What is the significance of a creatine kinase (CK) increase from 217 to 248 units after discontinuing statin (HMG-CoA reductase inhibitor) therapy 3 weeks prior?

From the Guidelines

The increase in CK from 217 to 248 three weeks after stopping a statin is not clinically significant and does not require any specific intervention, as it falls within the normal biological variation of CK levels 1. This small elevation (approximately 14%) can be due to various factors unrelated to the medication, such as exercise or muscle injury. According to the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol, statin-associated muscle symptoms (SAMS) are common, but significant increases in CK levels are rare 1. The guideline recommends a comprehensive evaluation of musculoskeletal symptoms before initiating statin therapy and identifying predisposing factors for SAMS, including demographics, comorbid conditions, and use of medications that can adversely affect statin metabolism 1. If you experience muscle pain, weakness, or tenderness, or if your CK levels continue to rise significantly (typically above 5-10 times the upper limit of normal), it is essential to contact your healthcare provider. The minor CK elevation observed is not indicative of rhabdomyolysis or significant muscle damage, and statin-associated muscle symptoms typically improve within weeks of discontinuation, with CK levels normalizing or decreasing rather than increasing after stopping the medication 1. This pattern suggests other factors may be influencing your CK levels, and it is crucial to consider these factors when evaluating the increase in CK levels. You can safely continue without the statin if it was stopped due to concerns about muscle symptoms, or consider restarting the statin if it was providing important cardiovascular benefits, while closely monitoring your CK levels and muscle symptoms.

From the FDA Drug Label

Discontinue atorvastatin calcium tablets if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK elevations may resolve if atorvastatin calcium tablets are discontinued The increase in CK from 217 to 248 after stopping statin may be related to immune-mediated necrotizing myopathy (IMNM), which is characterized by proximal muscle weakness and elevated serum creatine kinase that persists despite discontinuation of statin treatment.

• Key points:
  • CK elevation may be a sign of myopathy
  • IMNM is a possible cause of persistent CK elevation after statin discontinuation
  • Further testing, such as muscle biopsy and serologic testing, may be necessary to diagnose IMNM 2 It is recommended to discontinue the statin and consider further evaluation and treatment with immunosuppressive agents if IMNM is suspected.

From the Research

CK Increase After Stopping Statin

• The increase in CK from 217 to 248 three weeks after stopping statin is observed in the given scenario.
• According to the study 3, increases in creatine kinase (CK) levels during high-dose atorvastatin treatment are not associated with changes in skeletal muscle function and symptoms.
• However, the study 3 does not specifically address the scenario of CK increase after stopping statin, but it does provide insight into the effects of statins on CK levels.
• Another study 4 suggests that high pretreatment CK levels should not be an impediment to starting or continuing statins, but it does not directly address the issue of CK increase after stopping statin.
• The study 5 found that higher intensity statin therapy increases the incidence of transaminase elevations and may increase the risk of CK elevations, but it does not provide information on CK levels after stopping statin.
• The study 6 examined the risk for significant CK elevation with statins and found that simvastatin use was associated with a higher likelihood for CK elevation than lovastatin, but it does not address the scenario of CK increase after stopping statin.
• The study 7 found that statins cause dose-dependent borderline elevations of liver function tests over time, but it does not provide information on CK levels after stopping statin.

Possible Factors Influencing CK Increase

• The exact cause of the CK increase after stopping statin is not clear from the provided studies.
• However, the studies suggest that statins can affect CK levels, and the increase in CK after stopping statin may be related to the withdrawal of the statin's effects on muscle function and CK levels.
• Further research is needed to fully understand the relationship between statin use and CK levels, particularly after stopping statin.