What oral medications are recommended for an older adult patient with Peripheral Artery Disease (PAD), a history of smoking, diabetes, high blood pressure (hypertension), and high cholesterol (hyperlipidemia)?

Oral Medications for Peripheral Artery Disease

For an older adult with PAD, smoking history, diabetes, hypertension, and hyperlipidemia, you must prescribe: (1) clopidogrel 75 mg daily OR aspirin 75-325 mg daily for antiplatelet therapy, (2) high-intensity statin targeting LDL-C <55 mg/dL with ≥50% reduction from baseline, (3) ACE inhibitor or ARB for blood pressure control targeting 120-129 mmHg systolic, (4) SGLT2 inhibitor or GLP-1 receptor agonist with proven cardiovascular benefit for diabetes management, and (5) cilostazol 100 mg twice daily if claudication symptoms persist despite exercise therapy. 1, 2

Antiplatelet Therapy (Mandatory for All PAD Patients)

• Clopidogrel 75 mg daily is the preferred single antiplatelet agent based on the CAPRIE trial demonstrating 24% relative risk reduction in cardiovascular events compared to aspirin specifically in PAD patients 2, 3
• Aspirin 75-325 mg daily is an acceptable alternative if clopidogrel is contraindicated or unavailable 1, 2
• Single antiplatelet therapy reduces myocardial infarction, stroke, and vascular death—this is non-negotiable for symptomatic PAD 1, 4, 2
• Do NOT use dual antiplatelet therapy routinely as it increases major bleeding risk without additional cardiovascular benefit in stable PAD 2

Lipid-Lowering Therapy (Mandatory for All PAD Patients)

• High-intensity statin therapy is required for all PAD patients regardless of baseline cholesterol levels 1
• Target LDL-C <55 mg/dL (1.4 mmol/L) AND achieve ≥50% reduction from baseline 1
• If target not achieved on maximally tolerated statin, add ezetimibe 1
• If still not at goal on statin plus ezetimibe, add PCSK9 inhibitor 1
• For statin-intolerant patients at high cardiovascular risk not achieving LDL-C goal on ezetimibe, add bempedoic acid alone or combined with PCSK9 inhibitor 1
• Statins reduce cardiovascular death, MI, stroke, and improve walking distance in PAD patients 1, 5

Antihypertensive Therapy

• Target systolic blood pressure 120-129 mmHg if tolerated to reduce cardiovascular disease risk 1
• ACE inhibitors or ARBs are the preferred first-line agents for cardiovascular protection in PAD patients 1, 2
• ACE inhibitors reduce adverse cardiovascular events in symptomatic PAD patients (Class IIa recommendation) 1
• Beta-blockers are NOT contraindicated in PAD—they do not worsen walking distance or claudication symptoms and should be used if coronary artery disease or heart failure coexists 1
• Combination therapy with ACE inhibitors/ARBs plus diuretics and/or calcium channel blockers should be considered for difficult-to-control hypertension 1

Diabetes Management

• SGLT2 inhibitors with proven cardiovascular benefit are recommended to reduce cardiovascular events independent of baseline HbA1c 1
• GLP-1 receptor agonists with proven cardiovascular benefit are recommended to reduce cardiovascular events independent of baseline HbA1c 1
• Target HbA1c <7% (53 mmol/mol) to reduce microvascular complications 1
• Prioritize glucose-lowering agents with proven cardiovascular benefits over agents without proven cardiovascular benefit or safety 1
• Avoid hypoglycemia in PAD patients 1

Claudication Symptom Management

• Add cilostazol 100 mg twice daily if claudication persists despite exercise therapy and smoking cessation 1, 2, 6
• Cilostazol improves maximal walking distance by 40-60% after 12-24 weeks 2
• Critical caveat: Cilostazol does NOT reduce cardiovascular mortality or major cardiovascular events—patients still require clopidogrel or aspirin for mortality reduction 2
• Cilostazol is contraindicated in heart failure patients 1

Smoking Cessation Pharmacotherapy (If Currently Smoking)

• All smokers with PAD must be offered pharmacological therapy 2
• Varenicline, bupropion, and nicotine replacement therapy are equally effective options 2, 6
• Smoking cessation is the most important factor in preventing PAD progression 1

Critical Pitfalls to Avoid

• Never delay antiplatelet therapy—PAD patients are at very high cardiovascular risk with 25-35% one-year mortality if critical limb-threatening ischemia develops 4
• Do not use cilostazol as the sole antiplatelet agent—it does not reduce cardiovascular events and patients still need clopidogrel or aspirin 2
• Avoid combining antiplatelet agents with warfarin unless there is a specific indication for anticoagulation (e.g., atrial fibrillation) 2
• Do not withhold beta-blockers unnecessarily—they are safe and effective in PAD patients, especially with coexisting coronary disease 1
• Fibrates are NOT recommended for cholesterol lowering in PAD patients 1
• Antihypertensive drugs do not improve walking distance or claudication symptoms—their purpose is cardiovascular risk reduction 1