What is the best treatment approach for a patient with Peripheral Artery Occlusive Disease (PAOD) and Chronic Limb-Threatening Ischemia (CLTI)?

Management of PAOD with CLTI

For patients with chronic limb-threatening ischemia (CLTI), immediate revascularization is indicated for limb salvage, with the choice between endovascular and open surgical approaches determined by anatomic location, lesion complexity, availability of autologous vein, and patient surgical risk. 1

Immediate Actions and Assessment

Early recognition and urgent referral to a vascular team is mandatory to improve limb salvage outcomes 1. The management pathway differs fundamentally from intermittent claudication—CLTI requires prompt intervention rather than a trial of conservative therapy 1.

Initial Clinical Evaluation

• Assess extremity pulses, capillary refill, skin quality/color/temperature, and evidence of tissue compromise 1
• Perform ankle-brachial index (ABI) and pulse volume recording, though standard ABI may be falsely elevated due to medial sclerosis in diabetes or chronic kidney disease 1, 2
• Use alternative hemodynamic criteria when ABI is unreliable: ankle pressure <50 mmHg, toe pressure <30 mmHg, or TcPO2 <30 mmHg 1
• Obtain cross-sectional imaging with CTA or MRA for anatomic localization and revascularization planning 1

Risk Stratification

Assessment of amputation risk is indicated in all CLTI patients 1. CLTI is defined by the presence of:

• Ischemic rest pain
• Non-healing lower-limb wound ≥2 weeks duration
• Lower-limb gangrene 1

Medical Management (Adjunctive to Revascularization)

Antiplatelet Therapy

• Single antiplatelet therapy with aspirin (75-325 mg daily) is recommended for all symptomatic PAD patients to reduce major adverse cardiac events 1
• Clopidogrel is an alternative for aspirin-intolerant patients 2
• Dual antiplatelet therapy may be reasonable following revascularization to reduce limb-related events 1

Additional Medical Therapy

• Statins are indicated for all PAD patients regardless of lipid profile 1
• Antihypertensives for patients with hypertension reduce risk of stroke, MI, heart failure, and cardiovascular death 1
• Optimal glycemic control is recommended in CLTI patients with diabetes 1
• Initiate systemic anticoagulation with unfractionated heparin immediately unless contraindicated 2

Critical pitfall: Oral anticoagulant monotherapy is not recommended unless there is another indication (e.g., atrial fibrillation) 2. Anticoagulation alone is not an initial treatment option for CLTI 1.

Revascularization Strategy

Infra-popliteal revascularization is indicated for limb salvage in CLTI 1. The mode and type of revascularization must be adapted to anatomic lesion location, lesion morphology, and general patient condition 1.

Anatomic-Based Approach

For iliac lesions:

• Balloon angioplasty with or without stenting in external iliac arteries, or primary stenting in common iliac arteries should be considered 1

For femoro-popliteal lesions:

• Drug-eluting treatment should be considered as first-choice endovascular strategy 1, 2
• Endovascular therapy should be considered as initial approach 1
• Open surgical approach with autologous vein (great saphenous vein) should be considered when available in patients with low surgical risk 1

For infra-popliteal/below-the-knee lesions:

• Bypass using the great saphenous vein is indicated (Class I, Level A recommendation) 1
• Angiography including foot runoff should be considered prior to revascularization 1
• Revascularization should target the ischemic tissues using the angiosome concept 1

Patient-Specific Considerations

For high-risk surgical patients:

• Initial percutaneous revascularization is preferred over surgical approaches in patients with cardiac ischemia, cardiomyopathy, congestive heart failure, severe lung disease, or renal failure 3
• Endovascular treatment may be considered as first-line therapy in patients with increased surgical risk or inadequate autologous veins 3

Critical distinction: Unlike intermittent claudication where supervised exercise therapy may be superior to revascularization 1, CLTI requires revascularization as soon as possible 3, 2. The 3-month trial of optimal medical therapy and exercise that applies to claudication does NOT apply to CLTI 1, 4.

Contraindications to Revascularization

Absolute contraindications:

• Nonviable limb with extensive necrosis beyond salvage potential—primary amputation should be considered after interdisciplinary team evaluation 4
• Significant necrosis of weight-bearing portions of the foot, uncorrectable flexion contracture, paresis of the extremity, refractory ischemic rest pain with no revascularization options, sepsis, or very limited life expectancy 2

Important caveat: Even in patients with severe comorbidities, the risk-benefit calculation favors revascularization in CLTI, unlike in claudication where risks may outweigh benefits 4. An evaluation for revascularization options must be performed by an interdisciplinary care team before amputation 4.

Amputation Considerations

Minor Amputation

• Often necessary to remove necrotic tissues (up to forefoot level) with minor consequences on mobility 1
• Revascularization is needed before amputation to improve wound healing 1
• Foot TcPO2 and toe pressure can delineate the amputation zone 1

Major Amputation

• Reserved for patients with extensive necrosis or infectious gangrene, non-ambulatory patients with severe comorbidities, or when revascularization has failed 1
• Infragenicular amputation should be preferred when possible, as the knee joint allows better mobility with prosthesis 1

Post-Revascularization Management

• Monitor closely for compartment syndrome after revascularization and treat with emergent fasciotomy if clinical evidence develops 3, 2
• Clinical assessment of limb perfusion and neurological status is necessary 3
• Regular follow-up at least once yearly for all PAD patients, assessing clinical and hemodynamic status, functional status, medication adherence, and cardiovascular risk factors 2

Critical pitfall: Stem cell/gene therapy is not indicated in CLTI patients (Class III, Level B recommendation) 1. Despite ongoing investigation, there is insufficient evidence favoring these treatments 1.