What is the next plan for a patient with hyperlipidemia and coronary disease, previously on aspirin and statin therapy but discontinued due to gastrointestinal issues and pain, currently on Zetia (ezetimibe) with a recent low-density lipoprotein (LDL) cholesterol level of 105?

Intensify Lipid-Lowering Therapy Immediately with Bempedoic Acid

Add bempedoic acid 180 mg daily to the current ezetimibe regimen immediately, as this patient with established coronary artery disease and LDL-C of 105 mg/dL is far above the recommended target of <55 mg/dL for very high-risk patients. 1

Current Risk Assessment and Target LDL-C

• This patient has established atherosclerotic cardiovascular disease (ASCVD) with documented coronary stenosis, placing her in the very high-risk category 1
• Target LDL-C should be <55 mg/dL (<1.4 mmol/L) with at least a 50% reduction from baseline for patients with established coronary disease 1
• Current LDL-C of 105 mg/dL represents nearly double the recommended target, creating substantial residual cardiovascular risk 1

Addressing Statin Intolerance

• This patient meets criteria for statin intolerance (muscle pain leading to discontinuation), which requires alternative lipid-lowering strategies 1, 2
• Bempedoic acid is specifically indicated for statin-intolerant patients and demonstrated a 13% reduction in major adverse cardiovascular events (MACE) in the CLEAR Outcomes trial 1, 2
• Bempedoic acid provides 15-25% additional LDL-C reduction with minimal muscle-related adverse effects because it is activated only in the liver, not in skeletal muscle 1, 2

Recommended Treatment Algorithm

Step 1: Add Bempedoic Acid Now

• Initiate bempedoic acid 180 mg once daily in addition to current ezetimibe 10 mg 1, 2
• The combination of ezetimibe plus bempedoic acid can lower LDL-C by approximately 35% total 1, 2
• Monitor liver function tests at baseline and periodically, as bempedoic acid can cause elevations in hepatic enzymes 1
• Monitor uric acid levels, as bempedoic acid can increase uric acid and may precipitate gout in susceptible patients 1

Step 2: Reassess in 4-8 Weeks

• Recheck lipid panel in 4-8 weeks after initiating bempedoic acid 3, 4
• If LDL-C remains ≥70 mg/dL despite ezetimibe plus bempedoic acid, proceed to Step 3 1, 2

Step 3: Add PCSK9 Inhibitor if Needed

• Add a PCSK9 inhibitor (evolocumab, alirocumab, or inclisiran) if LDL-C target is not achieved with ezetimibe plus bempedoic acid 1, 3, 2
• PCSK9 inhibitors provide an additional 50-60% LDL-C reduction and are well-tolerated in statin-intolerant patients 3, 2
• These agents have demonstrated cardiovascular outcome benefits in patients with established ASCVD 1, 5

Addressing Aspirin Discontinuation

• Attempt to restart aspirin with gastroprotection (proton pump inhibitor) given her established coronary disease 6
• If aspirin remains absolutely contraindicated due to GI intolerance, consider clopidogrel 75 mg daily as an alternative antiplatelet agent for secondary prevention 6
• Antiplatelet therapy is essential for reducing recurrent cardiovascular events in patients with coronary artery disease 6

Critical Pitfalls to Avoid

• Do not delay intensification of lipid therapy – therapeutic inertia is a major contributor to suboptimal outcomes in high-risk patients 1
• Do not attempt statin rechallenge without addressing the pain issue first – this patient has already failed statin therapy due to pain, and forcing another trial without additional agents will likely fail 1, 2
• Do not accept LDL-C of 105 mg/dL as adequate – this level leaves substantial residual cardiovascular risk in a patient with established coronary disease 1
• Monitor for gout and gallstones with bempedoic acid, as these occurred at higher rates in clinical trials 1

Why This Approach Prioritizes Outcomes

• Lower LDL-C levels directly reduce cardiovascular mortality and morbidity – the relationship is linear with no apparent threshold, meaning "lower is better" even below 50 mg/dL 1, 5
• Combination therapy is necessary to achieve guideline-recommended targets in most very high-risk patients, particularly those who are statin-intolerant 1
• Bempedoic acid specifically addresses this patient's statin intolerance while providing proven cardiovascular benefit 1, 2