Is bempedoic acid indicated for patients with elevated low-density lipoprotein cholesterol (LDL-C) levels?

Bempedoic Acid for Elevated LDL-C: Indications and Clinical Use

Yes, bempedoic acid is FDA-approved and indicated for patients with elevated LDL-C who have heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic cardiovascular disease (ASCVD) and require additional LDL-C lowering beyond maximally tolerated statin therapy. 1

FDA-Approved Indications

Bempedoic acid received FDA approval in 2020 with specific indications: 1

• As adjunct to diet and maximally tolerated statin therapy for adults with HeFH or ASCVD who require additional LDL-C lowering 1
• Available as monotherapy (180 mg daily) or in fixed-dose combination with ezetimibe (180 mg/10 mg) 1

Treatment Hierarchy: When to Use Bempedoic Acid

The American College of Cardiology establishes a clear algorithmic approach for nonstatin therapy sequencing: 1, 2

First-Line Nonstatin Agent

• Add ezetimibe first when maximally tolerated statin therapy fails to achieve LDL-C goals (provides ~18% additional LDL-C reduction as monotherapy, ~25% with statins) 2

Second-Line Nonstatin Agent

• Add PCSK9 monoclonal antibody (evolocumab or alirocumab) if LDL-C remains ≥70 mg/dL or <50% reduction despite statin plus ezetimibe (provides 40-65% additional LDL-C reduction with proven cardiovascular outcomes) 1, 2

Third-Line Nonstatin Agent

• Add bempedoic acid if LDL-C remains elevated (<50% reduction or LDL-C ≥70 mg/dL) after ezetimibe and/or PCSK9 inhibitor, or if patient cannot tolerate these therapies 1, 2
• Provides approximately 15-17.8% additional LDL-C reduction when added to statin therapy 1, 2
• Provides approximately 24.5% LDL-C reduction as monotherapy in statin-intolerant patients 1

Critical Exception: Statin-Intolerant Patients

In patients with documented statin intolerance, bempedoic acid moves to first-line therapy, fundamentally changing the treatment hierarchy: 2

• Bempedoic acid is activated only in the liver by very-long-chain acyl-CoA synthetase-1, an enzyme absent in muscle cells 1, 3
• This mechanism avoids statin-associated muscle symptoms 1, 4
• The CLEAR Outcomes trial demonstrated 13% reduction in 4-component MACE in high-risk patients with statin intolerance 5
• In the primary prevention cohort with statin intolerance, bempedoic acid reduced 4-component MACE by 30% (HR 0.70,95% CI 0.55-0.89) 5

Specific Clinical Scenarios Favoring Bempedoic Acid

The American College of Cardiology identifies key considerations that favor bempedoic acid: 1

• Documented statin intolerance with muscle symptoms 1
• Intolerance to other nonstatin medications (ezetimibe or PCSK9 inhibitors) 1
• Patient preference for oral therapy over injectable medications 1
• Need for further LDL-C reduction of approximately 17% beyond current therapy 1

High-Risk Populations Requiring Aggressive LDL-C Lowering

For patients with ASCVD and baseline LDL-C ≥190 mg/dL requiring rapid, aggressive reduction: 1

• Consider simultaneous addition of two agents (ezetimibe plus PCSK9 inhibitor) to maximally tolerated statin 1
• The fixed-dose combination of bempedoic acid 180 mg plus ezetimibe 10 mg provides 38% additional LDL-C reduction when added to statin therapy 1, 2

Cardiovascular Outcomes Evidence

The CLEAR Outcomes trial (completed in 2023, after the 2022 guideline publication) demonstrated: 5

• 13% reduction in 4-component MACE (HR 0.87,95% CI 0.79-0.96) 5
• 15% reduction in 3-component MACE 5
• 23% reduction in myocardial infarction 5
• 19% reduction in coronary revascularization 5
• Enrolled 14,014 high-risk patients with statin intolerance and LDL-C ≥100 mg/dL 1, 5

Critical Safety Considerations and Contraindications

Use bempedoic acid with caution in patients with: 1

• History of gout (increases uric acid by mean 0.8 mg/dL; gout occurred in 1.5% vs 0.4% placebo) 1, 6, 2
• History of tendon rupture (tendon rupture occurred in 0.5% vs 0% placebo) 1, 6, 2
• Monitor for benign prostatic hyperplasia (1.3% vs 0.1%), atrial fibrillation (1.7% vs 1.1%), and creatine kinase elevation (1.0% vs 0.6%) 1, 2

Dosing and Drug Interactions

Standard dosing: 6

• 180 mg orally once daily with or without food 6
• Fixed-dose combination: one tablet (180 mg bempedoic acid/10 mg ezetimibe) once daily 6

Critical drug interactions requiring dose limitations: 6

• Avoid simvastatin >20 mg daily due to increased exposure risk 6
• Avoid pravastatin >40 mg daily due to increased exposure risk 6
• Take 2 hours before or 4 hours after bile acid sequestrants 6

Practical Implementation Considerations

Cost and access barriers: 1, 2

• Bempedoic acid is commercially available as branded product only 1, 2
• Prior authorization typically required 2
• Patient assistance programs and discount copay cards available for eligible patients 1, 2
• Fixed-dose combination with ezetimibe may improve adherence in patients requiring multiple agents 1, 2

When to Refer to Lipid Specialist

Refer to lipid specialist if: 1

• Patient has <50% reduction in LDL-C or LDL-C ≥70 mg/dL (or non-HDL-C ≥100 mg/dL) despite combination statin and nonstatin therapy with ezetimibe, PCSK9 inhibitor, and/or bempedoic acid 1