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Statin-associated Myopathy

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General Information

General InformationGeneral Information

Description

  • 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

Definitions

  • 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

Types

  • 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

References

References

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):1024-8OpenInNewfull-textOpenInNew
  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):S58-71OpenInNew
  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):1012-22OpenInNewfull-textOpenInNew
  4. Mammen AL. Statin-Associated Autoimmune Myopathy. N Engl J Med. 2016 Feb 18;374(7):664-9OpenInNew
  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):S35-65OpenInNew

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):S58OpenInNew)

Synthesized Recommendation Grading System for DynaMed

  • DynaMed systematically monitors clinical evidence to continuously provide a synthesis of the most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based MethodologyOpenInNew).
  • Guideline recommendations summarized in the body of a DynaMed topic are provided with the recommendation grading system used in the original guideline(s), and allow DynaMed users to quickly see where guidelines agree and where guidelines differ from each other and from the current evidence.
  • In DynaMed (DM), we synthesize the current evidence, current guidelines from leading authorities, and clinical expertise to provide recommendations to support clinical decision-making in the Overview & Recommendations section.
  • We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE)OpenInNew to classify synthesized recommendations as Strong or Weak.
    • Strong recommendations are used when, based on the available evidence, clinicians (without conflicts of interest) consistently have a high degree of confidence that the desirable consequences (health benefits, decreased costs and burdens) outweigh the undesirable consequences (harms, costs, burdens).
    • Weak recommendations are used when, based on the available evidence, clinicians believe that desirable and undesirable consequences are finely balanced, or appreciable uncertainty exists about the magnitude of expected consequences (benefits and harms). Weak recommendations are used when clinicians disagree in judgments of relative benefit and harm, or have limited confidence in their judgments. Weak recommendations are also used when the range of patient values and preferences suggests that informed patients are likely to make different choices.
  • DynaMed (DM) synthesized recommendations (in the Overview & Recommendations section) are determined with a systematic methodology:
    • Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological expertise and ≥ 1 with content domain expertise) aware of the best current evidence for benefits and harms, and the recommendations from guidelines.
    • Recommendations are phrased to match the strength of recommendation. Strong recommendations use "should do" phrasing, or phrasing implying an expectation to perform the recommended action for most patients. Weak recommendations use "consider" or "suggested" phrasing.
    • Recommendations are explicitly labeled as Strong recommendations or Weak recommendations when a qualified group has explicitly deliberated on making such a recommendation. Group deliberation may occur during guideline development. When group deliberation occurs through DynaMed-initiated groups:
      • Clinical questions will be formulated using the PICO (Population, Intervention, Comparison, Outcome) framework for all outcomes of interest specific to the recommendation to be developed.
      • Systematic searches will be conducted for any clinical questions where systematic searches were not already completed through DynaMed content development.
      • Evidence will be summarized for recommendation panel review including for each outcome, the relative importance of the outcome, the estimated effects comparing intervention and comparison, the sample size, and the overall quality rating for the body of evidence.
      • Recommendation panel members will be selected to include at least 3 members that together have sufficient clinical expertise for the subject(s) pertinent to the recommendation, methodological expertise for the evidence being considered, and experience with guideline development.
      • All recommendation panel members must disclose any potential conflicts of interest (professional, intellectual, and financial), and will not be included for the specific panel if a significant conflict exists for the recommendation in question.
      • Panel members will make Strong recommendations if and only if there is consistent agreement in a high confidence in the likelihood that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. Panel members will make Weak recommendations if there is limited confidence (or inconsistent assessment or dissenting opinions) that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. No recommendation will be made if there is insufficient confidence to make a recommendation.
      • All steps in this process (including evidence summaries which were shared with the panel, and identification of panel members) will be transparent and accessible in support of the recommendation.
    • Recommendations are verified by ≥ 1 editor with methodological expertise, not involved in recommendation drafting or development, with explicit confirmation that Strong recommendations are adequately supported.
    • Recommendations are published only after consensus is established with agreement in phrasing and strength of recommendation by all editors.
    • If consensus cannot be reached then the recommendation can be published with a notation of "dissenting commentary" and the dissenting commentary is included in the topic details.
    • If recommendations are questioned during peer review or post publication by a qualified individual, or reevaluation is warranted based on new information detected through systematic literature surveillance, the recommendation is subject to additional internal review.

DynaMed Editorial Process

Special acknowledgements

  • DynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.
  • Editorial Team role definitions
    Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic Editors also serve as consultants for the internal DynaMed Editorial Team during the writing and editing process, and review the final topic drafts prior to publication.
    Section Editors have similar responsibilities to Topic Editors but have a broader role that includes the review of multiple topics, oversight of Topic Editors, and systematic surveillance of the medical literature.
    Recommendations Editors provide explicit review of DynaMed Overview and Recommendations sections to ensure that all recommendations are sound, supported, and evidence-based. This process is described in "Synthesized Recommendation Grading."
    Deputy Editors are employees of DynaMed and oversee DynaMed internal publishing groups. Each is responsible for all content published within that group, including supervising topic development at all stages of the writing and editing process, final review of all topics prior to publication, and direction of an internal team.

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 https://www.dynamed.com/topics/dmp~AN~T361018. Registration and login required.
  • KeyboardArrowRight

    Overview and Recommendations

    • Background

    • Evaluation

    • Management

  • Related Summaries

  • Overview

  • KeyboardArrowRight

    General Information

    • Description

    • Also called

    • Definitions

    • Types

  • KeyboardArrowRight

    Epidemiology

    • KeyboardArrowRight

      Incidence/Prevalence

      • Statin monotherapy

    • Likely risk factors

  • KeyboardArrowRight

    Etiology and Pathogenesis

    • Causes

    • Pathogenesis

  • KeyboardArrowRight

    History and Physical

    • KeyboardArrowRight

      History

      • Chief concern

      • History of present illness (HPI)

      • Medication history

    • KeyboardArrowRight

      Physical

      • General physical

      • Neuro

  • KeyboardArrowRight

    Diagnosis

    • Making the diagnosis

    • Differential diagnosis

    • Testing overview

    • KeyboardArrowRight

      Blood tests

      • Creatine kinase

      • HMGCoA reductase antibody testing

    • Imaging studies

    • Biopsy and pathology

    • Electromyography

  • KeyboardArrowRight

    Management

    • Management overview

    • KeyboardArrowRight

      Recommendations

      • Recommendations overview

      • Canadian Consensus Working Group

      • European Atherosclerosis Society (EAS)

      • National Lipid Association (NLA) Statin Muscle Safety Task Force

      • American College of Cardiology/ American Heart Association (ACC/AHA)

    • Activity

    • KeyboardArrowRight

      Medications

      • Vitamin D

      • Coenzyme Q10

      • Creatine

    • Follow-up

    • Management of statin-associated autoimmune myopathy

  • KeyboardArrowRight

    Complications and Prognosis

    • Prognosis

  • KeyboardArrowRight

    Prevention and Screening

    • Prevention

    • Screening

  • KeyboardArrowRight

    Guidelines and Resources

    • KeyboardArrowRight

      Guidelines

      • United States guidelines

      • Canadian guidelines

      • European guidelines

    • Review articles

    • MEDLINE search

  • Patient Information

  • KeyboardArrowRight

    ICD Codes

    • ICD-10 codes

  • KeyboardArrowRight

    References

    • General references used

    • Recommendation grading systems used

    • Synthesized Recommendation Grading System for DynaMed

    • DynaMed Editorial Process

    • Special acknowledgements

    • How to cite

Topic Editor
Dhiren K. Patel PharmD
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Affiliations

Associate Professor of Pharmacology, Brown University, Alpert Medical School; Massachusetts, United States; Associate Professor of Pharmacy Practice, MCPHS University; Massachusetts, United States; Clinical Pharmacy Specialist and Certified Diabetes Educator, VA Boston Healthcare System; Massachusetts, United States

Conflicts of Interest

Dr. Patel declares no relevant financial conflicts of interest.

Recommendations Editor
Allen Shaughnessy PharmD, M Med Ed, FCCP
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Affiliations

Professor of Family Medicine and Director of Master Teacher Fellowship, Tufts University; Massachusetts, United States

Conflicts of Interest

Dr. Shaughnessy declares no relevant financial conflicts of interest.

Deputy Editor
Alexander Rae-Grant MD, FRCPC, FAAN
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Affiliations

Deputy Editor Neurology, DynaMed Plus; Massachusetts, United States; Neurologist, Cleveland Clinic; Ohio, United States

Conflicts of Interest

Dr. Rae-Grant declares no relevant financial conflicts of interest.

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