Dyslipidemias pp 403-421 | Cite as

Statins: Risk-Benefits and Role in Treating Dyslipidemias

  • Antonio M. GottoEmail author
  • Jennifer E. Moon
Part of the Contemporary Endocrinology book series (COE)


Statins are the mainstay of therapy for the management of dyslipidemia, and particularly elevations in low-density lipoprotein cholesterol (LDL-C). Currently available statins include atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin. The advent of statin therapy has contributed to a substantial decrease in cardiovascular mortality over the past several decades. Results from multiple clinical trials have shown conclusively that lowering LDL-C levels leads to clinical event reduction in primary and secondary prevention, for both men and women, and across various other patient subgroups. Extensive clinical experience indicates that statin therapy may be initiated and maintained over the long term with a high degree of safety, and adverse effects associated with statin use are outweighed by their proven benefits in clinical event reduction.


Statin Dyslipidemia Cardiovascular disease Prevention Low-density lipoprotein Lipid-lowering therapy 


  1. 1.
    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of The third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285:2486–97.CrossRefGoogle Scholar
  2. 2.
    Grundy SM, Cleeman JI, Merz CNB, Brewer HB Jr, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227–39.CrossRefPubMedGoogle Scholar
  3. 3.
    Product information. Lipitor (atorvastatin). New York: Pfizer; (February 2012.Google Scholar
  4. 4.
    Product information. Lescol, Lescol XL (fluvastatin). East Hanover: Novartis Pharmaceuticals Corporation; (February 2012).Google Scholar
  5. 5.
    Product information. Mevacor (lovastatin). Whitehouse Station: Merck; (February 2012).Google Scholar
  6. 6.
    Product information. Livalo (pitavastatin). Montgomery: Kowa; (June 2012).Google Scholar
  7. 7.
    Product information. Pravachol (pravastatin). Princeton: Bristol-Myers Squibb; (February 2012).Google Scholar
  8. 8.
    Product information. Crestor (rosuvastatin). Wilmington: AstraZeneca; (February 2012).Google Scholar
  9. 9.
    Product information. Zocor (simvastatin). Whitehouse Station: Merck; (June 2012).Google Scholar
  10. 10.
    Centers for Disease Control (Internet). Total and high-density lipoprotein cholesterol in adults: National Health and Nutrition Examination Survey, 2009–2010. 2012 Apr ([cited 2012 Sept 5];92).
  11. 11.
    National Heart, Lung, and Blood Institute (Internet). Morbidity & mortality: Chart Book on Cardiovascular, Lung, and Blood Diseases. [cited 2012 Sept 5] 2012.
  12. 12.
    Steinberg D. The cholesterol wars: the skeptics vs. the preponderance of the evidence. San Diego: Elsevier; 2007.Google Scholar
  13. 13.
    Endo A. The discovery and development of HMG-CoA reductase inhibitors. 1992. Atheroscler Suppl. 2004 ;5(3):67–80.CrossRefPubMedGoogle Scholar
  14. 14.
    Gotto AM, Pownall HJ. Manual of lipid disorders: reducing the risk for coronary heart disease. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2003.Google Scholar
  15. 15.
    McKenney JM, Ganz P, Wiggins BS, Saseen JS. Statins. In: Ballantyne CM, editor. Clinical lipidology: a companion to Braunwald’s Heart Disease. Philadelphia: Elsevier; 2009. p. 253–80.CrossRefGoogle Scholar
  16. 16.
    Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006;80(6):565–81.CrossRefPubMedGoogle Scholar
  17. 17.
    Prueksaritanont T, Tang C, Qui Y, Mu L, Subramanian R, Lin JH. Effects of fibrates on metabolism of statins in human hepatocytes. Drug Metabo Disp. 2002;30(11):1280–87.CrossRefGoogle Scholar
  18. 18.
    Sadowitz B, Maier KG, Gahtan V. Basic science review: statin therapy–Part I: The pleiotropic effects of statins in cardiovascular disease. Vasc Endovascular Surg. 2010; 44(4):241–51.CrossRefPubMedGoogle Scholar
  19. 19.
    Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.CrossRefPubMedGoogle Scholar
  20. 20.
    Ryu SK, Mallat Z, Benessiano J, Tedgui A, Olsson AG, Bao W, et al. Phospholipase A2 enzymes, high-dose atorvastatin, and prediction of ischemic events after acute coronary syndromes. Circulation. 2012; 125(6):757–66.CrossRefPubMedGoogle Scholar
  21. 21.
    Robinson JG, Smith B, Maheshwari N, Schrott H. Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis. J Am Coll Cardiol. 2005;46:1855–62.CrossRefPubMedGoogle Scholar
  22. 22.
    US Food and Drug Administration (Internet). FDA Drug Safety Communication: new restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. June 8, 2011. Accessed 26 Sept 2012.
  23. 23.
    Mangravite LM, Krauss RM. Pharmacogenomics of statin response. Curr Opin Lipidol. 2007;18(4):409–14.PubMedGoogle Scholar
  24. 24.
    Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003; 92(2):152–60.CrossRefPubMedGoogle Scholar
  25. 25.
    Nicholls SJ, Brandrup-Wognsen G, Palmer M, Barter PJ. Meta-analysis of comparative efficacy of increasing dose of atorvastatin versus rosuvastatin versus simvastatin on lowering levels of atherogenic lipids (from VOYAGER). Am J Cardiol. 2010;105(1):69–76.CrossRefPubMedGoogle Scholar
  26. 26.
    Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group, Armitage J, Bowman L, Wallendszus K, Bulbulia R, Rahimi K, et al. 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. 2010; 376:1658–69.CrossRefPubMedGoogle Scholar
  27. 27.
    Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81.CrossRefPubMedGoogle Scholar
  28. 28.
    Heart Protection Study Collaborative Group: MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22.CrossRefGoogle Scholar
  29. 29.
    Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335:1001–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. Results of AFCAPS/TexCAPS. JAMA. 1998;279:1615–22.CrossRefPubMedGoogle Scholar
  31. 31.
    Heart Protection Study Collaborative Group. Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20,536 high-risk individuals: a randomized controlled trial. Lancet. 2011; 378(9808):2013–20.CrossRefPubMedCentralGoogle Scholar
  32. 32.
    Strandberg TE, Pyörälä K, Cook TJ, Wilhelmsen L Faegerman O, Thorgeirsson G, et al. Mortality and incidence of cancer during 10-year follow-up of the scandinavian simvastatin survival study (4S). Lancet. 2004;364(9436):771–7.CrossRefPubMedGoogle Scholar
  33. 33.
    LIPID Study Group (Long-term Intervention with Pravastatin in Ischaemic Disease). Long-term effectiveness and safety of pravastatin in 9014 patients with coronary heart disease and average cholesterol concentrations: the LIPID trial follow-up. Lancet. 2002;359(9315):1379–87.CrossRefGoogle Scholar
  34. 34.
    Armitage J. The safety of statins in clinical practice. Lancet. 2007;370(9601):1781–90.CrossRefPubMedGoogle Scholar
  35. 35.
    US Food and Drug Administration (Internet). FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs [published 2012 Feb 28; cited 2012 Sept 4].
  36. 36.
    McKenney JM, Davidson MH, Jacobson TA, Guyton JR. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol. 2006;97(8A):89C–94C.CrossRefPubMedGoogle Scholar
  37. 37.
    Onofrei MD, Butler KL, Fuke DC, Miller HB. Safety of statin therapy in patients with preexisting liver disease. Pharmacotherapy. 2008;28(4):522–9.CrossRefPubMedGoogle Scholar
  38. 38.
    Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol. 2006;97(suppl):52C–60C.CrossRefPubMedGoogle Scholar
  39. 39.
    Jacobson TA. Toward “pain-free” statin prescribing: clinical algorithm for diagnosis and management of myalgia. Mayo Clin Proc. 2008;83(6):687–700.CrossRefPubMedGoogle Scholar
  40. 40.
    SEARCH Collaborative Group, Link E, Parish S, Armitage J, Bowman L, Heath S, et al. SLCO1B1 variants and statin-induced myopathy–a genomewide study. N Engl J Med. 2008;359(8):789–99.CrossRefPubMedGoogle Scholar
  41. 41.
    Voora D, Shah SH, Spasojevic I, Ali S, Reed CR, Salisbury BA, et al. The SLCO1B1*5 genetic variant is associated with statin-induced side effects. J Am Coll Cardiol. 2009;54(17):1609–16.CrossRefPubMedCentralPubMedGoogle Scholar
  42. 42.
    Harper CR, Jacobson TA. Evidence-based management of statin myopathy. Curr Atheroscler Rep. 2010;12:322–30.CrossRefPubMedGoogle Scholar
  43. 43.
    Sattar N, Preiss D, Murray HM, Welsh P, Buckley DM, de Craen AJ, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials. Lancet. 2010;375(9716):735–42.CrossRefPubMedGoogle Scholar
  44. 44.
    Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380(9841):565–71.CrossRefPubMedCentralPubMedGoogle Scholar
  45. 45.
    Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy. JAMA. 2011; 305:2556–64.CrossRefPubMedGoogle Scholar
  46. 46.
    Culver AL, Ockene IS, Balasubramanian R, Olendzki BC, Sepavich DM, Wactawski-Wende J, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Women’s Health Initiative. Arch Intern Med. 2012; 172(2):144–52.CrossRefPubMedGoogle Scholar
  47. 47.
    Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008; 371:117–25.CrossRefGoogle Scholar
  48. 48.
    Shitara Y, Sugiyama Y. Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: drug-drug interactions and interindividual differences in transporter and metabolic enzyme functions. Pharmacol Ther. 2006;112(1):71–105.CrossRefPubMedGoogle Scholar
  49. 49.
    ACCORD Study Group, Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010; 362(17):1563–74.CrossRefPubMedGoogle Scholar
  50. 50.
    Guyton JR, Bays HE. Safety considerations with niacin therapy. Am J Cardiol. 2007;99(6A):22C–31C.CrossRefPubMedGoogle Scholar
  51. 51.
    Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623–30.CrossRefPubMedGoogle Scholar
  52. 52.
    Kostis WJ, Cheng JQ, Dobrzynski JM, Cabrera J, Kostis JB. Meta-analysis of statin effects in women versus men. J Am Coll Cardiol. 2012;59:572–82.CrossRefPubMedGoogle Scholar
  53. 53.
    Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–504.CrossRefPubMedGoogle Scholar
  54. 54.
    LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425–35.CrossRefPubMedGoogle Scholar
  55. 55.
    Smith Jr SC, Benjamin EJ, Bonow RO, Braun LT, Creager MA, Franklin BA, et al. AHA/ACCF secondary prevention and risk reduction therapy for patients with coronary and other atherosclerotic vascular disease: 2011 update. Circulation. 2011;124:2458–73.CrossRefPubMedGoogle Scholar
  56. 56.
    Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, et al. 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. 2013. doi:pii: S0735-1097(13)06028–2. 10.1016/j.jacc.2013. 11.002 (epub ahead of print).Google Scholar
  57. 57.
    Brugts JJ, Yetgin T, Hoeks SE, Gotto AM, Shepherd J, Westendorp RG, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ. 2009;338:b2376.CrossRefPubMedCentralPubMedGoogle Scholar
  58. 58.
    Taylor F, Ward K, Moore TH, Burke M, Davey Smith G, Casas JP, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2011;19(1):CD004816.Google Scholar
  59. 59.
    Lazar LD, Pletcher MJ, Coxson PG, Bibbins-Domingo K, Goldman L. Cost-effectiveness of statin therapy for primary prevention in a low-cost statin era. Circulation. 2011;124:146–53.CrossRefPubMedGoogle Scholar
  60. 60.
    Cholesterol Treatment Trialists’ (CTT) 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. 2012; 380(9841): 581–90.CrossRefGoogle Scholar
  61. 61.
    Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301–7.CrossRefPubMedGoogle Scholar
  62. 62.
    Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) Study Group. N Engl J Med. 1998;339:1349–57.CrossRefGoogle Scholar
  63. 63.
    Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344(8934):1383–9.Google Scholar
  64. 64.
    Serruys PW, de Feyter P, Macaya C, Kokott N, Puel J, Vrolix M, et al. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;287(4):3215–22.CrossRefPubMedGoogle Scholar
  65. 65.
    Herd JA, Ballantyne CM, Farmer JA, Fergus JJ 3rd, Jones PH, West MS, et al. Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]). Am J Cardiol. 1997;80:278–86.CrossRefPubMedGoogle Scholar
  66. 66.
    Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, 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. 2003;361:1149–58.CrossRefPubMedGoogle Scholar
  67. 67.
    Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomized placebo-controlled trial. Lancet. 2004;364(9435):685–96.CrossRefPubMedGoogle Scholar
  68. 68.
    Sever PS, Poulter NR, Dahlöf B, Wedel H, Collins R, Beevers G, et al. Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial—lipid-lowering arm (ASCOT-LLA). Diabetes Care. 2005;28:1151–57.CrossRefPubMedGoogle Scholar
  69. 69.
    Shepherd J, Barter P, Carmena R, Deedwania P, Fruchart JC, Haffner S, et al. Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study. Diabetes Care. 2006;29(6):1220–6.CrossRefPubMedGoogle Scholar
  70. 70.
    Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549–59.CrossRefPubMedGoogle Scholar
  71. 71.
    Nissen SE, Tuzcu EM, Schoenhagen P, Brown BG, Ganz P, Vogel RA, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004;291:1071–1080.CrossRefPubMedGoogle Scholar
  72. 72.
    Nissen SE, Nicholls SJ, Sipahi I, Libby P, Raichlen JS, Ballantyne CM, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295:1556–1565.CrossRefPubMedGoogle Scholar
  73. 73.
    Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O’Leary DH, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: the METEOR Trial. JAMA. 2007;297:1344–1353.CrossRefPubMedGoogle Scholar
  74. 74.
    Budinski D, Arneson V, Hounslow N, Gratsiansky N. Pitavastatin compared with atorvastatin in primary hypercholesterolemia or combined dyslipidemia. Clin Lipidol. 2009; 4(3):291–302.CrossRefGoogle Scholar
  75. 75.
    Ose L, Budinski D, Hounslow N, Arneson V. Comparison of pitavastatin with simvastatin in primary hypercholesterolemia or combined dyslipidemia. Curr Med Res Opin. 2009;25(10): 2755–64.PubMedGoogle Scholar
  76. 76.
    Hiro T, Kimura T, Morimoto T, Miyauchi K, Nakagawa Y, Yamagishi M, et al. Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute coronary syndrome. J Am Coll Cardiol. 2009; 54(4):293–302.CrossRefPubMedGoogle Scholar
  77. 77.
    Yokote K, Shimano H, Urashima M, Teramoto T. Efficacy and safety of pitavastatin in Japanese patients with hypercholesterolemia: LIVES study and subanalysis. Expert Rev Cardiovasc Ther. 2011;9(5):555–62.CrossRefPubMedGoogle Scholar
  78. 78.
    National Heart, Lung, and Blood Institute. Expert Panel on Integrated Guidelines for cardiovascular Health and risk reduction in children and adolescents. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128(Suppl 5): S213–56.Google Scholar
  79. 79.
    Goldberg AC, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG, et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011;5:133–40.CrossRefPubMedGoogle Scholar
  80. 80.
    Godfrey LM, Erramouspe J, Cleveland KW. Teratogenic risk of statins in pregnancy. Ann Pharmacother. 2012;46(10):1419–24.CrossRefPubMedGoogle Scholar

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© Humana Press 2015

Authors and Affiliations

  1. 1.Weill Cornell Medical CollegeNew YorkUSA

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