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Statin-associated Myopathy

General Information

General InformationGeneral Information


  • muscle pain and weakness developing in response to statin treatment2,3,4,5

Also called

  • statin-associated muscle adverse events
  • statin-related myopathy
  • statin-induced myopathy


  • myopathy has been used to refer either specifically to muscle weakness or to general condition of muscular disease
  • definitions used in American College of Cardiology/American Heart Association/National Heart, Lung and Blood Institute (ACC/AHA/NHLBI) 2002 clinical advisory1
    • myopathy - any disease of muscles (can be acquired or inherited and can occur at birth or later in life)
    • myalgia - muscle ache or weakness without creatine kinase (CK) elevation
    • myositis - muscle symptoms with increased CK levels
    • rhabdomyolysis - muscle symptoms with significant CK elevation (usually > 10 times upper limit of normal) and elevated serum creatinine (usually with brown urine and urinary myoglobin)
  • definitions used by the National Lipid Association Statin Muscle Safety Task Force2
    • myalgia - muscle pain (see modified statin-myalgia clinical index score)
    • myonecrosis - muscle injury, graded by degree of hyperCKemia (based if possible on patient's normal CK value)
      • mild > 3 times baseline CK, or upper limit of normal (adjusted for race, age, and sex)
      • moderate ≥ 10 times baseline CK, or upper limit of normal (adjusted for race, age, and sex)
      • severe ≥ 50 times baseline CK, or upper limit of normal (adjusted for race, age, and sex)
    • clinical rhabdomyolysis: myonecrosis with myoglobinuria or acute renal failure (serum creatinine increase of ≥ 0.5 mg/dL)
    • myopathy - muscle weakness
    • myositis - muscle inflammation, typically associated with muscle tenderness and pain (determined either through magnetic resonance imaging or muscle biopsy)
  • statin-associated autoimmune myopathy is rare condition in which CK levels do not decrease after statin is removed4


  • statin-associated myopathy - generally considered toxic reaction to statins that resolves upon statin cessation
  • statin-associated autoimmune myopathy - a statin-associated form of immune-mediated necrotizing myopathy with similar symptoms but muscle damage usually persists even after statin withdrawal



General references used

  1. Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al. ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. Circulation. 2002 Aug 20;106(8):1024-8full-text
  2. Rosenson RS, Baker SK, Jacobson TA, Kopecky SL, Parker BA, The National Lipid Association's Muscle Safety Expert Panel. An assessment by the Statin Muscle Safety Task Force: 2014 update. J Clin Lipidol. 2014 May-Jun;8(3 Suppl):S58-71
  3. Stroes ES, Thompson PD, Corsini A, et al. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015 May 1;36(17):1012-22full-text
  4. Mammen AL. Statin-Associated Autoimmune Myopathy. N Engl J Med. 2016 Feb 18;374(7):664-9
  5. Mancini GB, Baker S, Bergeron J, et al. Diagnosis, Prevention, and Management of Statin Adverse Effects and Intolerance: Canadian Consensus Working Group Update (2016). Can J Cardiol. 2016 Jul;32(7 Suppl):S35-65

Recommendation grading systems used

  • American College of Cardiology/American Heart Association (ACC/AHA) grading system for recommendations
    • classifications of recommendations
      • Class I - procedure or treatment should be performed or administered
      • Class IIa - reasonable to perform procedure or administer treatment, but additional studies with focused objectives needed
      • Class IIb - procedure or treatment may be considered; additional studies with broad objectives needed, additional registry data would be useful
      • Class III - procedure or treatment should not be performed or administered because it is not helpful or may be harmful
        • Class III ratings may be subclassified as Class III No Benefit or Class III Harm
    • levels of evidence
      • Level A - data derived from multiple randomized clinical trials or meta-analyses
      • Level B - data derived from single randomized trial or nonrandomized studies
      • Level C - only expert opinion, case studies, or standard of care
  • National Lipid Association (NLA) Statin Muscle Safety expert panel recommendation grading system
    • strength of recommendation
      • Strong - high certainty based on the evidence that the net benefit is substantial
      • Moderate - moderate certainty based on the evidence that the net benefit is moderate to substantial, or there is high certainty that the net benefit is moderate
      • Weak - at least moderate certainty based on the evidence that there is a small net benefit
      • Recommend Against - at least moderate certainty based on the evidence that it has no net benefit or that the risks/harms outweigh benefits
      • Expert Opinion - insufficient evidence or evidence is unclear or conflicting, but this is what the expert panel
      • No Recommendation for or against - insufficient evidence or evidence is unclear or conflicting
    • quality of evidence
      • High
        • well-designed, well-executed randomized controlled trials (RCTs) that adequately represent populations to which the results are applied and directly assess effects on health outcomes
        • well-conducted meta-analyses of such studies
        • highly certain about the estimate of effect; more research is unlikely to change our confidence in the estimate of effect
      • Moderate
        • RCTs with minor limitations affecting confidence in, or applicability of, the results
        • well-designed, well-executed nonrandomized controlled studies and well-designed
        • well-executed observational studies
        • well-conducted -meta-analysis of such studies
        • moderately certain about the estimate of effect; additional research may have an impact on our confidence in the estimate of effect and may change the estimate
      • Low
        • RCTs with major limitations
        • nonrandomized controlled studies and observational studies with major limitations affecting confidence in, or applicability of, the results
        • uncontrolled clinical observations without an appropriate comparison group (such as case series, case reports)
        • physiological studies in humans
        • meta-analyses of such studies
        • low certainty about the estimate of effect; further research is likely to have an impact on our confidence in the estimate of effect and is likely to change the estimate
    • Reference - NLA Muscle Safety Expert Panel 2014 update (24793443J Clin Lipidol 2014 May-Jun;8(3 Suppl):S58)

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How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T361018, Statin-associated Myopathy; [updated 2018 Nov 30, cited place cited date here]. Available from Registration and login required.

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