Should statins (HMG-CoA reductase inhibitors) be discontinued in the presence of mild alanine transaminase (ALT) elevation?

From the Guidelines

You should not automatically stop statins due to mild ALT (alanine aminotransferase) elevations, as the cardiovascular benefits of statins usually outweigh the risk of liver injury, which is quite rare (occurring in less than 1% of patients) 1. If your ALT is less than three times the upper limit of normal, it's generally safe to continue your statin medication while monitoring liver function tests periodically. However, if ALT levels exceed three times the upper limit of normal, or if you experience symptoms like unusual fatigue, abdominal pain, dark urine, or yellowing of the skin or eyes, contact your healthcare provider immediately as these may indicate liver problems requiring statin discontinuation. Some key points to consider include:

• Mild ALT elevations on statins are relatively common and often transient, typically resolving even with continued therapy 1.
• Your doctor may recommend more frequent liver function monitoring or possibly switching to a different statin that might cause less elevation 1.
• Never stop your statin without consulting your healthcare provider, as abrupt discontinuation could increase your cardiovascular risk 1. It's essential to weigh the benefits of statin therapy against the potential risks and to closely monitor patients with elevated ALT levels, as recommended by the 2016 ESC/EAS guidelines for the management of dyslipidaemias 1.

From the FDA Drug Label

5.3 Hepatic Dysfunction Increases in serum transaminases have been reported with use of pravastatin [see Adverse Reactions (6.1)]. In most cases, these changes appeared soon after initiation, were transient, were not accompanied by symptoms, and resolved or improved on continued therapy or after a brief interruption in therapy. Persistent increases to more than three times the ULN in serum transaminases have occurred in approximately 1% of patients receiving either pravastatin or placebo in clinical studies Marked persistent increases of hepatic transaminases have also occurred with pravastatin. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pravastatin. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury Consider liver enzyme testing before pravastatin initiation and when clinically indicated thereafter. Pravastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis [see Contraindications (4)]. If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue pravastatin.

The decision to discontinue statins in the presence of mild alanine transaminase (ALT) elevation should be based on clinical judgment.

• The FDA label does not provide a specific ALT threshold for discontinuation.
• However, it is recommended to consider liver enzyme testing before pravastatin initiation and when clinically indicated thereafter.
• If serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs, promptly discontinue pravastatin.
• In the absence of specific guidance on mild ALT elevation, a conservative approach would be to monitor liver enzymes closely and consider discontinuation or dose adjustment if the elevation persists or worsens 2.

From the Research

Statin Therapy and ALT Elevation

• The decision to discontinue statins in the presence of mild alanine transaminase (ALT) elevation should be based on the individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved 3.
• Derangement in liver function tests, including ALT elevation, is common with statin use, affecting up to 1% of patients, but the clinical significance of this is unknown 4.
• There is no clear evidence that statin therapy causes significant liver damage, and the benefits of statin therapy in reducing cardiovascular risk outweigh the potential risks 3, 4.

Management of Statin-Intolerant Patients

• Statin intolerance is reported in 5-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes 5.
• For patients who are statin-intolerant, non-statin therapy may be required, and therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored 6, 5.
• Clinicians should consider using several different strategies to identify a tolerable statin regimen, including different statin, dose, and/or dosing frequency 5.

Benefits and Risks of Statin Therapy

• Statin therapy reduces the risk of major vascular events by about one-quarter for each mmol/L reduction in LDL cholesterol during each year that it continues to be taken 3.
• The only serious adverse events that have been shown to be caused by long-term statin therapy are myopathy, new-onset diabetes mellitus, and probably haemorrhagic stroke 3.
• Statin therapy may cause symptomatic adverse events, such as muscle pain or weakness, in up to about 50-100 patients per 10,000 treated for 5 years, but most of these events are not actually caused by the statin 3, 7.