From the Guidelines
Statin-associated myopathy risk varies significantly among different statin types, with lipophilic statins generally carrying higher risk than hydrophilic ones, as reported in the 2019 guideline on the management of blood cholesterol 1.
Myopathy Incidence by Statin Type
The incidence of myopathy is highest with simvastatin and lovastatin (approximately 5-10%), followed by atorvastatin (moderate risk at 2-5%), and lowest with rosuvastatin, pravastatin, and fluvastatin (less than 2%) 1.
- Lipophilic statins, such as simvastatin and lovastatin, have a higher risk of myopathy due to their ability to penetrate muscle tissue more readily.
- Hydrophilic statins, such as rosuvastatin and pravastatin, have a lower risk of myopathy.
- Dose also matters, with high-intensity statin therapy increasing myopathy risk regardless of the specific statin.
Patient Factors Increasing Risk
Patient factors that increase the risk of myopathy include:
- Advanced age
- Female gender
- Low body mass index
- Kidney or liver disease
- Hypothyroidism
- Vitamin D deficiency
- Certain medications that interact with statins, particularly those affecting CYP3A4 metabolism
Management of Myopathy
For patients experiencing myopathy, switching to a hydrophilic statin like pravastatin or rosuvastatin at a lower dose, or using alternate-day dosing, often allows continued lipid management with reduced muscle symptoms 1.
- A comprehensive evaluation of musculoskeletal symptoms is recommended before initiating lipid-lowering therapy with a statin.
- Identifying predisposing factors for statin-associated muscle symptoms (SAMS) is crucial, including demographics, comorbid conditions, and use of medications that can adversely affect statin metabolism.
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. Pravastatin may cause myopathy and rhabdomyolysis.
The myopathy incidence varies among different statin types.
- Atorvastatin has a higher risk of myopathy at higher dosages, and the risk is increased with concomitant use of certain other drugs.
- Rosuvastatin also has a higher risk of myopathy at higher dosages (40 mg daily), and the risk is increased in Asian patients.
- Pravastatin has a lower risk of myopathy, with an incidence of less than 0.1% in clinical trials.
It is essential to consider the individual patient's risk factors, such as age, renal impairment, and concomitant medications, when prescribing statins to minimize the risk of myopathy and rhabdomyolysis 2, 3, 4.
Key points:
- Myopathy and rhabdomyolysis are potential side effects of all three statins.
- The risk of myopathy varies among statin types and dosages.
- Patient-specific risk factors should be considered when prescribing statins.
From the Research
Statin-Associated Myopathy Incidence
- The incidence of statin-associated myopathy is estimated to be around 5-10% of patients receiving statins, with muscle pain being the most common manifestation 5.
- Observational studies suggest that 10-15% of statin users develop statin-related muscle side effects, ranging from mild myalgia to more severe muscle symptoms with significant CPK elevations 6, 7.
Risk Factors for Statin-Associated Myopathy
- Patient-related risk factors include age, genetics, and co-morbidities 6, 7.
- Drug-related risk factors include statin metabolism via the CYP system, drug-drug interactions, and statin drug transport 6, 7.
- Higher statin doses and certain genetic risk factors, such as a single nucleotide polymorphism of SLCO1B1, also increase the risk of statin myopathy 7.
Statin Types and Myopathy Incidence
- Myopathy complicates the use of all statins, and the risk is dose-dependent 5.
- There is no significant difference in the tolerability rates of atorvastatin, rosuvastatin, pravastatin, and fluvastatin in patients who developed myopathy on simvastatin 8.
- Rosuvastatin has been associated with myopathy, with case reports documenting patients who developed myopathy after starting rosuvastatin 40mg once daily 9.
Management of Statin-Associated Myopathy
- Management options for statin-intolerant patients include statin switching, especially to low-dose, non-daily doses of long-acting statins, and other non-statin lipid-lowering agents, such as ezetimibe and colesevelam 5, 6, 7.
- Statin rechallenge is a real treatment option in patients with statin myopathy, and detailed history and examination are required to exclude muscle diseases unrelated to statin usage 8.