What are the effects of statin (HMG-CoA reductase inhibitor)-induced myopathy?

From the Guidelines

Statin-induced myopathy is a rare but potentially serious side effect of statin medications, and immediate discontinuation of the statin is recommended if objective muscle weakness or significant increase in creatine kinase (CK) levels is observed, as stated in the 2019 guideline by the American College of Cardiology/American Heart Association 1. The effects of statin-induced myopathy can range from mild muscle symptoms to severe rhabdomyolysis, and it is essential to assess the patient's symptoms and CK levels to determine the best course of action. Some key points to consider when evaluating statin-induced myopathy include:

• The frequency of statin-associated muscle symptoms (SAMS) is infrequent (1% to 5%) in randomized controlled trials (RCTs) but more frequent (5% to 10%) in observational studies and clinical settings 1.
• Predisposing factors for SAMS include age, female sex, low body mass index, high-risk medications, comorbidities, and excess alcohol consumption 1.
• Myositis or myopathy with concerning symptoms or objective weakness is rare, and rhabdomyolysis is exceedingly rare but requires immediate medical attention 1.
• A thorough assessment of symptoms, evaluation for non-statin etiologies, and assessment of predisposing factors are recommended before initiating statin therapy 1. If a patient develops myopathy while on statins, the approach to management should be based on the severity of symptoms and CK levels. Some possible management strategies include:
• Continuing the statin at a reduced dose or switching to a different statin with a lower myopathy risk, such as rosuvastatin or pravastatin, for mild symptoms with normal or slightly elevated CK levels 1.
• Temporarily discontinuing the statin until symptoms resolve, then rechallenging with a lower dose or different statin, for moderate symptoms or CK levels 5-10x normal.
• Immediately stopping the statin and evaluating for rhabdomyolysis for severe symptoms or CK >10x normal. Alternative approaches, such as every-other-day dosing, using the lowest effective dose, or trying non-statin lipid-lowering medications like ezetimibe or PCSK9 inhibitors, may also be considered 1.

From the FDA Drug Label

Rosuvastatin may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis with statins, including rosuvastatin The myopathy risk is greater in patients taking rosuvastatin 40 mg daily compared with lower rosuvastatin dosages. Discontinue rosuvastatin if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use, including reports of recurrence when the same or a different statin was administered

The effects of statin (HMG-CoA reductase inhibitor)-induced myopathy include:

• Myopathy: muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)
• Rhabdomyolysis: acute kidney injury secondary to myoglobinuria and rare fatalities
• Immune-mediated necrotizing myopathy (IMNM): an autoimmune myopathy characterized by proximal muscle weakness and elevated serum creatine kinase that persist despite discontinuation of statin treatment The risk of myopathy is increased with:
• Higher rosuvastatin dosage (especially 40 mg daily)
• Concomitant use with certain other drugs
• Age 65 years or greater
• Uncontrolled hypothyroidism
• Renal impairment
• Asian patients 2

From the Research

Effects of Statin-Induced Myopathy

• Statin-induced myopathy is a significant side effect of statin use, affecting 5-10% of patients in clinical practice 3
• The most common manifestation of myopathy is muscle pain, usually symmetrical and involving proximal muscles, without creatinine kinase (CK) elevation or with mild CK elevation 3
• Clinically significant rhabdomyolysis, characterized by muscle symptoms with CK elevation >10 times the upper limit of normal and creatinine elevation, is extremely rare 3, 4
• The pathophysiologic mechanism of statin-associated myopathy is unknown and probably multifactorial 3, 4

Risk Factors and Prevention

• The risk of statin-associated myopathy can be minimized by identifying vulnerable patients, such as those with impaired renal or liver function, advanced age, hypothyroidism, etc. 3
• The use of the lowest statin dose required to achieve therapeutic goals and avoiding polytherapy with drugs known to increase systemic exposure and myopathy risk can also prevent statin-related myopathy 4
• Certain patient and drug characteristics, including higher statin doses, statin cytochrome metabolism, and polypharmacy, increase the risk for statin myopathy 5
• Genetic risk factors, such as a single nucleotide polymorphism of SLCO1B1, have also been identified 5

Management and Treatment

• The management of statin-intolerant patients includes statin switching, especially to low-dose, non-daily doses of long-acting statins, such as rosuvastatin and atorvastatin 6
• Other non-statin lipid-lowering agents, such as ezetimibe and colesevelam, and possibly red yeast rice, can also be used 6
• Vitamin D supplementation may improve statin tolerance, particularly in patients with low vitamin D levels (<32 ng/mL) 7
• Coenzyme Q10 and vitamin D have been used to prevent and treat statin myopathy, but clinical trial evidence demonstrating their efficacy is limited 5