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  • Review Article
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Safety and efficacy of statin therapy

Nature Reviews Cardiology volume 15, pages 757–769 (2018)Cite this article

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Abstract

The 2013 ACC/AHA guidelines on blood cholesterol management were a major shift in the delineation of the main patient groups that could benefit from statin therapy and emphasized the use of higher-intensity statin therapies. In 2016, an expert consensus panel from the ACC recommended the use of nonstatin therapies (ezetimibe and PCSK9 inhibitors) in addition to maximally tolerated statin therapy in individuals whose LDL-cholesterol and non-HDL-cholesterol levels remained above certain thresholds after statin treatment. Given the substantial benefits of statin therapies in both primary and secondary prevention of cardiovascular disease, their long-term safety has become a concern. The potential harmful effects of statin therapy on muscle and liver have been known for some time, but new concerns have emerged regarding the risk of new-onset diabetes mellitus, cognitive impairment and haemorrhagic stroke associated with the use of statins and the risks of achieving very low levels of LDL cholesterol. The increased media attention on the adverse events associated with statins has unfortunately led to statin therapy discontinuation, nonadherence to therapy or concerns about initiating statin therapy. In this Review, we explore the safety of statin therapy in light of the latest evidence and provide clinicians with reassurance about the safety of statins. Overwhelming evidence suggests that the benefits of statin therapy far outweigh any real or perceived risks.

Key points

  • Moderate-intensity and high-intensity statin therapy has demonstrated benefits in reducing the risk of atherosclerotic cardiovascular disease in both primary and secondary prevention.

  • The most commonly reported adverse effects of statins are statin-associated muscle symptoms (SAMS), but whether these symptoms are caused by statin pharmacological effects or by nocebo effects is controversial.

  • The clinical tool SAMS-Clinical Index (SAMS-CI) might help clinicians to assess SAMS.

  • Although hepatotoxicity has been a previous concern when using statin therapy, data suggest that statins are safe and that levels of liver enzymes do not need to be checked routinely.

  • Other known adverse effects of statins include a small increase in the risk of diabetes mellitus and a possible increase in haemorrhagic stroke in patients who have had a previous stroke.

  • Although concerns have been raised about reaching very low levels of LDL cholesterol, data from trials on PCSK9 inhibitors suggest that low LDL-cholesterol levels are safe.

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Fig. 1: Clinical benefits and potential adverse effects of statin therapy.

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References

  1. Stone, N. J. et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol. 63, 2889–2934 (2014).

    PubMed  Google Scholar 

  2. Baigent, C. et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 366, 1267–1278 (2005).

    CAS  PubMed  Google Scholar 

  3. Cholesterol Treatment Trialists Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376, 1670–1681 (2010).

    Google Scholar 

  4. Collins, R. et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet 388, 2532–2561 (2016).

    CAS  PubMed  Google Scholar 

  5. Cannon, C. P. et al. Ezetimibe added to statin therapy after acute coronary syndromes. N. Engl. J. Med. 372, 2387–2397 (2015).

    CAS  PubMed  Google Scholar 

  6. Sabatine, M. S. et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med. 376, 1713–1722 (2017).

    CAS  PubMed  Google Scholar 

  7. Adhyaru, B. B. & Jacobson, T. A. Role of non-statins, LDL-C thresholds, and special population considerations: a look at the updated 2016 ACC Consensus Committee Recommendations. Curr. Atheroscler. Rep. 19, 29 (2017).

    PubMed  Google Scholar 

  8. Writing Committee. et al. 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Task Force on Clinical Expert Consensus documents. J. Am. Coll. Cardiol. 68, 92–125 (2016).

    Google Scholar 

  9. Lloyd-Jones, D. M. et al. 2017 focused update of the 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J. Am. Coll. Cardiol. 70, 1785–1822 (2017).

    PubMed  Google Scholar 

  10. Cannon, C. P. et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N. Engl. J. Med. 350, 1495–1504 (2004).

    CAS  PubMed  Google Scholar 

  11. LaRosa, J. C. et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N. Engl. J. Med. 352, 1425–1435 (2005).

    CAS  PubMed  Google Scholar 

  12. Pedersen, T. R. et al. High-dose atorvastatin versus usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 294, 2437–2445 (2005).

    CAS  PubMed  Google Scholar 

  13. de Lemos, J. A. et al. Early intensive versus a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 292, 1307–1316 (2004).

    PubMed  Google Scholar 

  14. Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet 376, 1658–1669 (2010).

    Google Scholar 

  15. Cholesterol Treatment Trialists Collaboration. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet 380, 581–590 (2012).

    Google Scholar 

  16. Kjekshus, J. et al. Rosuvastatin in older patients with systolic heart failure. N. Engl. J. Med. 357, 2248–2261 (2007).

    CAS  PubMed  Google Scholar 

  17. Tavazzi, L. et al. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 372, 1231–1239 (2008).

    PubMed  Google Scholar 

  18. Baigent, C. et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet 377, 2181–2192 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Fellstrom, B. C. et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N. Engl. J. Med. 360, 1395–1407 (2009).

    CAS  PubMed  Google Scholar 

  20. Wanner, C. et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N. Engl. J. Med. 353, 238–248 (2005).

    CAS  PubMed  Google Scholar 

  21. Bruckert, E., Hayem, G., Dejager, S., Yau, C. & Begaud, B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients — the PRIMO study. Cardiovasc. Drugs Ther. 19, 403–414 (2005).

    CAS  PubMed  Google Scholar 

  22. Cohen, J. D., Brinton, E. A., Ito, M. K. & Jacobson, T. A. 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. 6, 208–215 (2012).

    PubMed  Google Scholar 

  23. Colantonio, L. D. et al. Adherence to high-intensity statins following a myocardial infarction hospitalization among medicare beneficiaries. JAMA Cardiol. 2, 890–895 (2017).

    PubMed  PubMed Central  Google Scholar 

  24. Rosenson, R. S. et al. An assessment by the Statin Muscle Safety Task Force: 2014 update. J. Clin. Lipidol. 8, S58–71 (2014).

    PubMed  Google Scholar 

  25. Mancini, G. B. et al. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Consensus Working Group update. Can. J. Cardiol. 32, S35–S65 (2016).

    PubMed  Google Scholar 

  26. Stroes, E. S. et al. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur. Heart J. 36, 1012–1022 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Awad, K. et al. Efficacy and Safety of alternate-day versus daily dosing of statins: a systematic review and meta-analysis. Cardiovasc. Drugs Ther. 31, 419–431 (2017).

    CAS  PubMed  Google Scholar 

  28. Parker, B. A. et al. Effect of statins on skeletal muscle function. Circulation 127, 96–103 (2013).

    CAS  PubMed  Google Scholar 

  29. Rosenson, R. S. et al. The statin-associated muscle symptom clinical index (SAMS-CI): revision for clinical use, content validation, and inter-rater reliability. Cardiovasc. Drugs Ther. 31, 179–186 (2017).

    PubMed  PubMed Central  Google Scholar 

  30. Taylor, B. A. et al. Application of the statin-associated muscle symptoms-clinical index to a randomized trial on statin myopathy. J. Am. Coll. Cardiol. 70, 1680–1681 (2017).

    PubMed  Google Scholar 

  31. Schech, S. et al. Risk factors for statin-associated rhabdomyolysis. Pharmacoepidemiol. Drug Saf. 16, 352–358 (2007).

    CAS  PubMed  Google Scholar 

  32. Banach, M. et al. Statin intolerance — an attempt at a unified definition. Position paper from an International Lipid Expert Panel. Expert Opin. Drug Saf. 14, 935–955 (2015).

    CAS  PubMed  Google Scholar 

  33. Abd, T. T. & Jacobson, T. A. Statin-induced myopathy: a review and update. Expert Opin. Drug Saf. 10, 373–387 (2011).

    CAS  PubMed  Google Scholar 

  34. Guengerich, F. P. Cytochrome P450 and chemical toxicology. Chem. Res. Toxicol. 21, 70–83 (2008).

    CAS  PubMed  Google Scholar 

  35. Bellosta, S. & Corsini, A. Statin drug interactions and related adverse reactions. Expert Opin. Drug Saf. 11, 933–946 (2012).

    CAS  PubMed  Google Scholar 

  36. Gupta, A. et al. 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 389, 2473–2481 (2017).

    CAS  PubMed  Google Scholar 

  37. Sever, P. S. et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 361, 1149–1158 (2003).

    CAS  PubMed  Google Scholar 

  38. Adhyaru, B. B. & Jacobson, T. A. Unblinded ASCOT study results do not rule out that muscle symptoms are an adverse effect of statins. Evid. Based Med. 22, 210 (2017).

    PubMed  Google Scholar 

  39. Nissen, S. E. et al. Efficacy and tolerability of evolocumab versus ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial. JAMA 315, 1580–1590 (2016).

    CAS  PubMed  Google Scholar 

  40. Mampuya, W. M. et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience. Am. Heart J. 166, 597–603 (2013).

    PubMed  PubMed Central  Google Scholar 

  41. Jacobson, T. A., Khan, A., Maki, K. C., Brinton, E. A. & Cohen, J. D. Provider recommendations for patient-reported muscle symptoms on statin therapy: insights from the understanding statin use in America and gaps in patient education survey. J. Clin. Lipidol. 12, 78–88 (2018).

    PubMed  Google Scholar 

  42. Banach, M. et al. Statin intolerance — an attempt at a unified definition. Position paper from an International Lipid Expert Panel. Arch. Med. Sci. 11, 1–23 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Guyton, J. R., Bays, H. E., Grundy, S. M. & Jacobson, T. A., The National Lipid Association Statin Intolerance Panel. An assessment by the Statin Intolerance Panel: 2014 update. J. Clin. Lipidol. 8, S72–S81 (2014).

    PubMed  Google Scholar 

  44. Graham, J. H. et al. Clinical and economic consequences of statin intolerance in the United States: results from an integrated health system. J. Clin. Lipidol. 11, 70–79 (2017).

    PubMed  Google Scholar 

  45. Athyros, V. G. 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. 101, 483–485 (2008).

    CAS  PubMed  Google Scholar 

  46. Moriarty, P. M. et al. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J. Clin. Lipidol. 8, 554–561 (2014).

    PubMed  Google Scholar 

  47. Orringer, C. E. et al. Update on the use of PCSK9 inhibitors in adults: recommendations from an Expert Panel of the National Lipid Association. J. Clin. Lipidol. 11, 880–890 (2017).

    PubMed  Google Scholar 

  48. Ridker, P. M. et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N. Engl. J. Med. 359, 2195–2207 (2008).

    CAS  PubMed  Google Scholar 

  49. Sattar, N. et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 375, 735–742 (2010).

    CAS  PubMed  Google Scholar 

  50. Ridker, P. M., Pradhan, A., MacFadyen, J. G., Libby, P. & Glynn, R. J. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet 380, 565–571 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Amarenco, P. et al. High-dose atorvastatin after stroke or transient ischemic attack. N. Engl. J. Med. 355, 549–559 (2006).

    CAS  PubMed  Google Scholar 

  52. Preiss, D. et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 305, 2556–2564 (2011).

    CAS  PubMed  Google Scholar 

  53. Swerdlow, D. I. et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet 385, 351–361 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Giugliano, R. P. et al. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet 390, 1962–1971 (2017).

    CAS  PubMed  Google Scholar 

  55. Schmidt, A. F. et al. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study. Lancet Diabetes Endocrinol. 5, 97–105 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Bays, H., Cohen, D. E., Chalasani, N. & Harrison, S. A., The National Lipid Association’s Statin Safety Task Force. An assessment by the Statin Liver Safety Task Force: 2014 update. J. Clin. Lipidol. 8, S47–S57 (2014).

    PubMed  Google Scholar 

  57. Herrick, C., Bahrainy, S. & Gill, E. A. Statins and the liver. Cardiol. Clin. 33, 257–265 (2015).

    PubMed  Google Scholar 

  58. Henderson, L. M., Patel, S., Giordano, T. P., Green, L. & El-Serag, H. B. Statin therapy and serum transaminases among a cohort of HCV-infected veterans. Dig. Dis. Sci. 55, 190–195 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Gomez-Dominguez, E., Gisbert, J. P., Moreno-Monteagudo, J. A., Garcia-Buey, L. & Moreno-Otero, R. A pilot study of atorvastatin treatment in dyslipemid, non-alcoholic fatty liver patients. Aliment. Pharmacol. Ther. 23, 1643–1647 (2006).

    CAS  PubMed  Google Scholar 

  60. Hyogo, H. et al. Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia. Metabolism 57, 1711–1718 (2008).

    CAS  PubMed  Google Scholar 

  61. Motamed, N. et al. Non-alcoholic fatty liver disease (NAFLD) and 10-year risk of cardiovascular diseases. Clin. Res. Hepatol. Gastroenterol. 41, 31–38 (2017).

    PubMed  Google Scholar 

  62. Athyros, V. G. et al. Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis. Lancet 376, 1916–1922 (2010).

    CAS  PubMed  Google Scholar 

  63. Parekh, J., Corley, D. A. & Feng, S. Diabetes, hypertension and hyperlipidemia: prevalence over time and impact on long-term survival after liver transplantation. Am. J. Transplant. 12, 2181–2187 (2012).

    CAS  PubMed  Google Scholar 

  64. Martin, J. E. et al. Incidence of adverse events with HMG-CoA reductase inhibitors in liver transplant patients. Clin. Transplant. 22, 113–119 (2008).

    PubMed  Google Scholar 

  65. Wiggins, B. S. et al. Recommendations for management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease: a scientific statement from the American Heart Association. Circulation 134, e468–e495 (2016).

    PubMed  Google Scholar 

  66. Cash, W. J. et al. Randomized controlled trial assessing the effect of simvastatin in primary biliary cirrhosis. Liver Int. 33, 1166–1174 (2013).

    CAS  PubMed  Google Scholar 

  67. Rojas-Fernandez, C. H. et al. An assessment by the Statin Cognitive Safety Task Force: 2014 update. J. Clin. Lipidol. 8, S5–S16 (2014).

    PubMed  Google Scholar 

  68. Petersen, R. C. Clinical practice. Mild cognitive impairment. N. Engl. J. Med. 364, 2227–2234 (2011).

    CAS  PubMed  Google Scholar 

  69. Nasreddine, Z. S. et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J. Am. Geriatr. Soc. 53, 695–699 (2005).

    PubMed  Google Scholar 

  70. Robert, P. et al. Review of Alzheimer’s disease scales: is there a need for a new multi-domain scale for therapy evaluation in medical practice? Alzheimers Res. Ther. 2, 24 (2010).

    PubMed  PubMed Central  Google Scholar 

  71. Ott, B. R. et al. Do statins impair cognition? A systematic review and meta-analysis of randomized controlled trials. J. Gen. Intern. Med. 30, 348–358 (2015).

    PubMed  PubMed Central  Google Scholar 

  72. Shepherd, J. et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360, 1623–1630 (2002).

    CAS  PubMed  Google Scholar 

  73. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360, 23–33 (2002).

    Google Scholar 

  74. Trompet, S. et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J. Neurol. 257, 85–90 (2010).

    CAS  PubMed  Google Scholar 

  75. Goldstein, L. B. et al. Hemorrhagic stroke in the stroke prevention by aggressive reduction in cholesterol levels study. Neurology 70, 2364–2370 (2008).

    CAS  PubMed  Google Scholar 

  76. Hackam, D. G. et al. Statins and intracerebral hemorrhage: collaborative systematic review and meta-analysis. Circulation 124, 2233–2242 (2011).

    CAS  PubMed  Google Scholar 

  77. Giugliano, R. P. et al. Long-term safety and efficacy of achieving very low levels of low-density lipoprotein cholesterol: a prespecified analysis of the IMPROVE-IT trial. JAMA Cardiol. 2, 547–555 (2017).

    PubMed  PubMed Central  Google Scholar 

  78. Hsia, J., MacFadyen, J. G., Monyak, J. & Ridker, P. M. Cardiovascular event reduction and adverse events among subjects attaining low-density lipoprotein cholesterol <50 mg/dl with rosuvastatin. The JUPITER trial (justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin). J. Am. Coll. Cardiol. 57, 1666–1675 (2011).

    CAS  PubMed  Google Scholar 

  79. Hess, C. N., Low Wang, C. C. & Hiatt, W. R. PCSK9 inhibitors: mechanisms of action, metabolic effects, and clinical outcomes. Annu. Rev. Med. 69, 133–145 (2018).

    CAS  PubMed  Google Scholar 

  80. Robinson, J. G. et al. Safety of very low low-density lipoprotein cholesterol levels with alirocumab: pooled data from randomized trials. J. Am. Coll. Cardiol. 69, 471–482 (2017).

    CAS  PubMed  Google Scholar 

  81. Schwartz, G. G. et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am. Heart J. 168, 682–689 (2014).

    CAS  PubMed  Google Scholar 

  82. Rosenson, R. S. et al. Optimizing cholesterol treatment in patients with muscle complaints. J. Am. Coll. Cardiol. 70, 1290–1301 (2017).

    PubMed  Google Scholar 

  83. Collins, R. et al. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 361, 2005–2016 (2003).

    PubMed  Google Scholar 

  84. Freeman, D. J. et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 103, 357–362 (2001).

    CAS  PubMed  Google Scholar 

  85. Keech, A. et al. Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose: results from the LIPID trial. Diabetes Care 26, 2713–2721 (2003).

    CAS  PubMed  Google Scholar 

  86. Nakamura, H. et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet 368, 1155–1163 (2006).

    CAS  PubMed  Google Scholar 

  87. Downs, J. R. et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 279, 1615–1622 (1998).

    CAS  PubMed  Google Scholar 

  88. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344, 1383–1389 (1994).

    Google Scholar 

  89. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin versus usual care: The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT-LLT). JAMA 288, 2998–3007 (2002).

    Google Scholar 

  90. GISSI Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico). Results of the low-dose (20 mg) pravastatin GISSI Prevenzione trial in 4271 patients with recent myocardial infarction: do stopped trials contribute to overall knowledge? Ital. Heart J. 1, 810–820 (2000).

    Google Scholar 

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Acknowledgements

Review criteria

We conducted a literature search using Medline, PubMed and Embase and limited the search to the years 2000–2017. Search terms included “statin adverse effects”, “statin safety”, “statin side effects” and “statin intolerance”. In addition, search terms related to specific target organs and adverse events were also used, including “statin AND muscle, diabetes, glucose, cognitive function and stroke”. Publications were fully reviewed if the abstract suggested that the study was relevant and used only human data.

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Authors and Affiliations

  1. Division of General Internal Medicine & Geriatrics, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Bhavin B. Adhyaru & Terry A. Jacobson

  2. Lipid Clinic and Cardiovascular Risk Reduction Program, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Terry A. Jacobson

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Both authors researched data for the article, contributed to the discussion of content, and wrote, reviewed and edited the manuscript before submission.

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Correspondence to Bhavin B. Adhyaru or Terry A. Jacobson.

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T.A.J. is a consultant for Amgen and Regeneron/Sanofi. B.B.A. declares no competing interests.

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Glossary

Statin-associated muscle symptoms

(SAMS). Muscle symptoms that are the most prevalent adverse effect reported with statin therapy.

Statin intolerance

A clinical syndrome characterized by the inability to tolerate multiple statins with either objectionable symptoms or abnormal laboratory determinations that are temporally related to statin treatment and reversible upon statin discontinuation but reproducible by rechallenge.

Creatine kinase

An enzyme that is found in skeletal muscle, the heart, and the brain, and increases in the blood due to muscle injury, inflammation or necrosis of skeletal or heart muscle.

Myalgia

A condition involving muscle aches, stiffness, soreness, tenderness or cramps.

Rhabdomyolysis

A rare, life-threatening condition, characterized by the rapid destruction of skeletal muscle typically with creatine kinase levels >10 times the upper limit of normal and which often leads to acute renal failure.

Statin-induced necrotizing autoimmune myopathy

(SINAM). A rare, immune-mediated myopathy characterized by proximal muscle weakness, muscle necrosis with markedly elevated creatine kinase levels, and the presence of autoantibodies to hydroxyl-methyl-glutaryl-coenzyme A reductase, in which muscle symptoms persist despite statin discontinuation.

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Adhyaru, B.B., Jacobson, T.A. Safety and efficacy of statin therapy. Nat Rev Cardiol 15, 757–769 (2018). https://doi.org/10.1038/s41569-018-0098-5

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