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Definitions of Statin-Associated Muscle Symptoms

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Statin-Associated Muscle Symptoms

Part of the book series: Contemporary Cardiology ((CONCARD))

Abstract

Statin-associated muscle symptoms (SAMS) have conventionally been termed “myopathy”; however, there is a spectrum of adverse muscle events that are not accurately described by this term. SAMS encompass myalgia (aches, pain, discomfort); myopathy (weakness); myositis (inflammation); and myonecrosis (elevated serum creatinine kinase levels). Precise clinical phenotypic definitions are essential in evaluating response to a statin or rechallenge with an alternative statin dosing regimen or statin agent. Multi-omic networks have been used to differentiate transcriptomic pathways that are activated in patients with myalgia and myopathy. Future efforts to identify biomarkers that increase the accuracy of nonspecific muscle symptoms or predict increased risk for SAMS require a uniform nomenclature.

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References

  1. Newman CB, Preiss D, Tobert JA, Jacobson TA, Page RL II, Goldstein LB, Chin C, Tannock LR, Miller M, Raghuveer G, Duell B, Brinton EA, Pollak A, Braun LT, Welty FK, American Heart Association Clinical Lipidology, Lipoprotein, Metabolism and Thrombosis Committee, a Joint Committee of the Council on Atherosclerosis, Thrombosis and Vascular Biology and Council on Lifestyle and Cardiometabolic Health, Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Stroke Council. Statin safety and associated adverse events: a scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol. 2019;39:e38–81.

    Article  CAS  Google Scholar 

  2. Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L, Gurwitz JH, Chan KA, Goodman MJ, Platt R. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA. 2004;292:2585–90.

    Article  CAS  Google Scholar 

  3. Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, Blumenthal R, Danesh J, Smith GD, DeMets D, Evans S, Law M, MacMahon S, Martin S, Neal B, Poulter N, Preiss D, Ridker P, Roberts I, Rodgers A, Sandercock P, Schulz K, Sever P, Simes J, Smeeth L, Wald N, Yusuf S, Peto R. Interpretation of the evidence for the efficacy and safety of statin therapy [published correction appears in Lancet. 2017;389:602]. Lancet. 2016;388:2532–61.

    Article  CAS  Google Scholar 

  4. Thompson PD, Clarkson P, Rosenson R. An assessment of statin safety by muscle experts. Am J Cardiol. 2006;97(Suppl 8A):69C–76C.

    Article  CAS  Google Scholar 

  5. Rosenson RS, Baker S, Jacobson T, Kopecky S, Parker B. An assessment of statin muscle safety task force: 2014 update. J Clin Lipidol. 2014;8:S58–71.

    Article  Google Scholar 

  6. Gupta A, Thompson D, Whitehouse A, Collier T, Dahlof B, Poulter N, Collins R, Sever P, ASCOT Investigators. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. 2017;389:2473–81.

    Article  CAS  Google Scholar 

  7. Newman CB, Tobert JA. Statin intolerance: reconciling clinical trials and clinical experience. JAMA. 2015;313:1011–2.

    Article  CAS  Google Scholar 

  8. Cohen JD, Brinton EA, Ito MK, Jacobson TA. Understanding Statin Use in America and Gaps in Patient Education (USAGE): an internet-based survey of 10,138 current and former statin users. J Clin Lipidol. 2012;6:208–15.

    Article  Google Scholar 

  9. Hill JA, Agewell S, Baranchuk A, Booz GW, Borer JC, Camici PG, Cehen PS, Bominiczak AF, Erol C,Grines C, Gropler RJ, Buzik TJ, Heinemann MK, Iskandrian AE, Knight BP, London B, Luscher TF, Metra M, Musunuru K, Nallamothu BK, Natale A, Saksena S, Picard MH, Rao SV, Remme WJ, Rosenson RS, Sweitzer NK, Timmis AD, Vrints CJ. Circulation. 2019. 10.1151/CIRCULATIONAHA.118.0039193 Circulation. 2019;139:571–2.

    Article  Google Scholar 

  10. Rosenson RS, Baker S, Banach M, Braun LT, Bruckert E, Brunham LR, Catapano AL, Elam MB, Mancini GBJ, Morris PB, Munter P, Ray KK, Stroes ES, Taylor BA, Taylor VH, Watts GF, Thompson P. Optimizing cholesterol treatment in patients with muscle complaints. J Am Coll Cardiol. 2017;70:1290–301.

    Article  Google Scholar 

  11. Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol. 2016;67:2395–410.

    Article  CAS  Google Scholar 

  12. Black HR, Quallich H, Gareleck CB. Racial differences in serum creatine kinase levels. Am J Med. 1986;81:479–87.

    Article  CAS  Google Scholar 

  13. Taylor BA, Panza G, Thompson PD. Increased creatine kinase with statin treatment may identify statin-associated muscle symptoms. Int J Cardiol. 2016;209:12–3.

    Article  Google Scholar 

  14. Parker BA, Capizzi JA, Grimaldi AS, Clarkson PM, Cole SM, Keadle J, Chipkin S, Pescatello LS, Simpson K, White CM, Thompson PD. Effect of statins on skeletal muscle function. Circulation. 2013;127:96–103.

    Article  CAS  Google Scholar 

  15. Taylor BA, Lorson L, White CM, Thompson PD. A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy. Atherosclerosis. 2015;238:329–35.

    Article  CAS  Google Scholar 

  16. Nissen SE, Sroes E, Dent-Acosta RE, Rosenson RS, Lehman S, Sattar N, Preiss D, Bruckert E, Češka R, Lepor N, Ballantyne CM, Gouni-Berthold I, Elliott M, Brennan DM, Wasserman SM, Somaratne R, Scott R, Stein EA, GAUSS-3 Investigators. Efficacy and tolerability of evolocumab vs. ezetimibe in patients with muscle-related statin intolerance documented by placebo-controlled atorvastatin rechallenge: the GAUSS-3 randomized clinical trial. JAMA. 2016;315:1580–90.

    Article  CAS  Google Scholar 

  17. Mefford MM, Burkholder G, Farkouh M, Muntner P, Rosenson RS. Willingness to be re-initiated on a statin (from the REasons for Geographic and Racial Differences in Stroke [REGARDS] Study). Am J Cardiol. 2018;122:768–74.

    Article  Google Scholar 

  18. Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, Roden M, Stein E, Tokgözoğlu L, Nordestgaard BG, Bruckert E, De Backer G, Krauss RM, Laufs U, Santos RD, Hegele RA, Hovingh GK, Leiter LA, Mach F, März W, Newman CB, Wiklund O, Jacobson TA, Catapano AL, Chapman MJ, Ginsberg HN, European Atherosclerosis Society Consensus Panel. Statin-associated muscle symptoms: impact on statin therapy. European Atherosclerosis Society consensus panel statement on assessment, aetiology and management. Eur Heart J. 2015;36:1012–22.

    Article  CAS  Google Scholar 

  19. Mancini GB, Tashakkor AY, Baker S, Bergeron J, Fitchett D, Frohlich J, et al. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Working Group Consensus update. Can J Cardiol. 2013;29:1553–68.

    Article  Google Scholar 

  20. Pasternak RC, Smith SC Jr, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C, American College of Cardiology, American Heart Association, National Heart, Lung and Blood Institute. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. J Am Coll Cardiol. 2002;40:567–72.

    Article  Google Scholar 

  21. Brunham LR, Baker S, Mammen A, Mancini GBJ, Rosenson RS. Role of genetics in the prediction of statin associated muscle symptoms and optimization of statin use and adherence. Cardiovasc Res. 2018;114:1073–81.

    Article  CAS  Google Scholar 

  22. Elam MB, Majumdar G, Mozhui K, Gerling IC, Vera SR, Fish-Trotter H, Williams RW, Childress RD, Raghow R. Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge. PLoS One. 2017;12:e0181308. https://doi.org/10.1371/journal.pone.0181308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rosenson RS, Miller K, Bayliss M, Sanchez R, Baccara-Dinet M, Chibedi-De-Roche D, Taylor B, Khan I, Manvelian G, Whilte M, Jacobson TA. The Statin Myalgia Clinical Index (SMCI): revision for clinical use, content validation, and inter-rater reliability. Cardiovasc Drugs Ther. 2017;31:179–86.

    Article  Google Scholar 

  24. Taylor BA, Sanchez RJ, Jacobson TA, De-Roche C, Manvelian G, Baccara-Dinet MT, Khan I, Rosenson RS. Application of the statin associated muscle symptoms-clinical index to a randomized trial on statin myopathy. J Am Coll Cardiol. 2017;70:1680–1.

    Article  Google Scholar 

  25. Colantonio LD, Kent ST, Huang L, Chen L, Monda KL, Serban MC, Manthrigragada A, Kilgore ML, Rosenson RS, Munter P. Algorithms to identify statin intolerance in Medicare administrative claim data. Cardiovasc Drugs Ther. 2016;30:525–33.

    Article  Google Scholar 

  26. Serban MC, Colantonio LD, Manthripragada A, Monda KL, Bittner V, Banch M, Chen L, Huang L, Dent R, Kent ST, Munter P, Rosenson RS. Statin intolerance and risk for recurrent myocardial infarction, coronary heart disease events and all-cause mortality following hospital discharge after myocardial infarction among Medicare beneficiaries. J Am Coll Cardiol. 2017;69:1386–95.

    Article  CAS  Google Scholar 

  27. Zhang H, Plutzky J, Shubina M, Turchin A. Continued statin prescriptions after adverse reactions and patient outcomes: a cohort study. Ann Intern Med. 2017;167:221–7.

    Article  Google Scholar 

  28. Rodriguez F, Maron DJ, Knowles JW, Virani SS, Lin S, Heidenreich PA. Association of statin adherence with mortality in patients with atherosclerotic cardiovascular disease. JAMA Cardiol. 2019;4:206. https://doi.org/10.1001/jamacardio.2018.4936.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Zena and Michael A Wiener Cardiovascular Institute, Marie-Josee and Henry R. Kravis Center for Cardiovascular Health, Mount Sinai Hospital, New York, NY, USA

    Robert S. Rosenson

  2. Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Robert S. Rosenson

  3. The Lauder Family Cardiovascular Ambulatory Center, New York, NY, USA

    Robert S. Rosenson

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Correspondence to Robert S. Rosenson .

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Editors and Affiliations

  1. Hartford Hospital, University of Connecticut, Hartford, CT, USA

    Paul D. Thompson

  2. Hartford Hospital, University of Connecticut, Hartford, CT, USA

    Beth A. Taylor

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Rosenson, R.S. (2020). Definitions of Statin-Associated Muscle Symptoms. In: Thompson, P., Taylor, B. (eds) Statin-Associated Muscle Symptoms. Contemporary Cardiology. Springer, Cham. https://doi.org/10.1007/978-3-030-33304-1_4

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  • DOI: https://doi.org/10.1007/978-3-030-33304-1_4

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-33303-4

  • Online ISBN: 978-3-030-33304-1

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