What is the next best lipid-lowering agent for a patient with elevated Low-Density Lipoprotein (LDL) levels, already on ezetimibe (10mg), and unable to take statins due to intolerance?

Next Lipid-Lowering Agent for Statin-Intolerant Patient on Ezetimibe 10mg with LDL 160 mg/dL

Add bempedoic acid to your current ezetimibe therapy as the next step, which will provide an additional 15-25% LDL-C reduction and has demonstrated cardiovascular outcomes benefit in statin-intolerant patients. 1

Treatment Algorithm Based on Cardiovascular Risk

For Very High-Risk Patients (established ASCVD, diabetes with target organ damage)

• Add bempedoic acid 180 mg daily to your current ezetimibe 10 mg, which will lower LDL-C by approximately 35% when combined 1
• Bempedoic acid demonstrated a 13% reduction in major adverse cardiovascular events (MACE) in the CLEAR Outcomes trial specifically in statin-intolerant patients 1
• The mechanism of action is upstream from statins in the liver, resulting in low rates of muscle-related adverse effects that make it particularly valuable for statin-intolerant patients 1
• If LDL-C remains ≥70 mg/dL after bempedoic acid + ezetimibe, add a PCSK9 inhibitor (evolocumab or alirocumab), which reduces LDL-C by approximately 50% 1

For High-Risk Patients (diabetes without ASCVD, 10-year ASCVD risk ≥7.5%)

• Add bempedoic acid 180 mg daily to current ezetimibe therapy 1
• Target LDL-C <100 mg/dL or at least 50% reduction from baseline 2
• Consider PCSK9 inhibitor only if LDL-C remains significantly elevated after bempedoic acid + ezetimibe combination 1

For Moderate-Risk Patients (10-year ASCVD risk <7.5%)

• Add bempedoic acid as the preferred next agent 1
• PCSK9 inhibitors do not have an established role for primary prevention in the absence of ASCVD or baseline LDL-C ≥190 mg/dL 2

Alternative Options (Less Preferred)

Bile Acid Sequestrants (BAS)

• May be considered if triglycerides are <300 mg/dL and patient cannot tolerate bempedoic acid 2
• Can provide modest hypoglycemic effect beneficial in diabetic patients 2
• Generally less preferred due to tolerability issues and lower efficacy compared to bempedoic acid 1

Higher-Dose Ezetimibe

• Ezetimibe 20 mg daily (off-label) produced additional 10.3% LDL-C reduction beyond the 10 mg dose in patients on statins 3
• This is not guideline-recommended but represents a potential option if other agents are unavailable or not tolerated 3

Monitoring Recommendations

• Monitor liver function tests when initiating bempedoic acid 1
• Reassess lipid profile in 4-8 weeks after adding bempedoic acid 1
• For patients on PCSK9 inhibitors, assess LDL-C response every 3-6 months 1
• Target LDL-C <70 mg/dL for very high-risk patients, <55 mg/dL for secondary prevention with very high cardiovascular risk 4

Important Clinical Considerations

Referral Indications

• Refer to lipid specialist if patient has complex mixed dyslipidemia, severe hypertriglyceridemia, or baseline LDL-C ≥190 mg/dL not due to secondary causes 2
• Consider referral if treatment goals not achieved on maximally tolerated combination therapy 4

Common Pitfalls to Avoid

• Do not use PCSK9 inhibitors as first-line after ezetimibe in primary prevention without trying bempedoic acid first, as PCSK9 inhibitors lack established role in this setting 2
• Do not overlook lifestyle modifications including weight loss, aerobic exercise, and dietary changes, which remain essential 4
• Avoid gemfibrozil if considering fibrate therapy; fenofibrate is preferred due to lower risk of muscle toxicity 4