Can atorvastatin be given to patients with elevated liver enzymes (hypertransaminasemia)?

From the Guidelines

Atorvastatin can be given to patients with elevated liver enzymes, but with caution and careful monitoring, especially in those with mild to moderate liver enzyme elevations (less than 3 times the upper limit of normal). When considering the use of atorvastatin in patients with elevated liver enzymes, it is essential to weigh the potential benefits of statin therapy against the risks of hepatotoxicity. According to the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1, statins can be used in patients with chronic, stable liver disease, including non-alcoholic fatty liver disease, after obtaining baseline measurements and determining a schedule of monitoring and safety checks. Key considerations include:

• Baseline liver function tests should be performed before starting atorvastatin, with follow-up testing recommended at 12 weeks after initiation or dose increase, and periodically thereafter 1.
• Patients with aspartate or alanine aminotransferase levels less than 3 times the normal levels do not warrant an immediate change in dose but should continue to follow up and consider repeated testing with their healthcare provider 1.
• Patients with aspartate and alanine aminotransferase levels greater than 3 times the normal levels should consult with their providers to evaluate the net benefit of continuing statin therapy versus adjusting or discontinuing medication 1.
• Routine measurements of creatine kinase and transaminase levels are not useful in patients treated with statins, except in cases of severe statin-associated muscle symptoms or recurrent statin-associated muscle symptoms despite appropriate statin rechallenge 1.

From the FDA Drug Label

Hepatic Dysfunction Inform patients that atorvastatin calcium tablets 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 use of atorvastatin in patients with elevated liver enzymes is not directly addressed in the provided drug label. However, it does mention that atorvastatin may cause liver enzyme elevations and possibly liver failure, and advises patients to report any symptoms that may indicate liver dysfunction.

• Key consideration: The label warns about the potential for liver enzyme elevations, which suggests caution when considering the use of atorvastatin in patients with pre-existing elevated liver enzymes.
• Clinical decision: Given the potential risk of exacerbating liver enzyme elevations, it would be prudent to exercise caution when prescribing atorvastatin to patients with elevated liver enzymes. 2

From the Research

Administration of Atorvastatin with Elevated Liver Enzymes

• Atorvastatin can be given to patients with elevated liver enzymes, as statins are essential medications for ischemic heart disease, stroke, and peripheral vascular disease, and have been proven to decrease mortality and morbidity 3.
• However, statins can cause transient elevation of liver enzymes in some patients, which may lead to unnecessary cessation of these agents prematurely 3.
• The elevations of liver function tests (LFTs) caused by statins are usually dose-dependent and borderline, and are clinically and statistically insignificant 4.
• A study found that patients using atorvastatin 40 mg/day had greater elevations of LFTs, but these elevations were almost always <2x the upper limit of normal (ULN) 4.
• The derangement in LFTs persisted and improvement was not seen, but this should not deter physicians from prescribing or continuing statins 4.

Evaluation of Elevated Liver Enzymes

• Elevated liver enzymes are a frequent finding in both symptomatic and asymptomatic patients, and necessitate further evaluation to clarify the underlying disease 5.
• The approach to elevated liver enzymes should be guided by both the clinical presentation and the pattern of injury 6.
• Clinicians can apply either an extensive testing strategy or a focused testing strategy to evaluate patients with elevated liver enzymes, and the choice of strategy depends on the pre-test probabilities and prior evaluations performed 7.
• Focused testing becomes the most cost-effective strategy when accounting for pre-test probabilities and prior evaluations performed, especially in the referral setting where assessments for viral hepatitis, alcoholic and non-alcoholic fatty liver disease have already been performed 7.