From the Guidelines
To assess muscle damage due to statin effects, the most appropriate lab order is a creatine kinase (CK) test, also known as creatine phosphokinase (CPK), 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. This blood test directly measures the level of CK enzyme that leaks into the bloodstream when muscle damage occurs.
Key Points to Consider
- Elevated CK levels, particularly those exceeding 5-10 times the upper limit of normal, strongly suggest statin-induced myopathy.
- Additional useful tests include liver function tests (ALT, AST) as statins can occasionally cause liver damage, and a comprehensive metabolic panel to assess kidney function.
- Myoglobin levels in urine or blood may also be ordered in severe cases to check for rhabdomyolysis, a dangerous condition where extensive muscle breakdown can lead to kidney damage.
- These tests should be ordered when patients on statins report muscle pain, weakness, or tenderness, which are common symptoms of statin-induced muscle damage, as stated in the guidelines 1.
Rationale for Recommendation
The mechanism behind statin myopathy involves disruption of muscle cell metabolism and mitochondrial function, leading to muscle cell damage and subsequent enzyme release into the bloodstream. According to the guidelines, in patients treated with statins, it is recommended to measure creatine kinase levels in individuals with severe statin-associated muscle symptoms, objective muscle weakness 1. However, routine measurements of creatine kinase and transaminase levels are not useful in asymptomatic patients 1. Therefore, a targeted approach to testing, based on symptoms and clinical presentation, is the most appropriate strategy for assessing muscle damage due to statin effects.
From the FDA Drug Label
Ezetimibe tablets may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis [see Adverse Reactions (6. 1)]. The lab order that will show muscle damage due to statin effect is Creatine Kinase (CK).
- CK is a key indicator of muscle damage, and elevated levels can suggest myopathy or rhabdomyolysis.
- If myopathy is suspected, discontinuation of ezetimibe tablets and other concomitant medications, such as statins, may be necessary 2.
From the Research
Lab Orders for Muscle Damage due to Statin Effect
To determine muscle damage caused by statin effect, several lab orders can be considered:
- Creatine kinase (CK) levels: Elevated CK levels are a common indicator of muscle damage, and statin-associated muscle symptoms (SAMS) have been linked to higher CK-MB values 3.
- CK-MB isoenzyme: This is a more specific marker for muscle damage, and elevated levels have been associated with SAMS 3.
- Troponin: While not as specific for muscle damage as CK or CK-MB, troponin levels can also be elevated in cases of muscle injury 3.
- Carbonic anhydrase type III: This enzyme is found in skeletal muscle and can be elevated in cases of muscle damage, although its use as a marker is less common 3.
- Alanine aminotransferase (ALT): While primarily a liver enzyme, ALT can also be elevated in cases of muscle damage, particularly if the damage is severe enough to cause liver injury 4.
Factors Influencing Lab Orders
The decision to order these lab tests may depend on various factors, including:
- Patient symptoms: Patients reporting muscle pain, weakness, or other symptoms suggestive of muscle damage may require more extensive lab testing 5, 6.
- Statin type and dose: Certain statins, such as simvastatin, may be more likely to cause muscle damage, and higher doses may increase the risk of muscle injury 3, 6.
- Patient demographics: Older patients, those with smaller body frames, or those with certain comorbidities (e.g., renal or hepatic disease) may be at higher risk of muscle damage and require more frequent lab monitoring 6, 7.
- Concomitant medications: Patients taking other medications that may increase the risk of muscle injury (e.g., certain antibiotics or antifungals) may require more frequent lab testing 4.