Is liver function monitoring required after initiating statin (HMG-CoA reductase inhibitor) therapy?

From the Guidelines

Liver function monitoring is not required routinely after initiating statin therapy, but it is recommended to measure liver transaminases if there are symptoms suggesting hepatotoxicity. Specifically, the 2019 American College of Cardiology/American Heart Association guideline on the management of blood cholesterol recommends measuring liver transaminases (aspartate aminotransferase, alanine aminotransferase) as well as total bilirubin and alkaline phosphatase (hepatic panel) if there are symptoms suggesting hepatotoxicity 1. The guideline also states that routine measurements of creatine kinase and transaminase levels are not useful in patients treated with statins 1. Similarly, the 2016 European Society of Cardiology/European Atherosclerosis Society guidelines for the management of dyslipidaemias recommend monitoring liver enzymes (ALT) before treatment, once 8–12 weeks after starting a drug treatment or after dose increase, and routine control of ALT thereafter is not recommended during lipid-lowering treatment 1. However, the most recent and highest quality study, which is the 2019 American College of Cardiology/American Heart Association guideline, takes precedence. Key points to consider include:

• Performing a baseline liver function test before starting the statin is not explicitly recommended by the most recent guideline
• Repeat testing is only recommended if there are symptoms suggesting hepatotoxicity
• Key liver enzymes to monitor include ALT (alanine aminotransferase) and AST (aspartate aminotransferase)
• An elevation of these enzymes to more than 3 times the upper limit of normal is considered significant and may require dose adjustment or discontinuation of the statin. This approach prioritizes the patient's morbidity, mortality, and quality of life by avoiding unnecessary testing while still allowing for timely intervention in case of hepatotoxicity.

From the FDA Drug Label

Hepatic Dysfunction:Increases in serum transaminases have occurred, some persistent. Rare reports of fatal and non-fatal hepatic failure have occurred. Consider testing liver enzymes before initiating therapy and as clinically indicated thereafter. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue rosuvastatin tablets. ( 5.3)

Liver function monitoring is recommended after initiating statin (HMG-CoA reductase inhibitor) therapy, as increases in serum transaminases and rare reports of fatal and non-fatal hepatic failure have occurred. It is advised to consider testing liver enzymes before initiating therapy and as clinically indicated thereafter 2.

From the Research

Liver Function Monitoring after Initiating Statin Therapy

• Most studies do not recommend regular monitoring of liver function tests (LFTs) after starting statins unless clinically indicated 3, 4, 5.
• The Food and Drug Administration altered statin labeling such that unless clinically indicated for other reasons, after a pre-statin therapy baseline evaluation, follow-up liver enzyme testing was not uniformly required after statin initiation 5.
• Statin-induced liver injury is a well-recognized but rare phenomenon with hepatocellular, cholestatic, and mixed phenotypes 3.
• A study found that statins cause dose-dependent borderline elevations of liver function tests over time, but these elevations are clinically and statistically insignificant 6.

Exceptions to Routine Monitoring

• Patients with nonalcoholic fatty liver disease, potential drug interactions between statins and drugs used to treat hepatitis, liver transplant recipients, and patients with autoimmune liver disease may require closer monitoring 5.
• If liver enzymes are elevated at baseline, physicians may face a dilemma when determining if they should utilize statins, but existing literature provides guidance on the utilization of statins in these clinical scenarios 7.

Reduction of Unnecessary Liver Function Tests

• Reducing liver function tests for statin monitoring can be achieved by using a single alanine transaminase (ALT) rather than a full seven analyte liver function test (LFT) array, which can reduce cost and may benefit patients 4.
• An intervention to reduce full-array LFTs ordered by GPs for statin monitoring resulted in a significant reduction in the full LFT array per 1000 people on statins 4.