Statin-Induced Myopathy

Aka: Statin-Induced Myopathy, Rhabdomyolysis due to Statin, Statin-Induced Myalgias, Myositis due to Statins, Statin Myopathy, Statin Intolerance

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II. Epidemiology

  1. Statin-Induced Myalgias are common (5-30%)
    1. However, Placebo results in similar myalgia rates (27%), especially in the first year
    2. High intensity Statin doses are slightly more likely to cause myalgias
    3. Most myalgias (>90%) are due to other causes (see differential diagnosis below), or due to Nocebo Effect
    4. (2022) Lancet 400(10355):832-45 +PMID: 36049498 [PubMed]
  2. Statin-induced Rhabdomyolysis is very uncommon (<0.01%)
    1. Davidson (2006) Am J Cardiol 97(8A):32C–43C [PubMed]
    2. Mendes (2014) Physiother Can 66(2): 124–132 [PubMed]

III. Mechanism

  1. Typical Myopathy
    1. Muscle injury secondary to Statin use (drug-induced Myopathy - accelerating Muscle Cell death)
  2. Statin-Induced Immune-mediated Necrotizing Myopathy
    1. Newly defined in 2011
    2. Symptoms and findings (including CPK) remain abnormal after stopping the Statin

IV. Symptoms

  1. Myalgia
    1. Muscle ache or weakness with normal CPK
  2. Myostitis
    1. Muscle ache or weakness with CPK elevated but <10 fold increase above normal
  3. Rhabdomyolysis
    1. Muscle ache or weakness with CPK elevated but >10 fold increase above normal

V. Symptoms: Red Flags

  1. Patient should stop Statin and contact physician if following symptoms experienced
  2. Severe myalgias
  3. Muscle Weakness
  4. Dark Urine

VI. Labs

  1. Creatine Phosphokinase (CPK)
    1. Poor marker for myalgias (only increased in Myositis or Rhabdomyolysis)
    2. Normal in most patients despite myalgias
    3. Abnormal CPK suggests Myositis or Rhabdomyolysis and requires immediate cessation of Statin
  2. Additional labs in CPK Elevation (especially Rhabdomyolysis)
    1. Urine Myoglobin
    2. Renal Function
  3. Labs to consider in differential diagnosis
    1. Vitamin D Level
    2. Thyroid Stimulating Hormone (TSH)

VII. Differential Diagnosis

  1. See Myopathy Causes
  2. Vitamin D Deficiency
  3. Hypothyroidism

VIII. Risk factors: Statin induced Myopathy

  1. Statin combination with Gemfibrozil (and to a lesser extent with Fenofibrate)
  2. Drug Interactions (see Statins)
    1. Raised serum Statin levels result in higher myalgia or Myositis risk
  3. Older patients over age 70 years
  4. Low body weight
  5. Female gender
  6. Acute illness or major surgery
  7. Alcohol Abuse or other Substance Abuse (e.g. Cocaine, Amphetamines)
  8. Hypothyroidism
  9. Chronic Kidney Disease Stage 4 (Creatinine Clearance <30 ml/min)
  10. High dose Statin use (dose greater than 50% of maximum dose, especially Simvastatin 80 mg)

IX. Management: Symptomatic Statin-Induced Myalgias and Statin Intolerance

  1. Background
    1. More than 70% of Statin-intolerant patients find a tolerable Statin regimen
    2. More than 90% of myalgias in patients taking Statins are NOT due to other cause or Nocebo Effect (see above)
    3. Strategies here may also apply to other Statin Intolerance causes (beyond myalgias)
  2. Coenzyme Q10 (Ubiquinone) 100 mg orally daily
    1. Reduces myalgias by 40% in one study (other studies show no efficacy)
    2. Caso (2007) Am J Cardiol 99:1409-12 [PubMed]
  3. Decrease Statin dose by 50%
  4. Consider alternate day dosing or twice weekly dosing of a higher potency Statin (e.g. Rosuvastatin, Atorvastatin)
    1. May lower LDL 30% of baseline when consistently followed, but other options are preferred
  5. Consider Ezetimibe as an adjunct to allow lowering Statin dose
  6. Consider other causes (e.g. Hypothyroidism, Vitamin D Deficiency, Fibromyalgia)
    1. See Myopathy Causes
  7. Consider a trial off Statin for 4-6 weeks
    1. If myalgias persist, Statin was unlikely to be the cause
  8. Consider Drug Interactions and other predisposing medications
    1. See CYP3A3/4 Inhibitor
    2. Fibrates (e.g. Gemfibrozil, Fenofibrate)
    3. Colchicine
    4. Verapamil
    5. Corticosteroids
  9. Consider change to alternative Statin
    1. Initially thought that hydrophilic Statins (Pravastatin, Rosuvastatin) were less likely to cause myalgias
    2. Hydrophilic Statins do not appear to offer any increased benefit over other Statins regarding myalgia risk
      1. Thompson (2003) JAMA 289(13): 1681-90 [PubMed]
  10. References
    1. (2022) Presc Lett, August Issue, accessed online 8/2/2022
    2. Cheeley (2022) J Clin Lipidol +PMID: 35718660 [PubMed]

X. References

  1. Bruckert (2005) Cardiovasc Drugs Ther 19(6): 403-14 [PubMed]
  2. Graham (2004) JAMA 292(21): 2585-90 [PubMed]
  3. Phillips (2002) Ann Intern Med 137:581-5 [PubMed]

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