When should HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors, commonly referred to as statins, be discontinued?

From the Guidelines

Statins should be discontinued in patients who experience severe side effects, such as significant muscle symptoms with elevated creatine kinase (CK) levels greater than 10 times the upper limit of normal, rhabdomyolysis, or severe liver dysfunction with persistent elevations in liver enzymes (ALT/AST) greater than 3 times the upper limit of normal, as recommended by the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol 1.

When considering discontinuation of statins, it is essential to weigh the benefits of statin therapy against the risks of adverse effects. The decision to stop statins should be individualized and involve shared decision-making with the patient.

Some key points to consider when deciding to discontinue statins include:

• Severe muscle symptoms, such as those associated with rhabdomyolysis, warrant prompt discontinuation of statin therapy and evaluation for other causes of muscle symptoms 1.
• Patients who experience mild to moderate muscle symptoms may be able to tolerate a different statin or dosing regimen after a drug holiday, and rechallenge with a lower dose of a different statin may be considered 1.
• Statins should also be discontinued in patients who develop contraindications, such as pregnancy, active liver disease, or hypersensitivity reactions.
• In patients with limited life expectancy or those receiving palliative care, the benefits of statins may no longer outweigh the burdens, and discontinuation may be considered on a case-by-case basis.
• Temporary discontinuation may be appropriate during acute illness, major surgery, or when starting medications with significant interaction potential.

It is crucial to note that the benefits of statin therapy in reducing the risk of atherosclerotic cardiovascular disease (ASCVD) events often outweigh the risks of adverse effects, and discontinuation of statins should not be taken lightly. As stated in the 2019 guideline on the management of blood cholesterol, "the possibility of incident diabetes mellitus should not be a contraindication to statin therapy or indication for statin discontinuation" 1.

In summary, the decision to discontinue statins should be based on a thorough evaluation of the patient's individual risk-benefit profile, and consideration of alternative treatment options, as recommended by the most recent and highest quality guidelines 1.

From the Research

Discontinuation of Statin Therapy

Statins, or HMG-CoA reductase inhibitors, are commonly used to treat hyperlipidemia, particularly high levels of low-density lipoprotein cholesterol (LDL-C) 2. The decision to discontinue statin therapy is typically based on the occurrence of adverse events.

Adverse Events Leading to Discontinuation

The main concerns and reasons for discontinuing statin therapy include:

• Musculoskeletal side effects, such as muscle soreness or fatigue, which are the most common reason for discontinuation 2, 3
• Statin-induced myopathy, which can range from mild muscle symptoms to rare but potentially severe conditions like rhabdomyolysis 2, 4, 3
• Hepatic toxicity, characterized by increased aminotransferase levels, although this is relatively rare and often asymptomatic 4, 5

Specific Conditions for Discontinuation

Discontinuation may be considered in the following situations:

• Patients with advanced or end-stage parenchymal liver disease, due to impaired statin metabolism 5
• Patients with acute liver disease of viral or alcoholic etiology, until normalization of cytolysis enzymes 5
• Patients experiencing serious muscle injury or hepatotoxicity 4, 3

Restarting Statin Therapy

In patients who have discontinued statin therapy due to adverse events, restarting statin therapy can be considered, especially in those at high risk of cardiovascular events 3. This may involve restarting the same statin at a lower dosage or trying a different statin.

Monitoring and Safety Precautions

Regular monitoring of liver function tests and creatine kinase levels is not routinely recommended for asymptomatic patients on statin therapy 4. However, caution is needed when prescribing statins to patients with liver disease, and liver toxicity should always be monitored during statin treatment 5.