What is the best next step for a 63-year-old patient with asymptomatic Peripheral Artery Disease (PAD) taking aspirin (acetylsalicylic acid) 81 mg daily and atorvastatin (Lipitor) 80 mg daily with elevated Low-Density Lipoprotein Cholesterol (LDL-C) levels?

Management of Elevated LDL-C in a Patient with Asymptomatic PAD

Initiate ezetimibe since the patient's LDL-C is not at goal (<70 mg/dL). 1

Risk Assessment and Current Status

This 63-year-old patient with asymptomatic peripheral artery disease (PAD) is currently on:

• Aspirin 81 mg daily (appropriate antiplatelet therapy)
• Atorvastatin 80 mg daily (maximum dose high-intensity statin)
• Current LDL-C: 156 mg/dL

Guideline-Based Target LDL-C for PAD Patients

According to the 2019 ACC/AHA guidelines, patients with PAD are considered to have clinical atherosclerotic cardiovascular disease (ASCVD) and should target an LDL-C of <70 mg/dL, particularly if they have high-risk features 1.

PAD is explicitly listed as a form of clinical ASCVD in the guidelines, alongside coronary artery disease and cerebrovascular disease 1. The patient's current LDL-C of 156 mg/dL is significantly above the recommended target of <70 mg/dL, despite being on maximum-dose atorvastatin.

Treatment Algorithm

1. First-line therapy: High-intensity statin (patient is already on atorvastatin 80 mg)
2. If LDL-C remains ≥70 mg/dL on maximum statin: Add ezetimibe (Class IIa recommendation) 1
3. If LDL-C still ≥70 mg/dL after adding ezetimibe: Consider PCSK9 inhibitor (Class IIa recommendation) 1

Why Ezetimibe is the Correct Next Step

• The patient is already on maximum-dose statin therapy but has not achieved target LDL-C
• Ezetimibe is the recommended next agent to add when LDL-C remains ≥70 mg/dL despite maximally tolerated statin therapy 1
• Ezetimibe typically provides an additional 18-25% LDL-C reduction when added to statin therapy 2
• The IMPROVE-IT trial demonstrated that adding ezetimibe to statin therapy reduces cardiovascular events in high-risk patients 3

Why Other Options Are Incorrect

1. Initiating evolocumab: PCSK9 inhibitors should only be considered after ezetimibe has been added to maximally tolerated statin therapy and LDL-C still remains ≥70 mg/dL 1

2. Discontinuing atorvastatin: There is no evidence that atorvastatin contributes to claudication symptoms. In fact, high-dose statin therapy is recommended for all patients with PAD 4

3. No additional therapy needed: The statement that LDL-C <160 mg/dL is at goal is incorrect. For patients with clinical ASCVD including PAD, the target LDL-C is <70 mg/dL 1

Expected Benefits of Adding Ezetimibe

• Additional 18-25% reduction in LDL-C beyond statin therapy alone 2
• Improved cardiovascular outcomes as demonstrated in clinical trials 3
• Well-tolerated with minimal side effects 5
• Cost-effective compared to PCSK9 inhibitors as next-step therapy 6

Monitoring and Follow-up

• Check lipid panel 4-12 weeks after initiating ezetimibe
• If LDL-C remains ≥70 mg/dL despite ezetimibe addition, consider PCSK9 inhibitor therapy
• Continue to monitor for statin-associated side effects
• Emphasize adherence to both medications and lifestyle modifications

By following this evidence-based approach, you can optimize this patient's lipid management to reduce their risk of cardiovascular events associated with PAD.