Can new-onset myopathy (muscle disease) develop in patients taking statins (HMG-CoA reductase inhibitors) years after initiation of therapy?

From the Guidelines

Yes, it is possible to develop new onset myopathy from statin medications even after years of use without previous problems. Statins like atorvastatin (Lipitor), rosuvastatin (Crestor), and simvastatin (Zocor) can cause muscle symptoms at any point during treatment, not just when first starting the medication. These symptoms may range from mild muscle pain (myalgia) to more severe conditions like myositis (muscle inflammation) or, rarely, rhabdomyolysis (severe muscle breakdown). Risk factors that might trigger late-onset statin myopathy include:

• starting new medications that interact with statins (particularly certain antibiotics, antifungals, and some heart medications)
• developing kidney or liver problems
• thyroid disorders
• vitamin D deficiency
• increased physical activity If you develop unexplained muscle pain, weakness, or tenderness while on a statin, even after years of use, contact your healthcare provider immediately. They may recommend temporarily stopping the statin, checking creatine kinase levels (a marker of muscle damage), or switching to a different statin or dosing regimen. This delayed reaction occurs because statins can gradually affect muscle cell metabolism by depleting coenzyme Q10 and altering muscle cell energy production over time, as suggested by guidelines from the American College of Cardiology and American Heart Association 1.

From the FDA Drug Label

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 IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persists despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents.

Yes, it is possible to develop new onset myopathy on statins years after using it, as there have been rare reports of immune-mediated necrotizing myopathy (IMNM) associated with statin use, including recurrence when the same or a different statin was administered 2.

• Key factors that may increase the risk of myopathy include age, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs, and higher statin dosage.
• IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persists despite discontinuation of statin treatment.
• Treatment with immunosuppressive agents may be required, and simvastatin should be discontinued if IMNM is suspected 3.

From the Research

Statin-Associated Myopathy

• Statin-associated muscle symptoms are a relatively common condition that may affect 10% to 15% of statin users 4, 5.
• The etiology of myopathy is multifactorial, and certain patient and drug characteristics increase the risk for statin myopathy, including higher statin doses, statin cytochrome metabolism, and polypharmacy 4.
• Statin myopathy includes a wide spectrum of clinical conditions, ranging from mild myalgia to rhabdomyolysis 4, and can be dose-dependent 5.

Development of Myopathy Years After Statin Use

• There is no direct evidence to suggest that new onset myopathy cannot develop years after using statins.
• However, studies suggest that statin-associated myopathy can occur at any time during statin therapy, and the risk of myopathy can be minimized by identifying vulnerable patients and avoiding statin interactions with specific drugs 5.
• It is essential to note that not all patients taking statins who develop muscle complaints have statin-related myopathy, and a thorough clinical evaluation and appropriate testing are warranted to avoid an unnecessary increase in cardiovascular risk 6.

Management of Statin-Intolerant Patients

• 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 7.
• In some cases, statin-intolerant patients may be successfully treated with either low-dose statins, alternate-day dosing, or using twice-weekly dosing with longer half-life statins 4.
• The use of coenzyme Q10 and vitamin D has been suggested to prevent and treat statin myopathy, but clinical trial evidence demonstrating their efficacy is limited 4.