Statin intolerance: Now a solved problem

Journal of Postgraduate Medicine

Volumn 57, Issue 4, 2011, Pages 321-328

  Sikka, P ^a   Kapoor, S ^b   Bindra, V K ^c   Sharma, M ^a   Vishwakarma, P ^a   Saxena, K K ^a  

^a LLRM MEDICAL COLLEGE   (India)

^b ITS CDSR ^*  (India)

^c IDST   (India)

Author keywords

Hepatotoxicity; intolerance; management; myopathy; statins

Indexed keywords

AMIODARONE; ANTIFUNGAL AGENT; APOLIPOPROTEIN B100; ATORVASTATIN; BEZAFIBRATE; CHOLESTIN; COLESTIPOL; COLESTYRAMINE; CYCLOSPORIN; EZETIMIBE; FENOFIBRATE; FIBRIC ACID DERIVATIVE; FLUINDOSTATIN; GEMFIBROZIL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; MACROLIDE; MEVINOLIN; MIPOMERSEN; NEFAZODONE; NICOTINIC ACID; PEGINTERFERON; PLACEBO; PRAVASTATIN; RIBAVIRIN; ROSUVASTATIN; SIMVASTATIN; UBIDECARENONE; UNINDEXED DRUG; VERAPAMIL; VITAMIN D;

APHERESIS; DRUG DOSE REDUCTION; DRUG HYPERSENSITIVITY; DRUG WITHDRAWAL; DYSLIPIDEMIA; DYSPEPSIA; FLUSHING; GENETIC PREDISPOSITION; HEPATITIS C; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; HYPOLIPEMIA; LIFESTYLE MODIFICATION; LIVER FUNCTION; LIVER TOXICITY; LOW DRUG DOSE; MYALGIA; MYOPATHY; NEUROPATHY; POSTMARKETING SURVEILLANCE; REVIEW; RHABDOMYOLYSIS; SIDE EFFECT; SUPPLEMENTATION;

ANTICHOLESTEREMIC AGENTS; DIETARY SUPPLEMENTS; DRUG-INDUCED LIVER INJURY; FIBRIC ACIDS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPERLIPIDEMIAS; LIFE STYLE; MUSCULAR DISEASES; NIACIN; UBIQUINONE; VITAMIN D;

EID: 84855240102     PISSN: 00223859     EISSN: 09722823     Source Type: Journal    
DOI: 10.4103/0022-3859.90085     Document Type: Review

References (80)

1. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-9.
2. Mahley RW, Bersot TP. Drug therapy for hypercholesterolemia and dyslipidemia. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman and Gilman's the pharmacological basis of therapeutics, 11th ed. New Delhi: McGraw Hill; 2006. p. 933-66.
3. Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005;45:89-118. (Pubitemid 40261799)
4. Armitage J. The safety of statins in clinical practice. Lancet 2007;370:1781-90. (Pubitemid 350137473)
5. Jacobson TA. Toward "pain-free" statin prescribing: Clinical algorithm for diagnosis and management of myalgia. Mayo Clin Proc 2008;83:687-700. (Pubitemid 351810569)
6. Vandenberg BF, Robinson J. Management of the patient with statin intolerance. Curr Atheroscler Rep 2010;12:48-57.
7. Omar MA, Wilson JP, Cox TS. Rhabdomyolysis and HMG-CoA reductase inhibitors. Ann Pharmacother 2001;35:1096-107. (Pubitemid 32880030)
8. 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. Circulation 2002;106:1024-8. (Pubitemid 34925341)
9. Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA 2003;289:1681-90. (Pubitemid 37430274)
10. Law M, Rudnicka AR. Statin safety: A systematic review. Am J Cardiol 2006;97: S52-60.
11. Davidson MH, Robinson JG. Safety of aggressive lipid management. J Am Coll Cardiol 2007;49:1753-62. (Pubitemid 46617861)
12. 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)
13. Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: Systematic review and meta-analysis. BMJ 2003;326:1423.
14. Maiese LM. The statin hepatotoxicity myth. Heartbeat 2010;145:1-2.
15. Cohen D, Anania F, Chalasani N. An assessment of statin safety by hepatologists. Am J Cardiol 2006;97: C77-81.
16. Tolman KG. Defining patient risks from expanded preventive therapies. Am J Cardiol 2000;85:15E-9E.
17. de Denus S, Spinler SA, Miller K, Peterson AM. Statins and liver toxicity: A meta-analysis. Pharmacotherapy 2004;24:584-91. (Pubitemid 38585952)
18. Madhoun MF, Bader T. Statins improve ALT values in chronic hepatitis C patients with abnormal values. Dig Dis Sci 2010;55:870-1.
19. Bader T, Fazili J, Madhoun M, Aston C, Hughes D, Rizvi S, et al. Fluvastatin inhibits hepatitis C replication in humans. Am J Gastroenterol 2008;103:1383-9. (Pubitemid 351813920)
20. Abraldes JG, Albillos A, Bañares R, Turnes J, González R, García-Pagán JC, et al. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: A randomized controlled trial. Gastroenterology 2009;136:1651-8.
21. 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)
22. Joy TR, Hegele RA. Narrative review: Statin-related myopathy. Ann Intern Med 2009;150:858-68.
23. Baker SK, Samjoo IA. A neuromuscular approach to statin-related myotoxicity. Can J Neurol Sci 2008;35:8-21.
24. Ray GM. Antiretroviral and statin drug-drug interactions. Cardiol Rev 2009;17:44-7.
25. Fichtenbaum CJ, Gerber JG, Rosenkranz SL, Segal Y, Aberg JA, Blaschke T, et al. Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047. AIDS 2002;16:569-77. (Pubitemid 34218852)
26. Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: Mechanisms and clinical relevance. Clin Pharmacol Ther 2006;80:565-81. (Pubitemid 44908269)
27. Kyrklund C, Backman JT, Kivistö KT, Neuvonen M, Laitila J, Neuvonen PJ. Plasma concentrations of active lovastatin acid are markedly increased by gemfibrozil but not by bezafibrate. Clin Pharmacol Ther 2001;69:340-5. (Pubitemid 32477075)
28. Kyrklund C, Backman JT, Neuvonen M, Neuvonen PJ. Gemfibrozil increases plasma pravastatin concentrations and reduces pravastatin renal clearance. Clin Pharmacol Ther 2003;73:538-44. (Pubitemid 37249124)
29. Schneck DW, Birmingham BK, Zalikowski JA, Mitchell PD, Wang Y, Martin PD, et al. The effect of gemfibrozil on the pharmacokinetics of rosuvastatin. Clin Pharmacol Ther 2004;75:455-63. (Pubitemid 38534566)
30. Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate-statin versus gemfibrozil-any statin. Am J Cardiol 2005;95:120-2. (Pubitemid 40051126)
31. Becquemont L, Neuvonen M, Verstuyft C, Jaillon P, Letierce A, Neuvonen PJ, et al. Amiodarone interacts with simvastatin but not with pravastatin disposition kinetics. Clin Pharmacol Ther 2007;81:679-84. (Pubitemid 46625102)
32. SEARCH Collaborative Group, Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, et al. SLCO1B1 variants and statin-induced myopathy-a genome wide study. N Engl J Med 2008;359:789-99.
33. Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, et al. A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem 1999;274:37161-8.
34. Schneck DW, Birmingham BK, Zalikowski JA, Mitchell PD, Wang Y, Martin PD, et al. The effect of gemfibrozil on the pharmacokinetics of rosuvastatin. Clin Pharmacol Ther 2004;75:455-63. (Pubitemid 38534566)
35. Bellosta S, Paoletti R, Corsini A. Safety of statins: Focus on clinical pharmacokinetics and drug interactions. Circulation 2004;109(23 Suppl 1): III50-7. (Pubitemid 38786444)
36. Fiegenbaum M, da Silveira FR, Van der Sand CR, Van der Sand LC, Ferreira ME, Pires RC, et al. The role of common variants of ABCB1, CYP3A4, and CYP3A5genes in lipid-lowering efficacy and safety of simvastatin treatment. Clin Pharmacol Ther 2005;78:551-8. (Pubitemid 41698910)
37. Frudakis TN, Thomas MJ, Ginjupalli SN, Handelin B, Gabriel R, Gomez HJ. CYP2D6*4 polymorphism is associated with statin-induced muscle effects. Pharmacogenet Genomics 2007;17:695-707. (Pubitemid 47263065)
38. Hermann M, Bogsrud MP, Molden E, Asberg A, Mohebi BU, Ose L, et al. Exposure of atorvastatin is unchanged but lactone and acid metabolites are increased several-fold in patients with atorvastatin-induced myopathy. Clin Pharmacol Ther 2006;79:532-9. (Pubitemid 43833450)
39. Mulder AB, van Lijf HJ, Bon MA, van den Bergh FA, Touw DJ, Neef C, et al. Association of polymorphism in the cytochrome CYP2D6 and the efficacy and tolerability of simvastatin. Clin Pharmacol Ther 2001;70:546-51. (Pubitemid 34008412)
40. Zuccaro P, Mombelli G, Calabresi L, Baldassarre D, Palmi I, Sirtori CR. Tolerability of statins is not linked to CYP450 polymorphisms, but reduced CYP2D6 metabolism improves cholesteraemic response to simvastatin and fluvastatin. Pharmacol Res 2007;55:310-7. (Pubitemid 46518161)
41. Oh J, Ban MR, Miskie BA, Pollex RL, Hegele RA. Genetic determinants of statin intolerance. Lipids Health Dis 2007;6:7.
42. Ruaño G, Thompson PD, Windemuth A, Seip RL, Dande A, Sorokin A, et al. Physiogenomic association of statin-related myalgia to serotonin receptors. Muscle Nerve 2007;36:329-35. (Pubitemid 47326011)
43. Dolley G, Lamarche B, Després JP, Bouchard C, Pérusse L, Vohl MC. Phosphoinositide cycle gene polymorphisms affect the plasma lipid profile in the Quebec Family Study. Mol Genet Metab 2009;97:149-54.
44. Day JW, Ranum LP. Genetics and molecular pathogenesis of the myotonic dystrophies. Curr Neurol Neurosci Rep 2005;5:55-9.
45. Sathasivam S, Lecky B. Statin induced myopathy. BMJ 2008;337: A2286.
46. 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;97:89C-94C.
47. Hansen KE, Hildebrand JP, Ferguson EE, Stein JH. Outcomes in 45 patients with statin-associated myopathy. Arch Intern Med 2005;165:2671-6. (Pubitemid 41785067)
48. Stein EA, Ballantyne CM, Windler E, Sirnes PA, Sussekov A, Yigit Z, et al. Efficacy and tolerability of fluvastatin XL 80 mg alone, ezetimibe alone, and the combination of fluvastatin XL 80 mg with ezetimibe in patients with a history of muscle-related side effects with other statins. Am J Cardiol 2008;101:490-6. (Pubitemid 351199443)
49. Glueck CJ, Aregawi D, Agloria M, Khalil Q, Winiarska M, Munjal J, et al. Rosuvastatin 5 and 10 mg/d: A pilot study of the effects in hypercholesterolemic adults unable to tolerate other statins and reach LDL cholesterol goals with nonstatin lipid-lowering therapies. Clin Ther 2006;28:933-42. (Pubitemid 44062693)
50. Bruckert E, Hayem G, Dejager S, Yau C, Bégaud 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)
51. Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med 2002;346:539-40.
52. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med 2009;361:62-72.
53. 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 (STELLA.R.* Trial). Am J Cardiol 2003;92:152-60. (Pubitemid 36835963)
54. 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;144:674-7.
55. Athyros VG, Tziomalos K, Gossios TD, Griva T, Anagnostis P, Kargiotis K, 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;376:1916-22.
56. Backes JM, Venero CV, Gibson CA, Ruisinger JF, Howard PA, Thompson PD, et al. Effectiveness and tolerability of every-other-day rosuvastatin dosing in patients with prior statin intolerance. Ann Pharmacother 2008;42:341-6. (Pubitemid 351429598)
57. Backes JM, Moriarty PM, Ruisinger JF, Gibson CA. Effects of once weekly rosuvastatin among patients with a prior statin intolerance. Am J Cardiol 2007;100:554-5.
58. Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A 2005;102:8132-7. (Pubitemid 40800055)
59. Gagné C, Bays HE, Weiss SR, Mata P, Quinto K, Melino M, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol 2002;90:1084-91. (Pubitemid 35339435)
60. Knopp RH, Dujovne CA, Le Beaut A, Lipka LJ, Suresh R, Veltri EP. Evaluation of the efficacy, safety, and tolerability of ezetimibe in primary hypercholesterolaemia: A pooled analysis from two controlled phase III clinical studies. Int J Clin Pract 2003;57:363-8. (Pubitemid 36798442)
61. Bays HE, Goldberg RB, Truitt KE, Jones MR. Colesevelam hydrochloride therapy in patients with type 2 diabetes mellitus treated with metformin: Glucose and lipid effects. Arch Intern Med 2008;168: 1975-83.
62. Knopp RH, Ginsberg J, Albers JJ, Hoff C, Ogilvie JT, Warnick GR, et al. Contrasting effects of unmodified and time-release forms of niacin on lipoproteins in hyperlipidemic subjects: Clues to mechanism of action of niacin. Metabolism 1985;34:642-50. (Pubitemid 15036921)
63. Henkin Y, Oberman A, Hurst DC, Segrest JP. Niacin revisited: Clinical observations on an important but underutilized drug. Am J Med 1991;91:239-46.
64. Schwartz ML. Severe reversible hyperglycemia as a consequence of niacin therapy. Arch Intern Med 1993;153:2050-2. (Pubitemid 23263568)
65. Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature 2000;405:421-4. (Pubitemid 30367411)
66. Watts GF, Dimmitt SB. Fibrates, dyslipoproteinaemia and cardiovascular disease. Curr Opin Lipidol 1999;10:561-74. (Pubitemid 30064026)
67. Thompson GR. Recommendations for the use of LDL apheresis. Atherosclerosis 2008;198:247-55.
68. Thompson GR, Barbir M, Davies D, Dobral P, Gesinde M, Livingston M, et al. Efficacy criteria and cholesterol targets for LDL apheresis. Atherosclerosis 2010;208:317-21.
69. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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) final report. Circulation 2002;106:3143-421.
70. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002;106: 2747-57. (Pubitemid 35364932)
71. Grundy SM, Cleeman JI, Merz CN, 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. (Pubitemid 38924592)
72. Jenkins DJ, Wong JM, Kendall CW, Esfahani A, Ng VW, Leong TC, et al. The effect of a plantbased low-carbohydrate ("Eco-Atkins") diet on body weight and blood lipid concentrations in hyperlipidemic subjects. Arch Intern Med 2009;169:1046-54.
73. Becker DJ, Gordon RY, Halbert SC, French B, Morris PB, Rader DJ. Red yeast rice for dyslipidemia in statin-intolerant patients: A randomized trial. Ann Intern Med 2009;150:830-9.
74. Becker DJ, Gordon RY, Morris PB, Yorko J, Gordon YJ, Li M, et al. Simvastatin vs therapeutic lifestyle changes and supplements: Randomized primary prevention trial. Mayo Clin Proc 2008;83:758-64. (Pubitemid 351948689)
75. Lee JH, O'Keefe JH, Bell D, Hensrud DD, Holick MF. Vitamin D deficiency an important, common, and easily treatable cardiovascular risk factor? J Am Coll Cardiol 2008;52:1949-56.
76. Crooke RM, Graham MJ, Lemonidis KM, Whipple CP, Koo S, Perera RJ. An apolipoprotein B antisense oligonucleotide lowers LDL cholesterol in hyperlipidemic mice without causing hepatic steatosis. J Lipid Res 2005;46:872-84.
77. Raal FJ, Santos RD, Blom DJ, Marais AD, Charng MJ, Cromwell WC, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: A randomised, double-blind, placebo-controlled trial. Lancet 2010;375:998-1006.
78. Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med 2007;356:148-56. (Pubitemid 46089675)
79. Bloomfield D, Carlson GL, Sapre A, Tribble D, McKenney JM, Littlejohn TW 3rd, et al. Efficacy and safety of the cholesteryl ester transfer protein inhibitor anacetrapib asmonotherapy and coadministered with atorvastatin in dyslipidemic patients. Am Heart J 2009;157:352-60.
80. 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.