Bempedoic Acid and Elevated Liver Function Tests
Bempedoic acid is NOT contraindicated in patients with elevated liver function tests. 1
Contraindications
The 2022 ACC Expert Consensus explicitly states that bempedoic acid has "Contraindication: none" in its prescribing information. 1 This is a critical distinction from many other lipid-lowering agents that carry hepatic contraindications.
Adverse Effects Related to Liver Function
While not contraindicated, elevated liver enzymes are listed as a known adverse effect of bempedoic acid therapy. 1 The 2025 ACC/AHA guideline specifically notes that in the CLEAR Outcomes trial, rates of abnormal liver function tests were increased with bempedoic acid use. 1
Clinical Monitoring Recommendations
- Monitor liver function tests as clinically indicated during treatment, though no specific baseline or routine monitoring schedule is mandated. 2
- The American College of Cardiology recommends monitoring liver enzymes but does not require discontinuation for mild elevations. 2
Pharmacokinetic Considerations in Hepatic Impairment
The FDA label provides important data on hepatic impairment: 3
- Mild hepatic impairment (Child-Pugh A): Bempedoic acid AUC decreased by 22% and Cmax by 11%
- Moderate hepatic impairment (Child-Pugh B): Bempedoic acid AUC decreased by 16% and Cmax by 14%
- Severe hepatic impairment (Child-Pugh C): Not studied
These reductions in exposure are not expected to result in lower efficacy and do not require dose adjustments. 3
Mechanism and Hepatic Activation
Bempedoic acid is a prodrug that requires hepatic activation by very-long-chain acyl-CoA synthetase-1 (ACSVL1), which is present in the liver but not skeletal muscle. 4, 5, 6 This liver-specific activation is the basis for its reduced muscle toxicity compared to statins. 4
Clinical Implications
- The hepatic activation mechanism means the drug requires functional liver tissue to be converted to its active form
- In patients with moderate hepatic impairment, the decreased exposure did not translate to reduced efficacy in clinical studies 3
- The absence of ACSVL1 in skeletal muscle explains the low rates of muscle-related adverse effects 7, 4
Practical Management Approach
For patients with baseline elevated LFTs:
- Bempedoic acid can be initiated without specific restrictions 1
- Assess the underlying cause of LFT elevation (e.g., NAFLD, alcohol, medications)
- Monitor LFTs as clinically indicated rather than on a fixed schedule 2
For patients who develop elevated LFTs on therapy:
- Mild elevations do not require discontinuation 1
- Consider other contributing factors (concomitant medications, disease progression)
- The drug can be continued with monitoring unless LFT elevations are severe or symptomatic
Important Caveats
- Severe hepatic impairment (Child-Pugh C) has not been studied, so use caution in this population 3
- Bempedoic acid may have beneficial effects on hepatic steatosis through PPARα activation, potentially improving fatty liver disease 8
- Unlike statins, there is no requirement for baseline LFT measurement before initiating therapy 1, 2