Lipid Management in Statin-Refusing Patients

Introduction to Alternative Therapies

The American College of Cardiology recommends adding bempedoic acid 180 mg daily to ezetimibe 10 mg for very high-risk patients, targeting LDL-C <55 mg/dL and ≥50% reduction from baseline 2, 1
Bempedoic acid demonstrates a 13% reduction in major adverse cardiovascular events (MACE) in statin-intolerant patients, as shown in the CLEAR Outcomes trial 1
The combination of bempedoic acid plus ezetimibe can lower LDL-C by approximately 35% total 1

For very high-risk patients, add a PCSK9 inhibitor (evolocumab or alirocumab preferred) if LDL-C remains ≥55 mg/dL after 4-12 weeks, for an additional ~50% LDL-C reduction 2, 3, 1
For high-risk patients, add bempedoic acid 180 mg daily to ezetimibe, targeting LDL-C <70 mg/dL and ≥50% reduction from baseline 3, 1
For moderate-risk patients, add bempedoic acid 180 mg daily to ezetimibe if LDL-C remains ≥100 mg/dL or non-HDL-C ≥130 mg/dL, targeting LDL-C <100 mg/dL or at least 30-49% reduction from baseline 4, 1

Bempedoic acid works upstream from statins in the cholesterol synthesis pathway, resulting in very low rates of muscle-related adverse effects, making it valuable for statin-refusing or statin-intolerant patients 1
Bempedoic acid is an oral medication with once-daily dosing, improving adherence compared to injectable PCSK9 inhibitors 1

The American College of Cardiology prefers PCSK9 inhibitors (evolocumab, alirocumab) over inclisiran as the initial PCSK9 inhibitor choice due to demonstrated cardiovascular outcomes benefits in the FOURIER and ODYSSEY Outcomes trials 2
PCSK9 inhibitors reduce LDL-C by approximately 50% and are well-tolerated in statin-intolerant patients 1

Bile acid sequestrants (colesevelam, cholestyramine) may be considered if triglycerides are <300 mg/dL and the patient cannot tolerate bempedoic acid, providing 15-30% LDL-C reduction 4, 1

Obtain lipid panel 4-8 weeks after adding any new agent to assess response, and monitor liver enzymes (ALT/AST) at baseline and periodically when using bempedoic acid 1

Refer patients with baseline LDL-C ≥190 mg/dL not due to secondary causes, complex mixed dyslipidemia, or severe hypertriglyceridemia (>500 mg/dL) to a lipid specialist 5, 1

Do not use PCSK9 inhibitors as first-line after ezetimibe in primary prevention without trying bempedoic acid first, as PCSK9 inhibitors lack an established role in this setting and are significantly more expensive 1
Reassess statin refusal, as alternative dosing regimens (every other day, twice weekly) may be tolerated 1