What is the effect of HMG-CoA reductase inhibitors (statins) on creatine kinase (CK) levels?

From the Guidelines

Statin therapy is associated with an increased risk of elevated creatine kinase (CK) levels, particularly in patients with predisposing factors such as muscle disease, renal or hepatic dysfunction, or concomitant use of certain medications, and CK levels should be measured in individuals with severe statin-associated muscle symptoms or objective muscle weakness 1.

Key Points

• Baseline CK levels should be checked before initiating statins in high-risk patients, such as those with kidney disease, hypothyroidism, personal or family history of muscle disorders, or taking medications that interact with statins 1.
• Routine measurements of CK and transaminase levels are not useful in patients treated with statins, unless they develop muscle symptoms or signs of hepatotoxicity 1.
• If a patient on statins develops muscle symptoms, CK levels should be measured immediately, and the statin should be discontinued if the CK levels are severely elevated (>10x upper limit of normal) or if rhabdomyolysis is suspected 1.
• For patients with mild to moderate CK elevations (5-10x ULN), consider dose reduction or temporary discontinuation with close monitoring, and restart with a lower dose or different statin if symptoms resolve and CK normalizes after stopping the statin 1.

Management of Statin-Associated Muscle Symptoms

• Evaluate patients for other conditions that might increase the risk for muscle symptoms, such as hypothyroidism, reduced renal or hepatic function, or rheumatologic disorders 1.
• Consider other causes of muscle symptoms if they persist after 2 months without statin treatment, and resume statin therapy at the original dose if the symptoms are determined to be unrelated to statin therapy or if the predisposing condition has been treated 1.

Prevention of Statin-Associated Muscle Symptoms

• Hydration, avoiding excessive exercise, and addressing drug interactions can help minimize statin-associated muscle symptoms and CK elevations 1.
• Use caution when initiating statin therapy in individuals >75 years of age or in those taking concomitant medications that alter drug metabolism, and review the manufacturer's prescribing information before initiation of any cholesterol-lowering drug 1.

From the FDA Drug Label

Atorvastatin calcium may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Rosuvastatin may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis.

HMG-CoA reductase inhibitors (statins), such as rosuvastatin and atorvastatin, may cause myopathy and rhabdomyolysis, which are associated with elevated creatine kinase (CK) levels.

• Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher statin dosage.
• Discontinuation of the statin is recommended if markedly elevated CK levels occur or if myopathy is diagnosed or suspected.
• Temporarily discontinuing the statin is recommended in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis 2, 3, 3.

From the Research

Effect of HMG-CoA Reductase Inhibitors (Statins) on Creatine Kinase (CK) Levels

• Statins can cause muscle toxicity, which is the most significant adverse effect related to their use 4.
• Asymptomatic serum creatine kinase (CK) level elevation is a common side effect of statin therapy, occurring in 43% of patients in one study 4.
• Elevated CK levels can be a marker of statin-associated myotoxicity, which can range from asymptomatic CK elevation to muscle pain, weakness, and rhabdomyolysis 5, 6.
• The use of simvastatin, CK-MB, and BMI are independent variables for statin-associated muscle symptoms (SAMS) and elevated CK levels 7.
• Patients reporting musculoskeletal symptoms have significantly higher mean CK levels than those not reporting any musculoskeletal symptoms 8.
• CK monitoring is relatively selective in relation to risks and patient-reported adverse symptoms, with patients taking atorvastatin or rosuvastatin, and patients with a history of chronic renal diseases being more likely to have CK monitored on initiation of and during statin treatment 8.

Management of Statin-Induced Muscle Toxicity

• For patients with asymptomatic CK levels <3-5 upper limit of normal (ULN), statin treatment should not be interrupted 4.
• When CK levels >3-5 ULN or when various symptomatic muscle adverse reactions are present, statins rechallenge, after a recovery period, should be individualized either by a low dose of a potent statin or by a less potent statin 4.
• An additional lipid medication is advised if the target levels are not achieved 4.
• A practical approach to diagnosing and managing patients with statin side effects, including muscle toxicity, is necessary to minimize adverse effects while still lowering low-density lipoprotein (LDL) levels 5.