What is the initial treatment approach for patients with Peripheral Artery Disease (PAD) and mildly decreased Ankle-Brachial Indices (ABIs)?

Treatment for PAD with Mildly Decreased ABIs

For patients with PAD and mildly decreased ABIs (≤0.90), initiate comprehensive guideline-directed medical therapy (GDMT) including single antiplatelet therapy, high-intensity statin, antihypertensive therapy if indicated, smoking cessation, and structured exercise—revascularization is not indicated for asymptomatic or mildly symptomatic patients. 1

Risk Stratification by ABI Value

The interpretation of ABI determines treatment intensity 1, 2:

• ABI ≤0.90 (Abnormal): Confirms PAD diagnosis; warrants full GDMT 1, 2
• ABI 0.91-0.99 (Borderline): Uncertain benefit from antiplatelet therapy; consider exercise ABI testing if symptomatic 1, 2
• ABI >1.40 (Noncompressible): Requires alternative testing with toe-brachial index (TBI), as this indicates medial arterial calcification and cannot reliably diagnose PAD 2

Core Medical Therapy Components

Antiplatelet Therapy

Single antiplatelet therapy is the standard approach for patients with asymptomatic PAD (ABI ≤0.90) 1:

• Aspirin 75-100 mg daily OR Clopidogrel 75 mg daily are both Class I recommendations for symptomatic PAD 1, 3
• For asymptomatic PAD with ABI ≤0.90, single antiplatelet therapy is reasonable (Class IIa) to reduce risk of major adverse cardiovascular events (MACE) 1
• Clopidogrel may be preferred based on the CAPRIE trial showing superior outcomes in PAD patients specifically 1, 3
• For borderline ABI (0.91-0.99), the benefit of antiplatelet therapy is uncertain (Class IIb) 1

Dual antiplatelet therapy is NOT recommended for initial treatment of asymptomatic or mildly symptomatic PAD 1:

• The combination of aspirin plus clopidogrel does not provide established benefit for cardiovascular event reduction in stable PAD (Class IIb) 1
• Dual antiplatelet therapy increases bleeding risk without proven benefit unless post-revascularization 1

Lipid-Lowering Therapy

High-intensity statin therapy is mandatory for all patients with PAD regardless of symptoms 1:

• Statin therapy is a Class I recommendation for all PAD patients to reduce cardiovascular events 1
• The 2024 guidelines strengthen this recommendation, emphasizing high-intensity statins specifically 1
• If LDL-C remains ≥70 mg/dL on maximally tolerated statin, adding ezetimibe or PCSK9 inhibitor therapy is reasonable (Class IIa) 1

Antihypertensive Therapy

Blood pressure control is essential for reducing cardiovascular events 1:

• Antihypertensive therapy should be administered to hypertensive PAD patients (Class I) 1
• ACE inhibitors or ARBs are preferred as they can be effective to reduce cardiovascular ischemic events in PAD patients (Class IIa) 1

Smoking Cessation

Smoking cessation is vital and should be addressed at every visit 1:

• Patients who smoke should be advised to quit at every visit (Class I) 1
• Assist with developing a cessation plan including pharmacotherapy (varenicline, bupropion, or nicotine replacement) and/or referral to cessation programs (Class I) 1

Exercise Therapy

Structured exercise is a cornerstone of treatment for PAD patients 1:

• Supervised exercise training is recommended as initial treatment for claudication (Class I) 1
• The program should involve intermittent walking to moderate-to-maximum claudication for 30-45 minutes per session, at least 3 times weekly for minimum 12 weeks 1
• The ERASE trial demonstrated that combination of endovascular revascularization plus supervised exercise was superior to exercise alone, but this applies to symptomatic patients with claudication, not asymptomatic or mildly symptomatic patients 1
• For asymptomatic or mildly symptomatic PAD, exercise therapy improves functional status without need for revascularization 1, 4

When Revascularization is NOT Indicated

Revascularization should NOT be performed in patients with asymptomatic PAD or mild symptoms 1:

• The IRONIC trial showed that at 5 years, revascularization plus optimal medical therapy had no long-term improvement in quality of life or walking capacity compared to medical therapy alone 1
• Invasive and noninvasive angiography should not be performed for anatomic assessment in asymptomatic PAD patients (Class III) 1, 2
• Revascularization is reserved for lifestyle-limiting claudication refractory to medical therapy and exercise, or for critical limb-threatening ischemia 1

Additional Pharmacotherapy for Symptomatic Patients

If patients develop refractory claudication despite exercise and medical therapy 1:

• Cilostazol 100 mg twice daily can be added to single antiplatelet therapy (Class IIa for symptomatic improvement) 1
• Cilostazol is contraindicated in heart failure patients 1
• Side effects include headache, diarrhea, dizziness, and palpitations, with 20% discontinuation rate 1

Common Pitfalls to Avoid

Do not use oral anticoagulation alone for PAD—it should not be used to reduce cardiovascular ischemic events (Class III: Harm) 1:

• Anticoagulation does not improve outcomes and increases bleeding risk 1

Do not routinely use dual antiplatelet therapy in stable PAD without revascularization 1:

• This increases bleeding risk without proven cardiovascular benefit 1

Do not omit statin therapy—PAD patients are undertreated compared to coronary artery disease patients despite similar cardiovascular risk 1:

• All PAD patients require statin therapy regardless of baseline LDL levels 1

Do not screen low-risk patients without risk factors or symptoms 2:

• ABI testing is not appropriate in patients <50 years without risk factors, as PAD prevalence is only ~1% in this population 2