Bempedoic Acid and Liver Enzyme Elevation
Yes, bempedoic acid can cause elevation in liver enzymes, and this is a recognized adverse effect that requires monitoring. 1
Evidence from Guidelines and FDA Labeling
The 2022 ACC Expert Consensus Decision Pathway explicitly lists elevated liver enzymes among the adverse effects of bempedoic acid in patients with primary hyperlipidemia and atherosclerotic cardiovascular disease (ASCVD). 1 This is documented in multiple sections of the guideline, confirming that hepatic transaminase elevations are an established side effect of this medication.
The FDA drug label does not specifically contraindicate bempedoic acid in patients with hepatic impairment, though it notes the drug was not studied in patients with severe hepatic impairment (Child-Pugh C). 2 This suggests the hepatotoxic potential is generally manageable but requires caution in advanced liver disease.
Clinical Significance and Frequency
The rate of elevated liver enzymes with bempedoic acid is increased compared to placebo, with an odds ratio of 4.28 (95% CI 1.34-13.71). 3 This meta-analysis of phase II and III trials demonstrates a statistically significant association between bempedoic acid treatment and hepatic enzyme elevation, though the absolute incidence remains relatively low.
In the CLEAR Outcomes trial involving 13,970 patients with established CVD or high CVD risk, abnormal liver function tests were among the adverse events that occurred at increased rates with bempedoic acid use. 1 This large cardiovascular outcomes trial provides robust real-world evidence of this adverse effect in the target patient population.
Monitoring Recommendations
While the guidelines do not mandate specific liver enzyme monitoring protocols for bempedoic acid (unlike statins or ezetimibe), clinical vigilance is warranted given the documented risk of hepatic transaminase elevations. 1
Practical monitoring approach:
- Obtain baseline liver function tests before initiating bempedoic acid 4
- Monitor liver enzymes as clinically indicated, particularly in the first few months of therapy 1
- Consider more frequent monitoring when combining bempedoic acid with statins or ezetimibe, as combination therapy may compound hepatic effects 4
- Discontinue or reduce dose if persistent ALT/AST elevations ≥3 times the upper limit of normal occur 4
Important Clinical Context
The liver enzyme elevations associated with bempedoic acid appear to be generally reversible and less severe than those seen with some other lipid-lowering agents. 3 The meta-analysis data suggests these elevations are manageable in most patients and do not typically require treatment discontinuation unless they become persistent or severe.
Bempedoic acid may actually have beneficial effects on hepatic steatosis through PPARα activation, 5 which distinguishes it from agents that worsen fatty liver disease. This mechanism suggests the transaminase elevations may not reflect progressive hepatotoxicity in most cases.
Key Caveats
- The increased risk of elevated liver enzymes should be weighed against bempedoic acid's favorable muscle safety profile, making it particularly valuable for statin-intolerant patients 6, 7
- Avoid use in patients with severe hepatic impairment (Child-Pugh C) due to lack of safety data 2
- The combination of bempedoic acid with ezetimibe (which also can elevate transaminases) requires careful monitoring 4
- Patients should be counseled to report symptoms of hepatic dysfunction (jaundice, dark urine, right upper quadrant pain) 1