What is the significance of elevated Creatine Kinase (CK) levels, from 217 to 248, three weeks after discontinuing atorvastatin (lipitor), in a 70-year-old male with no new muscle symptoms?

From the Guidelines

I recommend restarting atorvastatin as the mild CK elevation is likely not clinically significant statin-related myopathy. The patient's CK levels (217 initially, increasing to 248 after stopping atorvastatin) are only mildly elevated above normal range (typically <200 U/L for men), and importantly, the patient denies muscle symptoms. Asymptomatic CK elevations less than 4-5 times the upper limit of normal generally don't require statin discontinuation, as stated in the 2019 guideline on the management of blood cholesterol by the American College of Cardiology/American Heart Association task force on clinical practice guidelines 1.

The continued rise in CK after stopping atorvastatin suggests other factors may be contributing to the elevation, such as recent exercise, muscle trauma, or underlying medical conditions. When restarting atorvastatin, consider using the same dose if previously well-tolerated, or a lower dose with gradual titration if there are concerns. Monitor CK levels and symptoms in 4-6 weeks. The cardiovascular benefits of statins typically outweigh the risks in a 70-year-old male who likely has indications for statin therapy. If CK levels continue to rise significantly or the patient develops muscle symptoms, reassessment would be warranted.

Some key points to consider in this case include:

• The frequency of statin-associated muscle symptoms (SAMS), which can range from infrequent (1% to 5%) in randomized controlled trials (RCTs) to frequent (5% to 10%) in observational studies and clinical settings 1.
• The importance of evaluating musculoskeletal symptoms before initiating statin therapy and identifying predisposing factors for SAMS, such as demographics, comorbid conditions, and use of medications that can adversely affect statin metabolism 1.
• The rare but serious risk of myositis/myopathy (CK > ULN) with concerning symptoms or objective weakness, which requires prompt statin cessation and evaluation for reversible causes 1.

From the Research

Patient Profile

• Male, 70 years old
• Initial CK level: 217
• Atorvastatin was stopped
• CK level increased to 248 three weeks later
• Denies new muscle aches

Relevant Studies

• A study published in 2009 2 found that asymptomatic patients with high CK levels (>or=250 but <2500 IU/L) can tolerate statins well without developing myalgia-myositis.
• The study suggests that high pretreatment CK levels, particularly 1 to 5 times the upper normal limit, should not be an impediment to starting or continuing statins to lower LDL-C.
• Another study published in 2021 3 reported a rare case of asymptomatic hyperCKemia with levels >80 times the upper limit of normal, which was refractory to fluid resuscitation.
• However, this case was found to be caused by elevated macroenzymes-macroCKemia, a rare and benign cause of CK elevation.

Statin-Associated CK Elevation

• A study published in 2010 4 examined the risk for significant CK elevation with statins and found that simvastatin use was associated with a higher likelihood for CK > or =10x ULN than lovastatin.
• The study also found that high-dose simvastatin and interacting medications can increase the risk of CK elevation.
• However, the patient in question was taking atorvastatin, which was stopped, and the CK level increased three weeks later.

Alternative Treatment Options

• Studies published in 2021 5, 6 discussed the use of rosuvastatin and ezetimibe for the treatment of dyslipidemia and hypercholesterolemia.
• The combination of rosuvastatin and ezetimibe was found to be safe and effective in reducing LDL-C levels, with a good safety profile in a broad spectrum of patients.
• However, these studies did not specifically address the issue of CK elevation in patients taking statins.