Prerequisites (ALL Must Be Met)

Revascularization should be considered ONLY after completing the following 3-month trial: 1, 3

  1. Completion of supervised exercise training (minimum 12 weeks, 3x/week, 30-60 minutes/session) 1

  2. Trial of optimal medical therapy including antiplatelet therapy, high-intensity statin, blood pressure control, and cilostazol if not contraindicated 1, 2

  3. After 3 months, formal assessment of PAD-related quality of life 1

Additional Criteria for Revascularization

All of the following must also be present: 1, 2

  • Persistent lifestyle-limiting symptoms with significant disability affecting work or important daily activities 1, 2

  • Impaired PAD-related quality of life despite optimal medical therapy and exercise 1

  • Ongoing comprehensive risk-factor modification and antiplatelet therapy 1

  • Lesion anatomy presenting low procedural risk with high probability of immediate and long-term technical success 1

Revascularization Strategy by Lesion Location

  • For femoro-popliteal lesions, drug-eluting endovascular therapy should be considered as the first-choice strategy. 1

  • Open surgical bypass using autologous vein (e.g., great saphenous vein) should be considered when available in patients with low surgical risk. 1

  • In patients with severe intermittent claudication undergoing endovascular femoro-popliteal revascularization, treatment of below-the-knee (BTK) arteries may be considered in the same intervention. 1

When Revascularization is NOT Indicated

  • Revascularization is NOT recommended solely to prevent progression to chronic limb-threatening ischemia (CLTI). 1

  • Revascularization is NOT recommended in asymptomatic PAD. 1

Chronic Limb-Threatening Ischemia (CLTI)

Recognition and Referral

  • Early recognition of CLTI and immediate referral to a vascular team are essential for limb salvage. 1

  • All CLTI patients must be managed by a multidisciplinary vascular team. 1

Medical Management

  • Revascularization should be performed as soon as possible in CLTI patients. 1

  • Systemic antibiotics should be started promptly in CLTI patients with skin ulcerations or evidence of infection. 2

  • Offloading mechanical tissue stress is indicated for CLTI-related ulcers to facilitate wound healing. 1

  • Lower-limb exercise training is NOT recommended in patients with CLTI and wounds. 1

Revascularization Strategy

  • In multilevel vascular disease, eliminate inflow obstructions when treating downstream lesions. 1

  • Autologous veins are the preferred conduit for infra-inguinal bypass surgery. 1

  • In 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, especially in patients with increased surgical risk or inadequate autologous veins. 1

Risk Assessment

  • Patients at risk for CLTI (e.g., ABI <0.4 with diabetes or any diabetic patient with known PAD) should undergo regular foot inspection. 2

Follow-Up and Surveillance

Routine PAD Follow-Up

  • All PAD patients require regular follow-up at least once annually to assess clinical and functional status, medication adherence, limb symptoms, and cardiovascular risk factors. 1

  • Duplex ultrasound assessment should be performed as needed. 1

Post-Revascularization Surveillance

  • Following revascularization, patients require regular follow-up with assessment of clinical, hemodynamic, and functional status. 1

  • Long-term patency of infra-inguinal bypass grafts should be monitored through a surveillance program including vascular history, resting ABI, physical examination, and periodic duplex ultrasound. 2

CLTI Follow-Up

  • Patients with a history of CLTI or successful CLTI treatment should be evaluated at least twice yearly by a vascular specialist due to high recurrence risk. 2

  • Patients at risk for or treated for CLTI should receive verbal and written instructions for self-surveillance of recurrence. 2

Critical Pitfalls to Avoid

  • Do NOT proceed directly to revascularization without completing a 3-month trial of optimal medical therapy and supervised exercise training in patients with intermittent claudication. 1, 3

  • Do NOT add warfarin to antiplatelet therapy without a clear indication, as it increases bleeding risk without cardiovascular benefit. 1

  • Do NOT prescribe cilostazol to patients with heart failure because it is absolutely contraindicated. 1, 2

  • Do NOT delay referral to a vascular team in patients with CLTI; early recognition and treatment are critical for limb salvage. 1

  • Do NOT perform revascularization solely to prevent progression to CLTI in asymptomatic or mildly symptomatic patients. 1

  • Do NOT underestimate the importance of supervised exercise training—it is as effective as revascularization for improving walking distance and quality of life in many patients with intermittent claudication. 1, 5

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Guideline

Comprehensive Management of Peripheral Arterial Disease (PAD)

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

3
Guideline

Peripheral Arterial Disease Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

5
Research

Exercise training and peripheral arterial disease.

Comprehensive Physiology, 2012

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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