Should Creatine Kinase (CK) levels be monitored during statin (HMG-CoA reductase inhibitor) therapy?

From the Guidelines

Monitoring Creatine Kinase (CK) Levels During Statin Therapy

No, routine monitoring of Creatine Kinase (CK) levels is not recommended for patients on statin therapy, as stated in the guidelines 1.

Exceptions for CK Monitoring

However, there are specific situations where measuring CK levels is reasonable:

• In individuals with severe statin-associated muscle symptoms, objective muscle weakness, or those believed to be at increased risk for adverse muscle events due to personal or family history of statin intolerance or muscle disease 1.
• In patients with muscle symptoms such as pain, tenderness, stiffness, cramping, weakness, or generalized fatigue while on statin therapy 1.

Rationale Behind the Recommendation

The recommendation against routine CK monitoring is based on the lack of evidence that it improves clinical outcomes and the low incidence of severe statin-associated muscle symptoms 1. The guidelines emphasize that the benefits of statin therapy outweigh the risks, including the risk of new-onset diabetes mellitus, and that statin therapy should not be discontinued due to this risk 1.

Clinical Considerations

Clinicians should be aware of the potential for statin-associated side effects, including muscle symptoms and hepatotoxicity, and should monitor patients for these adverse effects, particularly those at increased risk 1. However, routine measurements of CK and transaminase levels are not useful in asymptomatic patients on statin therapy 1.

From the FDA Drug Label

Atorvastatin calcium may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Discontinue atorvastatin calcium tablets if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected.

Monitoring of Creatine Kinase (CK) levels is recommended during statin (HMG-CoA reductase inhibitor) therapy, particularly if patients are at high risk of developing myopathy or rhabdomyolysis, or if they experience muscle symptoms such as pain, tenderness, or weakness.

• Key factors that increase the risk of myopathy and rhabdomyolysis include:
  • Age 65 years or greater
  • Uncontrolled hypothyroidism
  • Renal impairment
  • Concomitant use with certain other drugs
  • Higher statin dosage
• Action to take if markedly elevated CK levels occur or if myopathy is suspected:
  • Discontinue statin therapy
  • Temporarily discontinue statin therapy in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis 2, 3, 3

From the Research

Monitoring Creatine Kinase (CK) Levels During Statin Therapy

• CK levels should be monitored during statin therapy, as muscle toxicity is a significant adverse effect related to statins 4.
• Asymptomatic CK level elevation is common, with 43% of patients in one study experiencing this condition 4.
• The severity of muscle injury and CK levels can guide the clinical approach, with statin therapy potentially being continued safely and effectively in cases of asymptomatic CK levels <3-5 upper limit of normal (ULN) 4.
• However, when CK levels >3-5 ULN or symptomatic muscle adverse reactions are present, statin rechallenge should be individualized, and an additional lipid medication may be advised if target levels are not achieved 4.

Relationship Between CK Levels and Statin-Associated Muscle Symptoms (SAMS)

• SAMS can occur with normal CK levels, as demonstrated by a study where four patients developed muscle symptoms and myopathy despite normal CK levels 5.
• Another study found that simvastatin use, BMI, and CK-MB were independent markers of SAMS, with patients experiencing SAMS having greater BMI and higher CK-MB values 6.
• The relationship between SAMS and biomarkers of muscle damage, including CK, CK-MB, troponin, and carbonic anhydrase type III, has been examined, with results suggesting that CK-MB and BMI are associated with SAMS 6.

Therapeutic Consequences of CK Increase Under Statin Therapy

• If myopathy symptoms are present or CK levels are greater than 5 times the upper limits of normal, statin therapy should be discontinued 7.
• In cases of asymptomatic CK increase below 5 times the upper limits of normal, therapy can be continued with CK monitoring 7.
• Creatine supplementation does not alter the CK response to eccentric exercise in healthy adults on atorvastatin, suggesting that other strategies may be needed to mitigate statin-associated muscle symptoms in physically active individuals 8.