Non-cardiovascular effects associated with statins

BMJ (Online)

Volumn 349, Issue , 2014, Pages

  Desai, Chintan S ^a   Martin, Seth S ^a   Blumenthal, Roger S ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; AMINOTRANSFERASE; ATORVASTATIN; C REACTIVE PROTEIN; CERIVASTATIN; CREATINE KINASE; CREATININE; D DIMER; FLUINDOSTATIN; GLUCOSE; GLYCOSYLATED HEMOGLOBIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MEVINOLIN; PLACEBO; PRAVASTATIN; ROSUVASTATIN; SIMVASTATIN; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B1;

ACUTE CORONARY SYNDROME; ACUTE KIDNEY FAILURE; ALLELE; AMINOTRANSFERASE BLOOD LEVEL; ANGIOCARDIOGRAPHY; ATTENTION; BODY MASS; BREAST CANCER; CANCER MORTALITY; CATARACT; CHRONIC OBSTRUCTIVE LUNG DISEASE; COGNITION; COGNITIVE DEFECT; CONTRAST INDUCED NEPHROPATHY; CORONARY ARTERY ATHEROSCLEROSIS; DEMENTIA; DIABETES MELLITUS; DIET RESTRICTION; DIGESTIVE SYSTEM CANCER; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MEGADOSE; DRUG POTENCY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ERECTILE DYSFUNCTION; EXERCISE TEST; FATIGUE; FATTY LIVER; GENETIC ASSOCIATION; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GLUCOSE BLOOD LEVEL; HEART FAILURE; HEMODIALYSIS; HIGH RISK PATIENT; HUMAN; KIDNEY DISEASE; KIDNEY FAILURE; LIVER DISEASE; LIVER FAILURE; LIVER METABOLISM; LIVER TOXICITY; LOW DRUG DOSE; MALIGNANT NEOPLASTIC DISEASE; MENTAL CONCENTRATION; META ANALYSIS (TOPIC); METABOLIC SYNDROME X; MORBIDITY; MORTALITY; MUSCLE FUNCTION; MUSCLE STRENGTH; MUSCULOSKELETAL DISEASE; MYALGIA; MYOPATHY; MYOSITIS; NEUROPSYCHOLOGICAL TEST; OXIDATIVE STRESS; PANCREATITIS; PATHOPHYSIOLOGY; PLEIOTROPY; PRACTICE GUIDELINE; PRIMARY PREVENTION; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RENAL REPLACEMENT THERAPY; REVIEW; RHABDOMYOLYSIS; RISK FACTOR; SECONDARY PREVENTION; SIDE EFFECT; SINGLE NUCLEOTIDE POLYMORPHISM; SLCO1B1 GENE; SYMPTOMATOLOGY; SYSTEMATIC REVIEW; TREATMENT DURATION; VENOUS THROMBOEMBOLISM;

ACUTE KIDNEY INJURY; CATARACT; CLINICAL TRIALS AS TOPIC; COGNITION; CONTRAST MEDIA; DEMENTIA; DIABETES MELLITUS; DRUG-INDUCED LIVER INJURY; ERECTILE DYSFUNCTION; FATIGUE; GENETIC PREDISPOSITION TO DISEASE; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERCHOLESTEROLEMIA; KIDNEY DISEASES; LIVER; MALE; META-ANALYSIS AS TOPIC; MUSCULAR DISEASES; NEOPLASMS; ORGANIC ANION TRANSPORTERS; PANCREATITIS; POLYMORPHISM, SINGLE NUCLEOTIDE; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; RESEARCH DESIGN; RISK FACTORS; TRANSAMINASES; VENOUS THROMBOEMBOLISM;

EID: 84904497873     PISSN: None     EISSN: 17561833     Source Type: Journal    
DOI: 10.1136/bmj.g3743     Document Type: Review

References (96)

1. Blaha MJ, Martin SS. How do statins work? Changing paradigms with implications for statin allocation. J Am Coll Cardiol 2013;62:2392-4.
2. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, 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.
3. Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, et al. 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;380:581-90.
4. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a metaanalysis of data from 170 000 participants in 26 randomised trials. Lancet 2010;376:1670-81.
5. Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 2011;365:2078-87.
6. Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, et al. ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769-818.
7. Stone NJ, Robinson J, Lichtenstein AH, Bairey Merz CN, Lloyd-Jones DM, Blum CB, 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 2013; pii:S0735-1097(13)06028-2.
8. Vaughan CJ, Gotto AM Jr, Basson CT. The evolving role of statins in the management of atherosclerosis. J Am Coll Cardiol 2000;35:1-10. (Pubitemid 30061252)
9. Fassett RG, Robertson IK, Ball MJ, Geraghty DP, Coombes JS. Effects of atorvastatin on biomarkers of inflammation in chronic kidney disease. Clin Nephrol 2014;81:75-85.
10. Pasternak RC, Smith SC Jr, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. J Am Coll Cardiol 2002;40:567-72. (Pubitemid 34833176)
11. Armitage J. The safety of statins in clinical practice. Lancet 2007;370:1781-90. (Pubitemid 350137473)
12. De Lemos JA, Blazing MA, Wiviott SD, Lewis EF, Fox KA, White HD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004;292:1307-16. (Pubitemid 39223221)
13. Armitage J, Bowman L, Wallendszus K, Bulbulia R, Rahimi K, Haynes R, 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.
14. Kashani A, Phillips CO, Foody JM, Wang Y, Mangalmurti S, Ko DT, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation 2006;114:2788-97. (Pubitemid 46018281)
15. Finegold JA, Manisty CH, Goldacre B, Barron AJ, Francis DP. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice. Eur J Prev Cardiol 2014; published online 12 Mar.
16. US Food and Drug Administration. For consumers. FDA: limit use of 80 mg simvastatin. 2013. www.fda.gov/forconsumers/consumerupdates/ucm257884.htm.
17. Buettner C, Davis RB, Leveille SG, Mittleman MA, Mukamal KJ. Prevalence of musculoskeletal pain and statin use. J Gen Intern Med 2008;23:1182-6.
18. 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 2005;19:403-14. (Pubitemid 43228152)
19. 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.
20. Armitage J, Bowman L, Collins R, Parish S, Tobert J. Effects of simvastatin 40 mg daily on muscle and liver adverse effects in a 5-year randomized placebocontrolled trial in 20 536 high-risk people. BMC Clin Pharmacol 2009;9:6.
21. Mansi I, Mortensen E. The controversy of a wider statin utilization: why? Expert Opin Drug Saf 2013;12:327-37.
22. 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. (Pubitemid 40471450)
23. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-9.
24. 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. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998;279:1615-22. (Pubitemid 28248586)
25. 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.
26. Fellstrom BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009;360:1395-407.
27. Parker BA, Capizzi JA, Grimaldi AS, Clarkson PM, Cole SM, Keadle J, et al. Effect of statins on skeletal muscle function. Circulation 2013;127:96-103.
28. Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, et al. SLCO1B1 variants and statin-induced myopathy-a genomewide study. N Engl J Med 2008;359:789-99.
29. 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;54:1609-16.
30. Donnelly LA, Doney AS, Tavendale R, Lang CC, Pearson ER, Colhoun HM, et al. Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: a go-DARTS study. Clin Pharmacol Ther 2011;89:210-6.
31. Santos PC, Gagliardi AC, Miname MH, Chacra AP, Santos RD, Krieger JE, et al. SLCO1B1 haplotypes are not associated with atorvastatin-induced myalgia in Brazilian patients with familial hypercholesterolemia. Eur J Clin Pharmacol 2012;68:273-9.
32. Mampuya WM, Frid D, Rocco M, Huang J, Brennan DM, Hazen SL, et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience. Am Heart J 2013;166:597-603.
33. Zhang H, Plutzky J, Skentzos S, Morrison F, Mar P, Shubina M, et al. Discontinuation of statins in routine care settings: a cohort study. Ann Intern Med 2013;158:526-34.
34. Nakata M, Nagasaka S, Kusaka I, Matsuoka H, Ishibashi S, Yada T. Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control. Diabetologia 2006;49:1881-92. (Pubitemid 44025043)
35. Chamberlain LH. Inhibition of isoprenoid biosynthesis causes insulin resistance in 3T3-L1 adipocytes. FEBS Lett 2001;507:357-61. (Pubitemid 33030265)
36. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Park JB, et al. Differential metabolic effects of pravastatin and simvastatin in hypercholesterolemic patients. Atherosclerosis 2009;204:483-90.
37. Navarese EP, Szczesniak A, Kolodziejczak M, Gorny B, Kubica J, Suryapranata H. Statins and risk of new-onset diabetes mellitus: is there a rationale for individualized statin therapy? Am J Cardiovasc Drugs 2014;14:79-87.
38. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010;375:735-42.
39. 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: a meta-analysis. JAMA 2011;305:2556-64.
40. Pedersen TR, Faergeman O, Kastelein JJ, Olsson AG, Tikkanen MJ, Holme I, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 2005;294:2437-45. (Pubitemid 41627921)
41. 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;380:565-71.
42. Tolman KG. Defining patient risks from expanded preventive therapies. Am J Cardiol 2000;85:15E-9E.
43. De Denus S, Spinler SA, Miller K, Peterson AM. Statins and liver toxicity: a meta-analysis. Pharmacotherapy 2004;24:584-91. (Pubitemid 38585952)
44. Alsheikh-Ali AA, Maddukuri PV, Han H, Karas RH. Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: insights from large randomized statin trials. J Am Coll Cardiol 2007;50:409-18. (Pubitemid 47096680)
45. Cohen DE, Anania FA, Chalasani N. An assessment of statin safety by hepatologists. Am J Cardiol 2006;97:77C-81C.
46. Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med 2006;354:731-9. (Pubitemid 43247143)
47. Bader T. The myth of statin-induced hepatotoxicity. Am J Gastroenterol 2010;105:978-80.
48. Golomb BA, Evans MA. Statin adverse effects : a review of the literature and evidence for a mitochondrial mechanism. Am J Cardiovasc Drugs 2008;8:373-418.
49. Laties AM, Shear CL, Lippa EA, Gould AL, Taylor HR, Hurley DP, et al. Expanded clinical evaluation of lovastatin (EXCEL) study results. II. Assessment of the human lens after 48 weeks of treatment with lovastatin. Am J Cardiol 1991;67:447-53.
50. Harris ML, Bron AJ, Brown NA, Keech AC, Wallendszus KR, Armitage JM, 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;79:996-1002.
51. Klein BE, Klein R, Lee KE, Grady LM. Statin use and incident nuclear cataract. JAMA 2006;295:2752-8.
52. 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.
53. Rosenberg M. Do you really need that statin? This expert says no. HuffPost Healthy Living: The Blog 2012. www.huffingtonpost.com/martharosenberg/ statins-b-1818370.html.
54. Parker-Pope T. Well: a heart helper may come at a price for the brain. New York Times 2012. http://query.nytimes.com/gst/fullpage.html?res= 9401E0DB1139F935A35750C0A9649D8B63.
55. Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy 2003;23:871-80. (Pubitemid 36875671)
56. Cucchiara B, Kasner SE. Use of statins in CNS disorders. J Neurol Sci 2001;187:81-9. (Pubitemid 32611661)
57. 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. (Pubitemid 35379733)
58. Trompet S, van Vliet P, de Craen AJ, Jolles J, Buckley BM, Murphy MB, et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J Neurol 2010;257:85-90.
59. Swiger KJ, Manalac RJ, Blumenthal RS, Blaha MJ, Martin SS. Statins and cognition: a systematic review and meta-analysis of short- and long-term cognitive effects. Mayo Clin Proc 2013;88:1213-21.
60. Richardson K, Schoen M, French B, Umscheid CA, Mitchell MD, Arnold SE, et al. Statins and cognitive function: a systematic review. Ann Intern Med 2013;159:688-97.
61. Summers MJ, Oliver KR, Coombes JS, Fassett RG. Effect of atorvastatin on cognitive function in patients from the Lipid Lowering and Onset of Renal Disease (LORD) trial. Pharmacotherapy 2007;27:183-90. (Pubitemid 46214578)
62. Kaba NK, Francis CW, Moss AJ, Zareba W, Oakes D, Knox KL, et al. Effects of lipids and lipid-lowering therapy on hemostatic factors in patients with myocardial infarction. J Thromb Haemost 2004;2:718-25. (Pubitemid 40185709)
63. Glynn RJ, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med 2009;360:1851-61.
64. Freeman DJ, Robertson M, Brown EA, Rumley A, Tobias ES, Frölich M, et al. Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). BMC Geriatr 2011;11:8.
65. Tumlin J, Stacul F, Adam A, Becker CR, Davidson C, Lameire N, et al. Pathophysiology of contrast-induced nephropathy. Am J Cardiol 2006;98:14K-20K.
66. McCullough PA, Khambatta S, Jazrawi A. Minimizing the renal toxicity of iodinated contrast. Circulation 2011;124:1210-1.
67. Li Y, Liu Y, Fu L, Mei C, Dai B. Efficacy of short-term high-dose statin in preventing contrast-induced nephropathy: a meta-analysis of seven randomized controlled trials. PLoS One 2012;7:e34450.
68. Quintavalle C, Fiore D, De Micco F, Visconti G, Focaccio A, Golia B, et al. Impact of a high loading dose of atorvastatin on contrast-induced acute kidney injury. Circulation 2012;126:3008-16.
69. Leoncini M, Toso A, Maioli M, Tropeano F, Villani S, Bellandi F. Early high-dose rosuvastatin for contrast-induced nephropathy prevention in acute coronary syndrome. Results from Protective effect of Rosuvastatin and Antiplatelet Therapy On contrast-induced acute kidney injury and myocardial damage in patients with Acute Coronary Syndrome (PRATO-ACS Study). J Am Coll Cardiol 2014;63:71-9.
70. Roberts M. CRESTOR (Rosuvastatin calcium) NDA 21-366 JUPITER. United States Food and Drug Administration Endocrinologic and Metabolic Drugs Advisory Committee. 2009. www.fda.gov/downloads/advisorycommittees/ committeesmeetingmaterials/drugs/ endocrinologicandmetabolicdrugsadvisorycommittee/ucm194918.pdf.
71. Dormuth CR, Hemmelgarn BR, Paterson JM, James MT, Teare GF, Raymond CB, et al. Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases. BMJ 2013;346:f880.
72. Duane WC, Hunninghake DB, Freeman ML, Pooler PA, Schlasner LA, Gebhard RL. Simvastatin, a competitive inhibitor of HMG-CoA reductase, lowers cholesterol saturation index of gallbladder bile. Hepatology 1988;8:1147-50.
73. Preiss D, Tikkanen MJ, Welsh P, Ford I, Lovato LC, Elam MB, et al. Lipid-modifying therapies and risk of pancreatitis: a meta-analysis. JAMA 2012;308:804-11.
74. La Vignera S, Condorelli RA, Vicari E, Calogero AE. Statins and erectile dysfunction: a critical summary of current evidence. J Androl 2012;33:552-8.
75. Fibbi B, Morelli A, Marini M, Zhang XH, Mancina R, Vignozzi L, et al. Atorvastatin but not elocalcitol increases sildenafil responsiveness in spontaneously hypertensive rats by regulating the RhoA/ROCK pathway. J Androl 2008;29:70-84.
76. Corona G, Boddi V, Balercia G, Rastrelli G, De Vita G, Sforza A, et al. The effect of statin therapy on testosterone levels in subjects consulting for erectile dysfunction. J Sex Med 2010;7:1547-56.
77. Trivedi D, Kirby M, Wellsted DM, Ali S, Hackett G, O'Connor B, et al. Can simvastatin improve erectile function and health-related quality of life in men aged ?40 years with erectile dysfunction? Results of the Erectile Dysfunction and Statins Trial (ISRCTN66772971). BJU Int 2013;111:324-33.
78. Walsh GM. Statins as emerging treatments for asthma and chronic obstructive pulmonary disease. Expert Rev Respir Med 2008;2:329-35. (Pubitemid 351959392)
79. Lee JH, Lee DS, Kim EK, Choe KH, Oh YM, Shim TS, et al. Simvastatin inhibits cigarette smoking-induced emphysema and pulmonary hypertension in rat lungs. Am J Respir Crit Care Med 2005;172:987-93.
80. Lee SJ, Sacks FM. Effect of pravastatin on intermediate-density and low-density lipoproteins containing apolipoprotein CIII in patients with diabetes mellitus. Am J Cardiol 2003;92:121-4. (Pubitemid 36835957)
81. Moosavi SA, Raji H, Faghankhani M, Yazdani R, Esmaeili M. Evaluation of the effects of atorvastatin on the treatment of secondary pulmonary hypertension due to chronic obstructive pulmonary diseases: a randomized controlled trial. Iran Red Crescent Med J 2013;15:649-54.
82. Janda S, Park K, FitzGerald JM, Etminan M, Swiston J. Statins in COPD: a systematic review. Chest 2009;136:734-43.
83. 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. (Pubitemid 26338729)
84. Emberson JR, Kearney PM, Blackwell L, Newman C, Reith C, Bhala N, et al. Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175 000 people in 27 randomised trials of statin therapy. PLoS One 2012;7:e29849.
85. Hsia J, MacFadyen JG, Monyak J, Ridker PM. 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 2011;57:1666-75.
86. Wardle J, Armitage J, Collins R, Wallendszus K, Keech A, Lawson A. Randomised placebo controlled trial of effect on mood of lowering cholesterol concentration. Oxford Cholesterol Study Group. BMJ 1996;313:75-8. (Pubitemid 26257756)
87. Golomb BA, Evans MA, Dimsdale JE, White HL. Effects of statins on energy and fatigue with exertion: results from a randomized controlled trial. Arch Intern Med 2012;172:1180-2.
88. Perez AC, Jhund P, Preiss D, Kjekshus J, McMurray JJ. Effect of rosuvastatin on fatigue in patients with heart failure. J Am Coll Cardiol 2013;61:1121-2.
89. Joy TR MA, Zou GY, Hegele RA, McDonald CG, Mahon JL. N-of-1 (single-patient) trials for statin-related myalgia. Ann Intern Med 2014;160:301-10.
90. Pencina MJ, Navar-Boggan AM, D'Agostino RB Sr, Williams K, Neely B, Sniderman AD, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med 2014;370:1422-31.
91. Hayward RA, Hofer TP, Vijan S. Narrative review: lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem. Ann Intern Med 2006;145:520-30. (Pubitemid 46780956)
92. Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart survey. Chest 2010;138:1093-100.
93. Falagas ME, Makris GC, Matthaiou DK, Rafailidis PI. Statins for infection and sepsis: a systematic review of the clinical evidence. J Antimicrob Chemother 2008;61:774-85. (Pubitemid 351426059)
94. Papazian L, Roch A, Charles PE, Penot-Ragon C, Perrin G, Roulier P, et al. Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: a randomized clinical trial. JAMA 2013;310:1692-700.
95. Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006;354:1264-72.
96. Sullivan D, Olsson AG, Scott R, Kim JB, Xue A, Gebski V, et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA 2012;308:2497-506.