Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Statins: Actions, side effects, and administration

INTRODUCTION

Lipid altering agents encompass several classes of drugs that include HMG CoA reductase (hydroxymethylglutaryl CoA reductase) inhibitors or statins, fibric acid derivatives, bile acid sequestrants, cholesterol absorption inhibitors, and nicotinic acid. These drugs differ with respect to mechanism of action and to the degree and type of lipid lowering. Thus, the indications for a particular drug are influenced by the underlying lipid abnormality. Conventional dosing regimens and common adverse reactions are described in a table (table 1) and the range of expected changes in the lipid profile are listed in a separate table (table 2).

Lipid lowering, at least with statins, is beneficial in patients with dyslipidemias for both primary and secondary prevention of coronary heart disease. (See "Clinical trials of cholesterol lowering for primary prevention of coronary heart disease" and "Clinical trials of cholesterol lowering in patients with cardiovascular disease or diabetes".)

The mechanisms of benefit seen with lipid lowering are incompletely understood. Regression of atherosclerosis occurs in only a minority of patients; furthermore, clinical benefits of lipid lowering are seen in as little as six months, before significant regression could occur. Thus, other factors must contribute; these include plaque stabilization, reversal of endothelial dysfunction, and decreased thrombogenicity. (See "Mechanisms of benefit of lipid-lowering drugs in patients with coronary heart disease".)

The characteristics and efficacy of the statins will be reviewed here (table 3). Possible noncardiovascular benefits of statins are discussed separately. (See "Statins: Possible noncardiovascular benefits".) The efficacy of fibrates, lipid lowering drugs other than statins and fibrates, and diet and dietary supplements are also discussed separately. (See "Lipid lowering with fibric acid derivatives" and "Lipid lowering with drugs other than statins and fibrates" and "Lipid lowering with diet or dietary supplements".)

Therapeutic decision making in patients with elevated lipid levels, including indications for and dosing of statins, is discussed in detail separately:

                              

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Mar 2014. | This topic last updated: Feb 24, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Istvan ES, Deisenhofer J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science 2001; 292:1160.
  2. Ness GC, Zhao Z, Lopez D. Inhibitors of cholesterol biosynthesis increase hepatic low-density lipoprotein receptor protein degradation. Arch Biochem Biophys 1996; 325:242.
  3. Conde K, Vergara-Jimenez M, Krause BR, et al. Hypocholesterolemic actions of atorvastatin are associated with alterations on hepatic cholesterol metabolism and lipoprotein composition in the guinea pig. J Lipid Res 1996; 37:2372.
  4. Arad Y, Ramakrishnan R, Ginsberg HN. Lovastatin therapy reduces low density lipoprotein apoB levels in subjects with combined hyperlipidemia by reducing the production of apoB-containing lipoproteins: implications for the pathophysiology of apoB production. J Lipid Res 1990; 31:567.
  5. Ness GC, Chambers CM, Lopez D. Atorvastatin action involves diminished recovery of hepatic HMG-CoA reductase activity. J Lipid Res 1998; 39:75.
  6. Larsen ML, Illingworth DR. Drug treatment of dyslipoproteinemia. Med Clin North Am 1994; 78:225.
  7. Levy RI, Troendle AJ, Fattu JM. A quarter century of drug treatment of dyslipoproteinemia, with a focus on the new HMG-CoA reductase inhibitor fluvastatin. Circulation 1993; 87:III45.
  8. Illingworth DR, Stein EA, Mitchel YB, et al. Comparative effects of lovastatin and niacin in primary hypercholesterolemia. A prospective trial. Arch Intern Med 1994; 154:1586.
  9. Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol 1998; 81:582.
  10. Rosenson RS. Rosuvastatin: a new inhibitor of HMG-coA reductase for the treatment of dyslipidemia. Expert Rev Cardiovasc Ther 2003; 1:495.
  11. Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol 2003; 92:152.
  12. Brown AS, Bakker-Arkema RG, Yellen L, et al. Treating patients with documented atherosclerosis to National Cholesterol Education Program-recommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin. J Am Coll Cardiol 1998; 32:665.
  13. Eidelman RS, Lamas GA, Hennekens CH. The new National Cholesterol Education Program guidelines: clinical challenges for more widespread therapy of lipids to treat and prevent coronary heart disease. Arch Intern Med 2002; 162:2033.
  14. www.fda.gov/Drugs/DrugSafety/ucm256581.htm (Accessed on March 15, 2013).
  15. Sprecher DL, Abrams J, Allen JW, et al. Low-dose combined therapy with fluvastatin and cholestyramine in hyperlipidemic patients. Ann Intern Med 1994; 120:537.
  16. Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med 1990; 323:1289.
  17. Pan HY, DeVault AR, Swites BJ, et al. Pharmacokinetics and pharmacodynamics of pravastatin alone and with cholestyramine in hypercholesterolemia. Clin Pharmacol Ther 1990; 48:201.
  18. Rosenson RS, Otvos JD, Hsia J. Effects of rosuvastatin and atorvastatin on LDL and HDL particle concentrations in patients with metabolic syndrome: a randomized, double-blind, controlled study. Diabetes Care 2009; 32:1087.
  19. März W, Scharnagl H, Abletshauser C, et al. Fluvastatin lowers atherogenic dense low-density lipoproteins in postmenopausal women with the atherogenic lipoprotein phenotype. Circulation 2001; 103:1942.
  20. Otvos JD, Shalaurova I, Freedman DS, Rosenson RS. Effects of pravastatin treatment on lipoprotein subclass profiles and particle size in the PLAC-I trial. Atherosclerosis 2002; 160:41.
  21. Albert MA, Danielson E, Rifai N, et al. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA 2001; 286:64.
  22. Kastelein JJ, Isaacsohn JL, Ose L, et al. Comparison of effects of simvastatin versus atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I levels. Am J Cardiol 2000; 86:221.
  23. Bakker-Arkema RG, Davidson MH, Goldstein RJ, et al. Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia. JAMA 1996; 275:128.
  24. Davidson M, McKenney J, Stein E, et al. Comparison of one-year efficacy and safety of atorvastatin versus lovastatin in primary hypercholesterolemia. Atorvastatin Study Group I. Am J Cardiol 1997; 79:1475.
  25. Dart A, Jerums G, Nicholson G, et al. A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemia. Am J Cardiol 1997; 80:39.
  26. Mulder AB, van Lijf HJ, Bon MA, et al. Association of polymorphism in the cytochrome CYP2D6 and the efficacy and tolerability of simvastatin. Clin Pharmacol Ther 2001; 70:546.
  27. Chasman DI, Posada D, Subrahmanyan L, et al. Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA 2004; 291:2821.
  28. Liao JK. Safety and efficacy of statins in Asians. Am J Cardiol 2007; 99:410.
  29. www.astrazeneca-us.com/pi/crestor.pdf (Accessed on February 08, 2007).
  30. Rosenson RS. Current overview of statin-induced myopathy. Am J Med 2004; 116:408.
  31. Brewer HB Jr. Benefit-risk assessment of Rosuvastatin 10 to 40 milligrams. Am J Cardiol 2003; 92:23K.
  32. Bruckert E, Hayem G, Dejager S, et al. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study. Cardiovasc Drugs Ther 2005; 19:403.
  33. Kashani A, Phillips CO, Foody JM, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation 2006; 114:2788.
  34. Armitage J. The safety of statins in clinical practice. Lancet 2007; 370:1781.
  35. Zhang H, Plutzky J, Skentzos S, et al. Discontinuation of statins in routine care settings: a cohort study. Ann Intern Med 2013; 158:526.
  36. Björnsson E, Jacobsen EI, Kalaitzakis E. Hepatotoxicity associated with statins: reports of idiosyncratic liver injury post-marketing. J Hepatol 2012; 56:374.
  37. Cohen DE, Anania FA, Chalasani N, National Lipid Association Statin Safety Task Force Liver Expert Panel. An assessment of statin safety by hepatologists. Am J Cardiol 2006; 97:77C.
  38. Downs JR, Clearfield M, Weis S, 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 1998; 279:1615.
  39. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344:1383.
  40. 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.
  41. Pfeffer MA, Keech A, Sacks FM, et al. Safety and tolerability of pravastatin in long-term clinical trials: prospective Pravastatin Pooling (PPP) Project. Circulation 2002; 105:2341.
  42. Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ 2010; 340:c2197.
  43. Smith CC, Bernstein LI, Davis RB, et al. Screening for statin-related toxicity: the yield of transaminase and creatine kinase measurements in a primary care setting. Arch Intern Med 2003; 163:688.
  44. Charles EC, Olson KL, Sandhoff BG, et al. Evaluation of cases of severe statin-related transaminitis within a large health maintenance organization. Am J Med 2005; 118:618.
  45. http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm (Accessed on February 28, 2012).
  46. Weismantel D, Danis P. Clinical inquiries. What laboratory monitoring is appropriate to detect adverse drug reactions in patients on cholesterol-lowering agents? J Fam Pract 2001; 50:927.
  47. Gotto AM Jr. Safety and statin therapy: reconsidering the risks and benefits. Arch Intern Med 2003; 163:657.
  48. Ballantyne CM, Corsini A, Davidson MH, et al. Risk for myopathy with statin therapy in high-risk patients. Arch Intern Med 2003; 163:553.
  49. Thompson PD, Clarkson PM, Rosenson RS, National Lipid Association Statin Safety Task Force Muscle Safety Expert Panel. An assessment of statin safety by muscle experts. Am J Cardiol 2006; 97:69C.
  50. Bar SL, Holmes DT, Frohlich J. Asymptomatic hypothyroidism and statin-induced myopathy. Can Fam Physician 2007; 53:428.
  51. Lando HM, Burman KD. Two cases of statin-induced myopathy caused by induced hypothyroidism. Endocr Pract 2008; 14:726.
  52. Vidt DG, Cressman MD, Harris S, et al. Rosuvastatin-induced arrest in progression of renal disease. Cardiology 2004; 102:52.
  53. Sidaway JE, Davidson RG, McTaggart F, et al. Inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase reduce receptor-mediated endocytosis in opossum kidney cells. J Am Soc Nephrol 2004; 15:2258.
  54. Alsheikh-Ali AA, Ambrose MS, Kuvin JT, Karas RH. The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis. Circulation 2005; 111:3051.
  55. Grundy SM. The issue of statin safety: where do we stand? Circulation 2005; 111:3016.
  56. www.fda.gov/cder/drug/infopage/rosuvastatin/crestor_CP.pdf (Accessed on June 10, 2005).
  57. McAfee AT, Ming EE, Seeger JD, et al. The comparative safety of rosuvastatin: a retrospective matched cohort study in over 48,000 initiators of statin therapy. Pharmacoepidemiol Drug Saf 2006; 15:444.
  58. Guthrie RM, Martin DR. The safety of rosuvastatin: effects on renal and hepatic function. Expert Opin Drug Saf 2007; 6:573.
  59. García-Rodríguez LA, Massó-González EL, Wallander MA, Johansson S. The safety of rosuvastatin in comparison with other statins in over 100,000 statin users in UK primary care. Pharmacoepidemiol Drug Saf 2008; 17:943.
  60. García-Rodríguez LA, González-Pérez A, Stang MR, et al. The safety of rosuvastatin in comparison with other statins in over 25,000 statin users in the Saskatchewan Health Databases. Pharmacoepidemiol Drug Saf 2008; 17:953.
  61. Yang CC, Jick SS, Jick H. Lipid-lowering drugs and the risk of depression and suicidal behavior. Arch Intern Med 2003; 163:1926.
  62. Golomb BA, Kane T, Dimsdale JE. Severe irritability associated with statin cholesterol-lowering drugs. QJM 2004; 97:229.
  63. Redelmeier DA, Thiruchelvam D, Daneman N. Delirium after elective surgery among elderly patients taking statins. CMAJ 2008; 179:645.
  64. Marcantonio ER. Statins and postoperative delirium. CMAJ 2008; 179:627.
  65. CGS News www.cbsnews.com/stories/2004/05/24/eveningnews/main619351.shtml (Accessed on March 07, 2005).
  66. Graveline D. Lipitor: Thief of memory: Statin Drugs and the Misguided War on Cholesterol, Infinity Publishing, Haverford, PA 2004.
  67. Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy 2003; 23:871.
  68. Muldoon MF, Barger SD, Ryan CM, et al. Effects of lovastatin on cognitive function and psychological well-being. Am J Med 2000; 108:538.
  69. Muldoon MF, Ryan CM, Sereika SM, et al. Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults. Am J Med 2004; 117:823.
  70. Richardson K, Schoen M, French B, et al. Statins and cognitive function: a systematic review. Ann Intern Med 2013; 159:688.
  71. Rojas-Fernandez CH, Cameron JC. Is statin-associated cognitive impairment clinically relevant? A narrative review and clinical recommendations. Ann Pharmacother 2012; 46:549.
  72. Newman TB, Hulley SB. Carcinogenicity of lipid-lowering drugs. JAMA 1996; 275:55.
  73. Baigent C, Keech A, Kearney PM, 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 2005; 366:1267.
  74. Dale KM, Coleman CI, Henyan NN, et al. Statins and cancer risk: a meta-analysis. JAMA 2006; 295:74.
  75. Browning DR, Martin RM. Statins and risk of cancer: a systematic review and metaanalysis. Int J Cancer 2007; 120:833.
  76. Strandberg TE, Pyörälä K, Cook TJ, et al. Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S). Lancet 2004; 364:771.
  77. Ford I, Murray H, Packard CJ, et al. Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med 2007; 357:1477.
  78. Heart Protection Study Collaborative Group, Bulbulia R, Bowman L, et al. Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20,536 high-risk individuals: a randomised controlled trial. Lancet 2011; 378:2013.
  79. Yu Y, Ohmori K, Chen Y, et al. Effects of pravastatin on progression of glucose intolerance and cardiovascular remodeling in a type II diabetes model. J Am Coll Cardiol 2004; 44:904.
  80. Wong V, Stavar L, Szeto L, et al. Atorvastatin induces insulin sensitization in Zucker lean and fatty rats. Atherosclerosis 2006; 184:348.
  81. Chen Y, Ohmori K, Mizukawa M, et al. Differential impact of atorvastatin vs pravastatin on progressive insulin resistance and left ventricular diastolic dysfunction in a rat model of type II diabetes. Circ J 2007; 71:144.
  82. Mita T, Watada H, Nakayama S, et al. Preferable effect of pravastatin compared to atorvastatin on beta cell function in Japanese early-state type 2 diabetes with hypercholesterolemia. Endocr J 2007; 54:441.
  83. Yamakawa T, Takano T, Tanaka S, et al. Influence of pitavastatin on glucose tolerance in patients with type 2 diabetes mellitus. J Atheroscler Thromb 2008; 15:269.
  84. Sathyapalan T, Kilpatrick ES, Coady AM, Atkin SL. The effect of atorvastatin in patients with polycystic ovary syndrome: a randomized double-blind placebo-controlled study. J Clin Endocrinol Metab 2009; 94:103.
  85. Freeman DJ, Norrie J, Sattar N, et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 2001; 103:357.
  86. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359:2195.
  87. Shepherd J. Glasgow Royal Infirmary, 2008, personal communication.
  88. Coleman CI, Reinhart K, Kluger J, White CM. The effect of statins on the development of new-onset type 2 diabetes: a meta-analysis of randomized controlled trials. Curr Med Res Opin 2008; 24:1359.
  89. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010; 375:735.
  90. Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 2011; 305:2556.
  91. Carter AA, Gomes T, Camacho X, et al. Risk of incident diabetes among patients treated with statins: population based study. BMJ 2013; 346:f2610.
  92. Ridker PM, Pradhan A, MacFadyen JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet 2012; 380:565.
  93. Wang KL, Liu CJ, Chao TF, et al. Statins, risk of diabetes, and implications on outcomes in the general population. J Am Coll Cardiol 2012.
  94. Gerson RJ, MacDonald JS, Alberts AW, et al. On the etiology of subcapsular lenticular opacities produced in dogs receiving HMG-CoA reductase inhibitors. Exp Eye Res 1990; 50:65.
  95. Schlienger RG, Haefeli WE, Jick H, Meier CR. Risk of cataract in patients treated with statins. Arch Intern Med 2001; 161:2021.
  96. Smeeth L, Hubbard R, Fletcher AE. Cataract and the use of statins: a case-control study. QJM 2003; 96:337.
  97. Klein BE, Klein R, Lee KE, Grady LM. Statin use and incident nuclear cataract. JAMA 2006; 295:2752.
  98. Harris ML, Bron AJ, Brown NA, et al. Absence of effect of simvastatin on the progression of lens opacities in a randomised placebo controlled study. Oxford Cholesterol Study Group. Br J Ophthalmol 1995; 79:996.
  99. Leuschen J, Mortensen EM, Frei CR, et al. Association of statin use with cataracts: a propensity score-matched analysis. JAMA Ophthalmol 2013; 131:1427.
  100. Gaist D, Jeppesen U, Andersen M, et al. Statins and risk of polyneuropathy: a case-control study. Neurology 2002; 58:1333.
  101. Anderson JL, Muhlestein JB, Bair TL, et al. Do statins increase the risk of idiopathic polyneuropathy? Am J Cardiol 2005; 95:1097.
  102. Dobs AS, Schrott H, Davidson MH, et al. Effects of high-dose simvastatin on adrenal and gonadal steroidogenesis in men with hypercholesterolemia. Metabolism 2000; 49:1234.
  103. Davidson MH, Stein EA, Dujovne CA, et al. The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day. Am J Cardiol 1997; 79:38.
  104. Azzarito C, Boiardi L, Vergoni W, et al. Testicular function in hypercholesterolemic male patients during prolonged simvastatin treatment. Horm Metab Res 1996; 28:193.
  105. Santini SA, Carrozza C, Lulli P, et al. Atorvastatin treatment does not affect gonadal and adrenal hormones in type 2 diabetes patients with mild to moderate hypercholesterolemia. J Atheroscler Thromb 2003; 10:160.
  106. Hosokawa A, Bar-Oz B, Ito S. Use of lipid-lowering agents (statins) during pregnancy. Can Fam Physician 2003; 49:747.
  107. Edison RJ, Muenke M. Central nervous system and limb anomalies in case reports of first-trimester statin exposure. N Engl J Med 2004; 350:1579.
  108. Kazmin A, Garcia-Bournissen F, Koren G. Risks of statin use during pregnancy: a systematic review. J Obstet Gynaecol Can 2007; 29:906.
  109. Taguchi N, Rubin ET, Hosokawa A, et al. Prenatal exposure to HMG-CoA reductase inhibitors: effects on fetal and neonatal outcomes. Reprod Toxicol 2008; 26:175.
  110. Costantine MM, Cleary K, Eunice Kennedy Shriver National Institute of Child Health and Human Development Obstetric--Fetal Pharmacology Research Units Network. Pravastatin for the prevention of preeclampsia in high-risk pregnant women. Obstet Gynecol 2013; 121:349.
  111. Miettinen TA. Diurnal variation of cholesterol precursors squalene and methyl sterols in human plasma lipoproteins. J Lipid Res 1982; 23:466.
  112. Saito Y, Yoshida S, Nakaya N, et al. Comparison between morning and evening doses of simvastatin in hyperlipidemic subjects. A double-blind comparative study. Arterioscler Thromb 1991; 11:816.
  113. Wallace A, Chinn D, Rubin G. Taking simvastatin in the morning compared with in the evening: randomised controlled trial. BMJ 2003; 327:788.
  114. Cilla DD Jr, Gibson DM, Whitfield LR, Sedman AJ. Pharmacodynamic effects and pharmacokinetics of atorvastatin after administration to normocholesterolemic subjects in the morning and evening. J Clin Pharmacol 1996; 36:604.
  115. Rindone JP, Hiller D, Arriola G. A comparison of fluvastatin 40 mg every other day versus 20 mg every day in patients with hypercholesterolemia. Pharmacotherapy 1998; 18:836.
  116. Matalka MS, Ravnan MC, Deedwania PC. Is alternate daily dose of atorvastatin effective in treating patients with hyperlipidemia? The Alternate Day Versus Daily Dosing of Atorvastatin Study (ADDAS). Am Heart J 2002; 144:674.
  117. Jafari M, Ebrahimi R, Ahmadi-Kashani M, et al. Efficacy of alternate-day dosing versus daily dosing of atorvastatin. J Cardiovasc Pharmacol Ther 2003; 8:123.
  118. Ferrer-García JC, Pérez-Silvestre J, Martínez-Mir I, Herrera-Ballester A. Alternate-day dosing of atorvastatin: effects in treating type 2 diabetic patients with dyslipidaemia. Acta Diabetol 2006; 43:75.
  119. Wongwiwatthananukit S, Sansanayudh N, Dhummauppakorn R, Kitiyadisai C. Efficacy and safety of rosuvastatin every other day compared with once daily in patients with hypercholesterolemia. Ann Pharmacother 2006; 40:1917.
  120. 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; 42:341.
  121. Kayikçioğlu M, Ozerkan F, Soydan I. Effectiveness and safety of alternate-day simvastatin and fenofibrate on mixed hyperlipidemia. Am J Cardiol 1999; 83:1135.
  122. Ruisinger JF, Backes JM, Gibson CA, Moriarty PM. Once-a-week rosuvastatin (2.5 to 20 mg) in patients with a previous statin intolerance. Am J Cardiol 2009; 103:393.
  123. Drugs for lipids. Treat Guidel Med Lett 2008; 6:9.
  124. www.fda.gov/Safety/MedWatch/SafetyInformation/ucm200635.htm (Accessed on February 19, 2010).
  125. Chong PH, Seeger JD, Franklin C. Clinically relevant differences between the statins: implications for therapeutic selection. Am J Med 2001; 111:390.
  126. Kasiske BL, Wanner C, O'Neill WC, National Lipid Association Statin Safety Task Force Kidney Expert Panel. An assessment of statin safety by nephrologists. Am J Cardiol 2006; 97:82C.
  127. Tonelli M, Moyé L, Sacks FM, et al. Pravastatin for secondary prevention of cardiovascular events in persons with mild chronic renal insufficiency. Ann Intern Med 2003; 138:98.
  128. Chalasani N, Aljadhey H, Kesterson J, et al. Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology 2004; 126:1287.
  129. Khorashadi S, Hasson NK, Cheung RC. Incidence of statin hepatotoxicity in patients with hepatitis C. Clin Gastroenterol Hepatol 2006; 4:902.
  130. Lewis JH, Mortensen ME, Zweig S, et al. Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: Results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Hepatology 2007; 46:1453.
  131. Athyros VG, Tziomalos K, Gossios TD, 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 2010; 376:1916.
  132. Stojakovic T, Putz-Bankuti C, Fauler G, et al. Atorvastatin in patients with primary biliary cirrhosis and incomplete biochemical response to ursodeoxycholic acid. Hepatology 2007; 46:776.
  133. Sorokin A, Brown JL, Thompson PD. Primary biliary cirrhosis, hyperlipidemia, and atherosclerotic risk: a systematic review. Atherosclerosis 2007; 194:293.
  134. Abu Rajab M, Kaplan MM. Statins in primary biliary cirrhosis: are they safe? Dig Dis Sci 2010; 55:2086.