What is the recommended use and dosage of bempedoic acid for adults with hyperlipidemia, particularly those with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease?

Bempedoic Acid for Hyperlipidemia

Bempedoic acid is indicated as adjunctive therapy to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL-cholesterol lowering, and it has proven cardiovascular benefit with a 13% reduction in major adverse cardiovascular events, particularly in statin-intolerant patients. 1, 2

Standard Dosing and Administration

The recommended dose is 180 mg orally once daily, with or without food, and the tablet should be swallowed whole. 3, 2

• This is a fixed dose that does not require adjustment based on LDL-C response 3
• When using the fixed-dose combination with ezetimibe, administer one tablet (180 mg bempedoic acid/10 mg ezetimibe) once daily 3
• If combining with bile acid sequestrants, take bempedoic acid either 2 hours before or 4 hours after the bile acid sequestrant 3

Clinical Indications and Treatment Positioning

Primary Indication: Statin-Intolerant Patients

Bempedoic acid is particularly valuable for statin-intolerant patients, as it reduces cardiovascular events by 13% compared with placebo and does not cause muscle-related side effects because it is only activated in the liver, not skeletal muscle. 1, 4, 5

• The CLEAR Outcomes trial demonstrated this cardiovascular benefit in 13,970 statin-intolerant patients with established ASCVD (70%) or high cardiovascular risk (30%) 1, 4
• Notably, the benefit was greater in primary prevention (HR 0.68,95% CI 0.53-0.87) compared to secondary prevention (HR 0.91,95% CI 0.81-1.01) 1
• Myalgia occurred in only 4.7% of bempedoic acid patients versus 7.2% with placebo 4

Treatment Hierarchy for Statin-Tolerant Patients

In patients who can tolerate statins, add ezetimibe first, then PCSK9 inhibitors (evolocumab or alirocumab) second, and reserve bempedoic acid as third-line therapy when additional LDL-C lowering is needed. 6

• However, in truly statin-intolerant patients, bempedoic acid moves to first-line therapy, followed by ezetimibe, then PCSK9 inhibitors 6, 4
• Before labeling a patient as statin-intolerant, confirm by attempting at least 2 different statins at varying doses 4

Efficacy Data

Bempedoic acid reduces LDL-cholesterol by approximately 21-24.5% as monotherapy and by 15-17.8% when added to existing statin therapy. 1, 4

• The fixed-dose combination of bempedoic acid 180 mg plus ezetimibe 10 mg achieves 38% additional LDL-C reduction when added to statin therapy 6, 4
• Bempedoic acid also reduces high-sensitivity C-reactive protein, suggesting anti-inflammatory effects 5, 7

Mechanism of Action

Bempedoic acid inhibits ATP-citrate lyase, an enzyme upstream of HMG-CoA reductase in the cholesterol synthesis pathway, resulting in upregulation of hepatic LDL receptors and improved LDL clearance. 4, 5

• The drug requires conversion to its CoA thioester for activation, which only occurs in the liver and not in skeletal muscle 5
• This hepatic-specific activation explains the absence of statin-associated muscle symptoms 4, 5

Critical Drug Interactions

Avoid concomitant use of bempedoic acid with simvastatin >20 mg daily or pravastatin >40 mg daily due to increased statin exposure risk. 3, 2

• These dose restrictions are mandatory to prevent adverse effects from elevated statin levels 3, 2

Safety Monitoring and Adverse Effects

Hyperuricemia and Gout

Bempedoic acid increases serum uric acid by a mean of 0.8 mg/dL, with gout occurring in 1.5% versus 0.4% with placebo. 3, 4, 2

• Assess uric acid levels before initiation and monitor periodically if symptoms of hyperuricemia occur 3, 2
• Initiate urate-lowering drugs as appropriate if hyperuricemia develops 2

Tendon Rupture

Tendon rupture occurred in 0.5% of patients versus 0% with placebo; discontinue bempedoic acid immediately at the first sign of tendon rupture. 6, 2

• Avoid bempedoic acid in patients with a history of tendon disorders or prior tendon rupture 2
• Counsel patients to report any tendon pain, swelling, or inflammation immediately 6

Other Monitoring Parameters

Monitor liver function tests at baseline and periodically as clinically indicated. 3, 4

• Other adverse effects include benign prostatic hyperplasia (1.3% vs 0.1%), atrial fibrillation (1.7% vs 1.1%), and creatine kinase elevation (1.0% vs 0.6%) 6
• Anemia and renal impairment occurred more frequently in the cardiovascular outcomes trial 2

Contraindications

Bempedoic acid is contraindicated in patients with a history of serious hypersensitivity reaction to bempedoic acid or any excipients. 2

Special Populations

Pregnancy and Lactation

Based on mechanism of action, bempedoic acid may cause fetal harm; breastfeeding is not recommended during treatment. 2

Access and Cost Considerations

Bempedoic acid is commercially available as a branded product that typically requires prior authorization from insurance plans, though patient assistance programs and discount copay cards are available for eligible patients. 6, 4

• The availability of fixed-dose combination bempedoic acid/ezetimibe may improve adherence in patients requiring multiple agents 6