Current Atherosclerosis Reports

, Volume 12, Issue 5, pp 322–330 | Cite as

Evidence-Based Management of Statin Myopathy

  • Charles R. Harper
  • Terry A. Jacobson


Statin-associated muscle symptoms are a relatively common condition that may affect 10% to 15% of statin users. Statin myopathy includes a wide spectrum of clinical conditions, ranging from mild myalgia to rhabdomyolysis. The etiology of myopathy is multifactorial. Recent studies suggest that statins may cause myopathy by depleting isoprenoids and interfering with intracellular calcium signaling. Certain patient and drug characteristics increase risk for statin myopathy, including higher statin doses, statin cytochrome metabolism, and polypharmacy. Genetic risk factors have been identified, including a single nucleotide polymorphism of SLCO1B1. Coenzyme Q10 and vitamin D have been used to prevent and treat statin myopathy; however, clinical trial evidence demonstrating their efficacy is limited. Statin-intolerant patients may be successfully treated with either low-dose statins, alternate-day dosing, or using twice-weekly dosing with longer half-life statins. An algorithm is presented to assist the clinician in managing myopathy in patients with dyslipidemia.


Myalgia Myopathy Muscle symptoms Statin Fibrates Drug safety Rhabdomyolysis Algorithm Drug interactions Myositis Coenzyme Q 10 Red yeast rice Creatine kinase Cholesterol Management Lipids Vitamin D Cytochrome metabolism Ezetimibe Colesevelam 



No potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Law M, Rudnicka AR: Statin safety: a systematic review. Am J Cardiol 2006, 97:52C–60C.CrossRefPubMedGoogle Scholar
  2. 2.
    Mitka M: Expanding statin use to help more at-risk patients is causing financial heartburn. JAMA 2003, 290:2243–2245.CrossRefPubMedGoogle Scholar
  3. 3.
    Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al.: ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. Circulation 2002, 106:1024–1028.CrossRefPubMedGoogle Scholar
  4. 4.
    McKenney JM, Davidson MH, Jacobson TA, Guyton JR, National Lipid Association Statin Safety Assessment Task Force: Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol 2006, 97:89C–94C.CrossRefPubMedGoogle Scholar
  5. 5.
    Harper CR, Jacobson TA: The broad spectrum of statin myopathy: from myalgia to rhabdomyolysis. Curr Opin Lipidol 2007, 18:401–408.CrossRefPubMedGoogle Scholar
  6. 6.
    Gaist D, Rodriguez LA, Huerta C, et al.: Lipid-lowering drugs and risk of myopathy: a population-based follow-up study. Epidemiology 2001, 12:565–569.CrossRefPubMedGoogle Scholar
  7. 7.
    Shanahan RL, Kerzee JA, Sandhoff BG, et al.: Low myopathy rates associated with statins as monotherapy or combination therapy with interacting drugs in a group model health maintenance organization. Pharmacotherapy 2005, 25:345–351.CrossRefPubMedGoogle Scholar
  8. 8.
    Bruckert E, Hayem G, Dejager S, et al.: Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study [see comment]. Cardiovasc Drugs Ther 2005, 19:403–414.CrossRefPubMedGoogle Scholar
  9. 9.
    Mohaupt MG, Karas RH, Babiychuk EB, et al.: Association between statin-associated myopathy and skeletal muscle damage. CMAJ Can Med Assoc J 2009, 181:E11–E18.CrossRefGoogle Scholar
  10. 10.
    Hodel C: Myopathy and rhabdomyolysis with lipid-lowering drugs. Toxicol Lett 2002, 128:159–168.CrossRefPubMedGoogle Scholar
  11. 11.
    Flint OP, Masters BA, Gregg RE, Durham SK: Inhibition of cholesterol synthesis by squalene synthase inhibitors does not induce myotoxicity in vitro. Toxicol Appl Pharmacol 1997, 145:91–98.CrossRefPubMedGoogle Scholar
  12. 12.
    Baker SK: Molecular clues into the pathogenesis of statin-mediated muscle toxicity. Muscle Nerve 2005, 31:572–580.CrossRefPubMedGoogle Scholar
  13. 13.
    Marcoff L, Thompson PD: The role of coenzyme Q10 in statin-associated myopathy: a systematic review [see comment]. J Am Coll Cardiol 2007, 49:2231–2237.CrossRefPubMedGoogle Scholar
  14. 14.
    Baer AN, Wortmann RL: Myotoxicity associated with lipid-lowering drugs. Curr Opin Rheumatol 2007, 19:67–73.PubMedGoogle Scholar
  15. 15.
    Päivä H, Thelen KM,Van Coster R, et al.: High-dose statins and skeletal muscle metabolism in humans: a randomized, controlled trial. Clin Pharmacol Ther 2005, 78:60–68.CrossRefPubMedGoogle Scholar
  16. 16.
    Laaksonen R, Jokelainen K, Sahi T, et al.: Decreases in serum ubiquinone concentrations do not result in reduced levels in muscle tissue during short-term simvastatin treatment in humans. Clin Pharmacol Ther 1995, 57:62–66.CrossRefPubMedGoogle Scholar
  17. 17.
    Schaefer WH, Lawrence JW, Loughlin AF, et al.: Evaluation of ubiquinone concentration and mitochondrial function relative to cerivastatin-induced skeletal myopathy in rats. Toxicol Appl Pharmacol 2004, 194:10–23.CrossRefPubMedGoogle Scholar
  18. 18.
    Dirks AJ, Jones KM: Statin-induced apoptosis and skeletal myopathy. Am J Physiol Cell Physiol 2006, 291:C1208–1212.CrossRefPubMedGoogle Scholar
  19. 19.
    Guijarro C, Blanco-Colio LM, Ortego M, et al.: 3-Hydroxy-3-methylglutaryl coenzyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture. Circ Res 1998, 83:490–500.PubMedGoogle Scholar
  20. 20.
    Sirvent P, Mercier J, Vassort G, Lacampagne A: Simvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle. Biochem Biophys Res Commun 2005, 329:1067–1075.CrossRefPubMedGoogle Scholar
  21. 21.
    Toth PP, Harper CR, Jacobson TA: Clinical characterization and molecular mechanisms of statin myopathy. Expert Rev Cardiovasc Ther 2008, 6:955–969.CrossRefPubMedGoogle Scholar
  22. 22.
    Brewer HB Jr: Benefit-risk assessment of rosuvastatin 10 to 40 milligrams. Am J Cardiol 2003, 92:23 K–29 K.CrossRefPubMedGoogle Scholar
  23. 23.
    •• Jacobson TA: Toward “pain-free” statin prescribing: clinical algorithm for diagnosis and management of myalgia [see comment]. Mayo Clin Proc 2008, 83:687–700. This is an excellent overview of statin-induced myalgia with one of the first published algorithms on myalgia management strategies.Google Scholar
  24. 24.
    Venero CV, Thompson PD: Managing statin myopathy. Endocrinol Metab Clin North Am 2009, 38:121–136.CrossRefPubMedGoogle Scholar
  25. 25.
    Vladutiu GD, Simmons Z, Isackson PJ, et al.: Genetic risk factors associated with lipid-lowering drug-induced myopathies. Muscle Nerve 2006, 34:153–162.CrossRefPubMedGoogle Scholar
  26. 26.
    •• Group SC, Link E, Parish S, et al.: SLCO1B1 variants and statin-induced myopathy--a genomewide study [see comment]. N Engl J Med 2008, 359:789–799. This was one of the first studies to identify genetic predictors of myopathy, such as specific defects in the statin organic anion transporting polypeptide system responsible for hepatic uptake of statins.Google Scholar
  27. 27.
    Harper CR, Jacobson TA: Managing dyslipidemia in chronic kidney disease. J Am Coll Cardiol 2008, 51:2375–2384.CrossRefPubMedGoogle Scholar
  28. 28.
    Graham DJ, Staffa JA, Shatin D, et al.: Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 2004, 292:2585–2590.CrossRefPubMedGoogle Scholar
  29. 29.
    Jones PH, Davidson MH: Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol 2005, 95:120–122.CrossRefPubMedGoogle Scholar
  30. 30.
    Prueksaritanont T, Zhao JJ, Ma B, et al.: Mechanistic studies on metabolic interactions between gemfibrozil and statins. J Pharmacol Exp Ther 2002, 301:1042–1051.CrossRefPubMedGoogle Scholar
  31. 31.
    Caso G, Kelly P, McNurlan MA, Lawson WE: Effect of coenzyme q10 on myopathic symptoms in patients treated with statins. Am J Cardiol 2007, 99:1409–1412.CrossRefPubMedGoogle Scholar
  32. 32.
    Young JM, Florkowski CM, Molyneux SL, et al.: Effect of coenzyme Q(10) supplementation on simvastatin-induced myalgia. Am J Cardiol 2007, 100:1400–1403.CrossRefPubMedGoogle Scholar
  33. 33.
    Lips P: Vitamin D physiology. Prog Biophys Mol Biol 2006, 92:4–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Bischoff-Ferrari HA, Dietrich T, Orav EJ, et al.: Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or =60 y. Am J Clin Nutr 2004, 80:752–758.PubMedGoogle Scholar
  35. 35.
    Erkal MZ, Wilde J, Bilgin Y, et al.: High prevalence of vitamin D deficiency, secondary hyperparathyroidism and generalized bone pain in Turkish immigrants in Germany: identification of risk factors. Osteoporos Int 2006, 17:1133–1140.CrossRefPubMedGoogle Scholar
  36. 36.
    Ahmed W, Khan N, Glueck CJ, et al.: Low serum 25 (OH) vitamin D levels (<32 ng/mL) are associated with reversible myositis-myalgia in statin-treated patients. Transl Res 2009, 153:11–16.CrossRefPubMedGoogle Scholar
  37. 37.
    Gazi IF, Daskalopoulou SS, Nair DR, Mikhailidis DP: Effect of ezetimibe in patients who cannot tolerate statins or cannot get to the low density lipoprotein cholesterol target despite taking a statin. Curr Med Res Opin 2007, 23:2183–2192.CrossRefPubMedGoogle Scholar
  38. 38.
    Stein EA, Ballantyne CM, Windler E, et al.: Efficacy and tolerability of fluvastatin XL 80 mg alone, ezetimibe alone, and the combination of fluvastatin XL 80 mg with ezetimibe in patients with a history of muscle-related side effects with other statins. Am J Cardiol 2008, 101:490–496.CrossRefPubMedGoogle Scholar
  39. 39.
    Backes JM, Venero CV, Gibson CA, et al.: Effectiveness and tolerability of every-other-day rosuvastatin dosing in patients with prior statin intolerance. Ann Pharmacother 2008, 42:34–346.Google Scholar
  40. 40.
    Athyros VG, Tziomalos K, Kakafika AI, et al.: Effectiveness of ezetimibe alone or in combination with twice a week Atorvastatin (10 mg) for statin intolerant high-risk patients. Am J Cardiol 2008, 101:483–485.CrossRefPubMedGoogle Scholar
  41. 41.
    Rivers SM, Kane MP, Busch RS, et al.: Colesevelam hydrochloride-ezetimibe combination lipid-lowering therapy in patients with diabetes or metabolic syndrome and a history of statin intolerance. Endocr Pract 2007, 13:11–16.PubMedGoogle Scholar
  42. 42.
    Lu Z, Kou W, Du B, et al.: Effect of Xuezhikang, an extract from red yeast Chinese rice, on coronary events in a Chinese population with previous myocardial infarction. Am J Cardiol 2008, 101:1689–1693.CrossRefPubMedGoogle Scholar
  43. 43.
    Becker DJ, Gordon RY, Halbert SC, et al.: Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized trial [see comment]. [summary for patients in Ann Intern Med. 2009 Jun 16;150(12):I28; PMID: 19528545]. Ann Intern Med 2009, 150:830–839.Google Scholar
  44. 44.
    Guyton JR: Benefit versus risk in statin treatment. Am J Cardiol 2006, 97:95C–97C.CrossRefPubMedGoogle Scholar
  45. 45.
    Wilt TJ, Bloomfield HE, MacDonald R, et al.: Effectiveness of statin therapy in adults with coronary heart disease. Arch Intern Med 2004, 164:1427–1436.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of MedicineEmory UniversityAtlantaUSA
  2. 2.Office of Health Promotion and Disease PreventionEmory UniversityAtlantaUSA

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