What to do next for a patient on statin (HMG-CoA reductase inhibitor) with elevated liver function tests (LFTs)?

From the Guidelines

For a patient on a statin with elevated liver function tests (LFTs), the first step is to determine the degree of elevation, and if the LFTs are less than 3 times the upper limit of normal (ULN), continue the statin but monitor LFTs more frequently, such as every 4-6 weeks, as recommended by the 2019 guideline 1. When managing a patient on statin therapy with elevated LFTs, it is crucial to balance the benefits of statin therapy in reducing cardiovascular risk with the potential risks of liver injury.

• The 2019 guideline suggests that in patients treated with statins, routine measurements of creatine kinase and transaminase levels are not useful 1, but it is essential to measure liver transaminases if there are symptoms suggesting hepatotoxicity.
• If LFTs are greater than 3 times ULN, temporarily discontinue the statin and recheck LFTs in 4-6 weeks, as elevated ALT levels (usually >1.5 or 2 times ULN) were excluded from RCT participation, and unexplained ALT ≥ 3 times ULN is a contraindication to statin therapy 1.
• Once LFTs normalize, consider restarting the same statin at a lower dose or switching to a different statin with less hepatic metabolism, such as rosuvastatin or pravastatin, as atorvastatin and simvastatin have more hepatic metabolism and may be more likely to cause LFT elevations.
• It is also important to note that mild, asymptomatic elevations in transaminases (up to 3 times ULN) are common with statins and often transient, occurring typically within the first few months of therapy, and usually do not indicate significant liver injury and rarely progress to liver failure.
• If the patient has symptoms of liver injury (jaundice, abdominal pain, fatigue), discontinue the statin immediately and perform a complete hepatic workup to rule out other causes of liver dysfunction, as recommended by the 2019 guideline 1.

From the FDA Drug Label

Hepatic Dysfunction Inform patients that rosuvastatin may cause liver enzyme elevations and possibly liver failure. Advise patients to promptly report fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice [see Warnings and Precautions (5. 3)] .

The patient should be advised to promptly report any symptoms of liver dysfunction, such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. However, the label does not provide specific guidance on what to do next for a patient on statin with elevated liver function tests (LFTs). Next steps are not explicitly stated in the label 2

From the Research

Next Steps for Patients on Statin with Elevated LFTs

• For patients with elevated liver function tests (LFTs) on statin therapy, the current evidence suggests that statin therapy should not be withheld 3.
• Patients with transaminase levels no more than three times the upper limit of normal can continue taking statins, as the elevations will often resolve spontaneously 4.
• The pattern of liver injury with statin use is not specific, and a correlation over time may not be apparent 5.
• Elevations of LFTs caused by statins are usually dose-dependent, borderline, and clinically insignificant, and should not deter physicians from prescribing or continuing statins 5.

Monitoring and Testing

• Current liver function testing for statin monitoring is largely unnecessary and costly, and statins do not cause liver disease 6.
• A single alanine transaminase (ALT) test rather than a full seven analyte liver function test (LFT) array may be sufficient for monitoring 6.
• Liver function tests should be ordered before starting statin therapy, 12 weeks after initiation, with any dose increase, and periodically for long-term maintenance therapy 7.

Considerations for Safe Use

• The risk of hepatic injury caused by statins is estimated to be about 1 percent, similar to that of patients taking a placebo 4.
• Coexisting elevations of transaminase levels from nonalcoholic fatty liver disease and stable hepatitis B and C viral infections are not contraindications to statin use 4.
• Clinically important drugs that interact with statins and increase the risk of adverse effects include fibrates, diltiazem, verapamil, and amiodarone 4.