diagnostic approach to possible statin induced myopathy

Last reviewed 06/2023

Approach to statin-induced myopathy

• first consideration is to whether the symptoms due to the statin?
  • many patients who develop significant weakness and pain on statin therapy have normal CK levels (1)
  • first objective is to determine the likelihood that the muscle complaint is being caused by statin therapy
    • factors that make statin toxicity more likely must be weighed against any features that are atypical or that favour an alternate diagnosis
    • final decision about future statin treatment depends on the balance between the expected benefit of statin therapy for each individual and the likelihood that the symptoms are due to statin therapy
      
      
• findings from the history that implicate statins
  • often muscle symptoms resolve within 2 weeks of starting statin therapy
    • if patients have a normal CK level and can tolerate the symptoms, ask them to continue therapy and see if their symptoms resolve with continued use. Symptoms that persist beyond the first 2 weeks of therapy are likely due to the statin
      • include symmetric burning or pain in the large muscles during exercise that was not present before lipid-lowering therapy
      • any symptom that reproducibly recurs with statin rechallenge and disappears within 2 weeks of discontinuing therapy is more likely to be caused by the statin
        
        
• is the patient a vegetarian? A drinker? Taking supplements?
  • taking a careful history of diet and supplement use is important to find exposures that may increase the risk of statin-related muscle complaints
    • vegetarians may develop carnitine or vitamin B12 deficiencies
    • alcohol and vitamin E and other supplements are occasional causes of muscle symptoms falsely attributed to statin therapy
    • red yeast rice contains lovastatin, which can exacerbate myopathy, especially when taken in conjunction with another statin
      
      
• physical examination
  • the examination of patients with possible statin-induced myopathy begins with a general assessment for signs of hypothyroidism or excess alcohol consumption
  • ankle-brachial indices are used to exclude significant peripheral vascular disease
  • musculoskeletal examination focuses on muscle atrophy, tone, tenderness and strength but also excludes tendinopathies, arthropathies, and myofascial pain syndromes, which are often confused with muscle pain
    
    
• investigations
  • CK level (preferably more than 72 hours after exercise)
  • vitamin D level
  • TSH
  • further laboratory evaluation depends on the findings and will often be directed by specialist advice
    • other investigations include
      • FBC, ESR, CRP, anti-Ro and anti-La antibodies, and the myositis panel in patients with elevated CK whose other findings suggest an autoimmune or inflammatory process
      • serum carnitine levels (free, total, and esterified), fasting serum lactate levels, and serum cortisol in those with findings suggestive of metabolic myopathy
      • electromyography and nerve conduction studies in patients with possible myelopathy, peripheral neuropathy, or inflammatory myopathy
      • muscle biopsy may be necessary to exclude inflammatory or necrotizing myopathies in patients whose CK remains elevated despite withdrawal of statins
        • may also be helpful when other findings suggest a metabolic myopathy
        • if a biopsy is needed, magnetic resonance imaging of the affected limb may identify an affected muscle for biopsy
          
          

Reference:

• 1) Fernandez G et al. Statin myopathy: a common dilemma not reflected in clinical trials. Cleve Clin J Med. 2011 Jun;78(6):393-403