What medications are used to treat Peripheral Artery Disease (PAD)?

Medications for Peripheral Artery Disease

For symptomatic PAD, start with single antiplatelet therapy using either aspirin 75-100 mg daily or clopidogrel 75 mg daily for cardiovascular event prevention, and add cilostazol 100 mg twice daily if claudication persists despite exercise therapy and smoking cessation. 1

Antiplatelet Therapy: The Foundation

For Symptomatic PAD (Established Disease)

• Single antiplatelet therapy is strongly recommended with either aspirin 75-100 mg daily OR clopidogrel 75 mg daily (Grade 1A recommendation). 1
• Clopidogrel may be preferred over aspirin, as the CAPRIE trial demonstrated a 24% significant reduction in vascular events compared to aspirin in PAD patients specifically. 2
• Avoid dual antiplatelet therapy (aspirin plus clopidogrel) in most PAD patients—it does not provide additional benefit over single therapy and increases major bleeding risk (Grade 2B). 1, 3
• Do not combine antiplatelet agents with warfarin in symptomatic PAD (Grade 1B). 1

For Asymptomatic PAD

• Consider aspirin 75-100 mg daily for primary prevention of cardiovascular events in patients ≥50 years old (Grade 2B), though the evidence is weaker than for symptomatic disease. 1

Newer Combination Therapy

• Rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily shows the strongest evidence for reducing both major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in symptomatic PAD, including benefits for total and cardiovascular mortality. 4, 3
• This combination represents the first antithrombotic regimen proven to reduce hard endpoints like total mortality in PAD patients. 3

Symptom Relief: Claudication Management

Cilostazol for Refractory Claudication

• Add cilostazol 100 mg twice daily to your baseline antiplatelet therapy (aspirin or clopidogrel) when claudication persists despite exercise therapy and smoking cessation (Grade 2C). 1
• This should only be considered after maximizing non-pharmacologic interventions—exercise rehabilitation programs are first-line. 1, 4

Avoid Pentoxifylline

• Do not use pentoxifylline for claudication—guidelines recommend against it (Grade 2C). 1
• Despite FDA approval, evidence does not support its efficacy compared to other options. 5

Critical Limb Ischemia

For Non-Revascularization Candidates

• Consider prostanoids in addition to baseline antiplatelet therapy for patients with critical limb ischemia and rest pain who cannot undergo revascularization (Grade 2C). 1
• Important caveat: Prostanoids have high likelihood of drug-related side effects, so only use in patients who value uncertain symptom relief over avoiding adverse effects. 1

Cardiovascular Risk Reduction Beyond Antiplatelets

Statin Therapy

• All PAD patients should receive statin therapy regardless of baseline cholesterol levels. 4
• Target LDL-C <70 mg/dL for very high-risk PAD patients. 4
• Statins reduce intermittent claudication incidence and improve exercise duration. 6

Blood Pressure Management

• Administer antihypertensive therapy to reduce MI, stroke, heart failure, and cardiovascular death risk. 4
• Target BP <140/90 mmHg (or <130/80 mmHg if diabetes or chronic kidney disease present). 4
• ACE inhibitors are specifically recommended for PAD patients. 6

Beta-Blockers

• Give beta-blockers if coronary artery disease is present—they do not worsen claudication symptoms contrary to historical concerns. 6

Post-Revascularization Management

After Peripheral Angioplasty/Stenting

• Continue long-term single antiplatelet therapy (aspirin 75-100 mg daily OR clopidogrel 75 mg daily) after percutaneous transluminal angioplasty with or without stenting (Grade 1A). 1
• Use single rather than dual antiplatelet therapy for stenting procedures (Grade 2C). 1
• Minimum 4 weeks of dual antiplatelet therapy may be considered for infrainguinal stent implantation, though single therapy is generally preferred. 3

After Bypass Surgery

• Continue aspirin 75-100 mg daily OR clopidogrel 75 mg daily long-term (Grade 1A). 1
• Exception: For below-knee bypass with prosthetic grafts, consider clopidogrel 75 mg plus aspirin 75-100 mg daily for 1 year (Grade 2C). 1
• Single antiplatelet therapy is preferred over combination with warfarin (Grade 1B). 1

Acute Limb Ischemia

• Immediate systemic anticoagulation with unfractionated heparin is recommended over no anticoagulation (Grade 2C). 1
• Surgery is preferred over intraarterial thrombolysis for definitive management (Grade 1B). 1

Critical Clinical Pitfalls

Common mistake: Using dual antiplatelet therapy routinely in stable PAD—this increases bleeding without cardiovascular benefit in most patients. The exception is the rivaroxaban-aspirin combination, which has proven mortality benefit. 1, 3

Aspirin efficacy controversy: While guidelines support aspirin, recent evidence suggests it may be less effective in PAD than in coronary disease, making clopidogrel a reasonable first choice. 7, 8

Sequencing error: Adding cilostazol before optimizing exercise therapy and smoking cessation—non-pharmacologic interventions must come first. 1, 4