How often should liver function tests (LFT) be checked when on statin (HMG-CoA reductase inhibitor) therapy?

From the Guidelines

Liver function tests (LFTs) should be checked before starting statin therapy and as needed thereafter, with no routine periodic monitoring recommended for patients on stable statin therapy, as stated in the 2019 guideline 1. The frequency of checking LFTs in patients on statin therapy is a topic of debate, with various guidelines providing different recommendations. However, the most recent and highest quality study, the 2019 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol, suggests that routine measurements of creatine kinase and transaminase levels are not useful 1. Some key points to consider when checking LFTs in patients on statin therapy include:

• Checking LFTs before starting statin therapy to identify potential predisposing factors for statin-associated side effects 1
• Reassessing and rechallenging patients with statin-associated side effects that are not severe to achieve maximal LDL-C lowering 1
• Continuing statin therapy in patients with increased diabetes mellitus risk or new-onset diabetes mellitus, with added emphasis on adherence and net clinical benefit 1
• Measuring liver transaminases and total bilirubin and alkaline phosphatase if there are symptoms suggesting hepatotoxicity 1 It's also important to note that statin-induced liver injury is rare, occurring in less than 1% of patients, and that routine monitoring may not be effective in detecting or preventing this rare adverse effect 1. In terms of specific monitoring schedules, the 2016 ESC/EAS guidelines for the management of dyslipidaemias recommend checking liver enzymes before treatment, once 8-12 weeks after starting a drug treatment or after dose increase, and not routinely controlling ALT thereafter 1. Overall, the decision to check LFTs in patients on statin therapy should be based on individual patient factors and clinical judgment, rather than routine periodic monitoring.

From the Research

Liver Function Test (LFT) Monitoring on Statin Therapy

• The frequency of LFT monitoring for patients on statin therapy is a topic of discussion among healthcare professionals.
• According to a study published in 2020 2, statins can cause dose-dependent borderline elevations of liver function tests over time, but these elevations are clinically and statistically insignificant.
• A 2009 study 3 found that adherence to recommended laboratory monitoring for patients first prescribed with statin therapy is low, with over 90% of patients not following current recommendations.
• The American College of Cardiology and the American Heart Association do not provide specific guidelines on the frequency of LFT monitoring for patients on statin therapy.

Recommendations for LFT Monitoring

• A 2014 update by the Statin Liver Safety Task Force 4 suggests that regulatory agencies reconsider the statin-labeling recommendation, which required post-statin liver enzyme testing.
• 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.
• A 2009 study 5 recommends routine hepatic biochemical test monitoring, but the cost-effectiveness of this approach has been questioned.

Special Considerations

• Patients with nonalcoholic fatty liver disease (NAFLD) may benefit from statin therapy, as it can ameliorate liver histological and functional alterations 6.
• Statins are generally well tolerated in patients with chronic liver disease, such as NAFLD, primary biliary cirrhosis, and hepatitis C virus 5.
• However, decompensated cirrhosis and acute liver failure should be considered contraindications for lipid-lowering therapy 5.