What is the recommended initial treatment approach for a patient with Peripheral Artery Occlusive Disease (PAOD)?

Initial Treatment Approach for Peripheral Artery Occlusive Disease (PAOD)

The initial treatment for PAOD must begin with comprehensive optimal medical therapy (OMT) including supervised exercise training, antiplatelet therapy, high-intensity statin therapy, blood pressure control, and smoking cessation—revascularization should only be considered after 3 months of OMT in patients with persistent lifestyle-limiting symptoms and impaired quality of life. 1, 2

First-Line Therapy: Supervised Exercise Training

• Supervised exercise training (SET) is the cornerstone of initial PAOD treatment and must be prescribed before considering any revascularization. 1, 2
• Exercise sessions should be performed at least 3 times per week, for at least 30 minutes per session, for a minimum of 12 weeks. 1, 3
• Walking should be the first-line training modality, performed at high intensity (77-95% of maximal heart rate or 14-17 on Borg's scale) to improve walking performance and cardiorespiratory fitness. 1, 2
• When SET is not available, structured and monitored home-based exercise training (HBET) with calls, logbooks, or connected devices should be considered. 1
• Patients should exercise to moderate-severe claudication pain to maximize walking performance improvements, though lesser pain severities can also yield benefits. 1

Antiplatelet Therapy

• Clopidogrel 75 mg daily is the preferred antiplatelet agent to reduce myocardial infarction, stroke, and vascular death in symptomatic PAOD patients. 2, 3, 4
• Aspirin 75-100 mg daily is an acceptable alternative for patients who cannot tolerate clopidogrel. 2, 3
• 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 to further reduce both cardiovascular and limb events. 1, 2, 5
• This combination therapy is also recommended following lower-limb revascularization in patients with non-high bleeding risk. 1
• Long-term dual antiplatelet therapy (aspirin plus clopidogrel) is NOT recommended for PAOD alone. 2

Lipid Management

• High-intensity statin therapy must be initiated immediately upon PAOD diagnosis, regardless of baseline cholesterol levels. 2, 5
• Target LDL-C <100 mg/dL (<2.6 mmol/L), and <70 mg/dL (<1.8 mmol/L or 1.4 mmol/L) for very high-risk patients with >50% reduction from baseline. 2, 5
• For statin-intolerant patients, add bempedoic acid alone or combined with a PCSK9 inhibitor. 2
• Fibrates are NOT recommended for cholesterol lowering in PAOD 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. 2, 3
• The European Society of Cardiology recommends targeting systolic blood pressure of 120-129 mmHg if tolerated. 5
• ACE inhibitors or ARBs are preferred antihypertensive agents due to their cardiovascular protection beyond blood pressure reduction. 2, 5
• Beta-blockers are NOT contraindicated in PAOD and are effective antihypertensive agents. 2

Diabetes Management

• Target HbA1c <7% (53 mmol/mol) to reduce microvascular complications in PAOD patients with diabetes. 2, 5
• SGLT2 inhibitors and GLP-1 receptor agonists with proven cardiovascular benefit should be prescribed to reduce cardiovascular events, independent of baseline HbA1c. 2, 5

Smoking Cessation

• Ask about tobacco use at every encounter, provide counseling, and develop a quit plan with pharmacotherapy for all PAOD patients who smoke. 2
• Offer one or more of: varenicline, bupropion, or nicotine replacement therapy, unless contraindicated. 2

Pharmacotherapy for Claudication Symptoms

• Cilostazol 100 mg twice daily should be prescribed for all patients with lifestyle-limiting claudication to improve walking distance, but is contraindicated in heart failure. 2
• Pentoxifylline may be considered as a second-line alternative to cilostazol, though its clinical effectiveness is marginal. 3, 6

When to Consider Revascularization

Revascularization should ONLY be considered after meeting ALL of the following criteria: 1, 2, 3

• 3-month trial of optimal medical therapy and supervised exercise therapy has been completed 1, 2
• Persistent lifestyle-limiting symptoms with impaired quality of life despite OMT 1, 2
• PAD-related quality of life assessment confirms significant disability affecting work or important activities 1
• Comprehensive risk factor modification and antiplatelet therapy already implemented 2
• Lesion anatomy with low procedural risk and high probability of initial and long-term success 2

Critical caveat: Revascularization is NOT recommended solely to prevent progression to chronic limb-threatening ischemia (CLTI), and is NOT recommended in asymptomatic PAOD. 1

Diagnostic Workup

• Ankle-brachial index (ABI) measurement is the primary diagnostic test for any patient with suspected PAOD. 1, 5
• Duplex ultrasound imaging of the aortoiliac segment/lower extremity should be obtained to determine concordance between clinical symptoms and PAD. 1
• Risk factor analysis including lipid profile should be performed at initial presentation. 1

Follow-Up Protocol

• Regular follow-up at least once annually is required to assess clinical and functional status, medication adherence, limb symptoms, and cardiovascular risk factors. 1, 2, 5
• Duplex ultrasound assessment should be performed as needed during follow-up. 1

Special Consideration: Acute Limb Ischemia (ALI)

If a patient presents with acute limb ischemia rather than chronic PAOD:

• Early anticoagulation is mandatory to limit thrombus propagation until definitive therapy can be employed. 1
• Cross-sectional imaging with CTA or MRA is recommended to reveal the exact nature and level of thrombosis. 1
• Expeditious catheter-directed mechanical thrombectomy or surgical revascularization is required to restore blood flow and limit irreversible tissue damage. 1

Special Consideration: Chronic Limb-Threatening Ischemia (CLTI)

• Early recognition of CLTI requires immediate referral to a vascular team for limb salvage. 1, 2
• Revascularization should be performed as soon as possible in CLTI patients. 2, 5
• Offloading mechanical tissue stress is indicated in patients with CLTI and ulcers to allow wound healing. 1
• Lower-limb exercise training is NOT recommended in patients with CLTI and wounds. 1