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Canadian Journal of Cardiology

Diagnosis, Prevention, and Management of Statin Adverse Effects and Intolerance: Canadian Consensus Working Group Update (2016)

Published:January 13, 2016DOI:https://doi.org/10.1016/j.cjca.2016.01.003

      Abstract

      The Canadian Consensus Working Group has updated its evaluation of the literature pertaining to statin intolerance and adverse effects. This overview introduces a pragmatic definition of statin intolerance (goal-inhibiting statin intolerance) that emphasizes the effects of symptoms on achieving nationally vetted goals in patients fulfilling indications for lipid-lowering therapy and cardiovascular risk reduction. The Canadian Consensus Working Group provides a structured framework for avoiding, evaluating and managing goal-inhibiting statin intolerance. Particularly difficult practice situations are reviewed, including management in young and elderly individuals, and in athletes and labourers. Finally, targeted at specialty practitioners, more detailed analyses of specific but more unusual adverse effects ascribed to statins are updated including evidence regarding new-onset diabetes, cognitive dysfunction, cataracts, and the rare but important immune-mediated necrotizing myopathy.

      Résumé

      Le Canadian Consensus Working Group a mis à jour son évaluation de la littérature concernant l’intolérance et les effets indésirables des statines. Cet aperçu présente une définition pragmatique de l’intolérance aux statines (intolérance aux statines GISI) qui souligne les effets des symptômes sur l’atteinte des objectifs approuvés à l’échelon national chez les patients qui remplissent les indications de traitement hypolipidémiant et de réduction du risque cardiovasculaire. Le Canadian Consensus Working Group offre un cadre structuré pour éviter, évaluer et prendre en charge l’intolérance aux statines GISI. Nous passons en revue des situations particulièrement difficiles dans la pratique, dont la prise en charge des individus jeunes et âgés, des athlètes et des ouvriers. Finalement, destinées aux praticiens spécialistes, des analyses plus détaillées sur les effets secondaires particuliers, mais plus inhabituels attribués aux statines sont mises à jour, y compris les données probantes concernant le diabète de novo, le dysfonctionnement cognitif, les cataractes, et la rare, mais importante, myopathie nécrosante immunomédiée.
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      References

        • Mancini G.B.
        • Baker S.
        • Bergeron J.
        • et al.
        Diagnosis, prevention, and management of statin adverse effects and intolerance: proceedings of a Canadian Working Group Consensus Conference.
        Can J Cardiol. 2011; 27: 635-662
        • Mancini G.B.
        • Tashakkor A.Y.
        • Baker S.
        • et al.
        Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Working Group Consensus Update.
        Can J Cardiol. 2013; 29: 1553-1568
        • Brewster L.M.
        • Mairuhu G.
        • Sturk A.
        • van Montfrans G.A.
        Distribution of creatine kinase in the general population: implications for statin therapy.
        Am Heart J. 2007; 154: 655-661
        • Maji D.
        • Shaikh S.
        • Solanki D.
        • Gaurav K.
        Safety of statins.
        Indian J Endocrinol Metab. 2013; 17: 636-646
        • Ahmad Z.
        Statin intolerance.
        Am J Cardiol. 2014; 113: 1765-1771
        • 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. 2014; 8: S47-S57
        • Desai C.S.
        • Martin S.S.
        • Blumenthal R.S.
        Non-cardiovascular effects associated with statins.
        BMJ. 2014; 349: g3743
        • Guyton J.R.
        • Bays H.E.
        • Grundy S.M.
        • Jacobson T.A.
        An assessment by the Statin Intolerance Panel: 2014 update.
        J Clin Lipidol. 2014; 8: S72-S81
        • Jacobson T.A.
        NLA Task Force on Statin Safety - 2014 update.
        J Clin Lipidol. 2014; 8: S1-S4
        • Katz D.H.
        • Intwala S.S.
        • Stone N.J.
        Addressing statin adverse effects in the clinic: the 5 Ms.
        J Cardiovasc Pharmacol Ther. 2014; 19: 533-542
        • Maki K.C.
        • Ridker P.M.
        • Brown W.V.
        • Grundy S.M.
        • Sattar N.
        An assessment by the Statin Diabetes Safety Task Force: 2014 update.
        J Clin Lipidol. 2014; 8: S17-S29
        • Mlodinow S.G.
        • Onysko M.K.
        • Vandiver J.W.
        • Hunter M.L.
        • Mahvan T.D.
        Statin adverse effects: sorting out the evidence.
        J Fam Pract. 2014; 63: 497-506
        • Naderi S.
        • Cho L.
        Statin intolerance: diagnosis, treatment and alternative therapies.
        Clin Lipidol. 2014; 9: 355-367
        • Patnaik S.
        • Patnaik A.N.
        Management of dyslipidaemia in statin-intolerant patients in light of AHA and NPA guidelines of 2013–2014.
        J Indian Coll Cardiol. 2015; 5: 119-122
        • Ramsey L.B.
        • Johnson S.G.
        • Caudle K.E.
        • et al.
        The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update.
        Clin Pharmacol Ther. 2014; 96: 423-428
        • Reiner Z.
        Resistance and intolerance to statins.
        Nutr Metab Cardiovasc Dis. 2014; 10: 1057-1066
        • Rojas-Fernandez C.H.
        • Goldstein L.B.
        • Levey A.I.
        • Taylor B.A.
        • Bittner V.
        An assessment by the Statin Cognitive Safety Task Force: 2014 update.
        J Clin Lipidol. 2014; 8: S5-S16
        • Rosenson R.S.
        • Baker S.K.
        • Jacobson T.A.
        • Kopecky S.L.
        • Parker B.A.
        An assessment by the Statin Muscle Safety Task Force: 2014 update.
        J Clin Lipidol. 2014; 8: S58-S71
        • Sirtori C.R.
        The pharmacology of statins.
        Pharmacol Res. 2014; 88: 3-11
        • Banach M.
        • Rizzo M.
        • Toth P.P.
        • et al.
        Statin intolerance - an attempt at a unified definition. Position paper from an International Lipid Expert Panel.
        Arch Med Sci. 2015; 11: 1-23
        • Birtcher K.
        When compliance is an issue-how to enhance statin adherence and address adverse effects.
        Curr Atheroscler Rep. 2015; 17: 471
        • Fitchett D.H.
        • Hegele R.A.
        • Verma S.
        Statin intolerance.
        Circulation. 2015; 131: e389-e391
        • Gulum A.H.
        • Hume A.L.
        Statins: an update on clinical issues and selected adverse effects.
        Jpn J Nurse Pract. 2015; 11: 287-294
        • Kopecky S.
        • Baum S.
        • Foody J.M.
        • et al.
        Insights into statin intolerance.
        Clin Cardiol. 2015; 38: 520-526
        • Pirillo A.
        • Catapano A.L.
        Statin intolerance: diagnosis and remedies.
        Curr Cardiol Rep. 2015; 17: 27
        • Stroes E.S.
        • Thompson P.D.
        • Corsini A.
        • et al.
        Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management.
        Eur Heart J. 2015; 36: 1012-1022
        • Stulc T.
        • Ceska R.
        • Gotto Jr., A.M.
        Statin intolerance: the clinician's perspective.
        Curr Atheroscler Rep. 2015; 17: 69
        • Yuet W.C.
        • Khine H.
        • Ahmad Z.
        Statin-associated adverse events.
        Clin Med Insights Ther. 2015; 7: 17-24
        • Gryn S.E.
        • Hegele R.A.
        Pharmacogenomics, lipid disorders and treatment options.
        Clin Pharmacol Ther. 2014; 96: 36-47
        • Needham M.
        • Mastaglia F.L.
        Statin myotoxicity: a review of genetic susceptibility factors.
        Neuromuscul Disord. 2014; 24: 4-15
        • Patel J.
        • Superko H.R.
        • Martin S.S.
        • Blumenthal R.S.
        • Christopher-Stine L.
        Genetic and immunologic susceptibility to statin-related myopathy.
        Atherosclerosis. 2015; 240: 260-271
        • Link E.
        • Parish S.
        • et al.
        • SEARCH Collaborative Group
        SLCO1B1 variants and statin-induced myopathy–a genomewide study.
        N Engl J Med. 2008; 359: 789-799
        • Mangravite L.M.
        • Engelhardt B.E.
        • Medina M.W.
        • et al.
        A statin-dependent QTL for GATM expression is associated with statin-induced myopathy.
        Nature. 2013; 502: 377-380
        • Floyd J.S.
        • Bis J.C.
        • Brody J.A.
        • et al.
        GATM locus does not replicate in rhabdomyolysis study.
        Nature. 2014; 513: E1-E3
        • Luzum J.A.
        • Kitzmiller J.P.
        • Isackson P.J.
        • et al.
        GATM polymorphism associated with the risk for statin-induced myopathy does not replicate in case-control analysis of 715 dyslipidemic individuals.
        Cell Metab. 2015; 21: 622-627
        • DeGorter M.K.
        • Tirona R.G.
        • Schwarz U.I.
        • et al.
        Clinical and pharmacogenetic predictors of circulating atorvastatin and rosuvastatin concentrations in routine clinical care.
        Circ Cardiovasc Genet. 2013; 6: 400-408
        • Vladutiu G.D.
        • Isackson P.J.
        • Kaufman K.
        • et al.
        Genetic risk for malignant hyperthermia in non-anesthesia-induced myopathies.
        Mol Genet Metab. 2011; 104: 167-173
        • Greville-Harris M.
        • Dieppe P.
        Bad is more powerful than good: the nocebo response in medical consultations.
        Am J Med. 2015; 128: 126-129
        • Olshansky B.
        Placebo and nocebo in cardiovascular health: implications for healthcare, research, and the doctor-patient relationship.
        J Am Coll Cardiol. 2007; 49: 415-421
        • Häuser W.
        • Hansen E.
        • Enck P.
        Nocebo phenomena in medicine: their relevance in everyday clinical practice.
        Dtsch Arztebl Int. 2012; 109: 459-465
        • Data-Franco J.
        • Berk M.
        The nocebo effect: a clinicians guide.
        Aust N Z J Psychiatry. 2013; 47: 617-623
        • Faasse K.
        • Petrie K.J.
        The nocebo effect: patient expectations and medication side effects.
        Postgrad Med J. 2013; 89: 540-546
        • Arnold M.H.
        • Finniss D.G.
        • Kerridge I.
        Medicine's inconvenient truth: the placebo and nocebo effect.
        Intern Med J. 2014; 44: 398-405
        • Bingel U.
        Avoiding nocebo effects to optimize treatment outcome.
        JAMA. 2014; 312: 693-694
        • Finegold J.A.
        • Manisty C.H.
        • Goldacre B.
        • Barron A.J.
        • Francis D.P.
        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; 21: 464-474
        • Jakovljevic M.
        The placebo-nocebo response: controversies and challenges from clinical and research perspective.
        Eur Neuropsychopharmacol. 2014; 24: 333-341
        • Petersen G.L.
        • Finnerup N.B.
        • Colloca L.
        • et al.
        The magnitude of nocebo effects in pain: a meta-analysis.
        Pain. 2014; 155: 1426-1434
        • Tan K.
        • Petrie K.J.
        • Faasse K.
        • Bolland M.J.
        • Grey A.
        Unhelpful information about adverse drug reactions.
        BMJ. 2014; 349: g5019
        • Crichton F.
        • Petrie K.J.
        Accentuate the positive: counteracting psychogenic responses to media health messages in the age of the Internet.
        J Psychosom Res. 2015; 79: 185-189
        • Frisaldi E.
        • Piedimonte A.
        • Benedetti F.
        Placebo and nocebo effects: a complex interplay between psychological factors and neurochemical networks.
        Am J Clin Hypn. 2015; 57: 267-284
        • Symon A.
        • Williams B.
        • Adelasoye Q.A.
        • Cheyne H.
        Nocebo and the potential harm of ‘high risk’ labelling: a scoping review.
        J Adv Nurs. 2015; 71: 1518-1529
      1. Tobert JA, Newman CB. Statin tolerability: in defence of placebo-controlled trials. Eur J Prev Cardiol 2016;23:891-6.

        • Rouhi-Boroujeni H.
        • Rouhi-Boroujeni H.
        • Heidarian E.
        • Mohammadizadeh F.
        • Rafieian-Kopaei M.
        Herbs with anti-lipid effects and their interactions with statins as a chemical anti- hyperlipidemia group drugs: a systematic review.
        ARYA Atheroscler. 2015; 11: 244-251
        • Skarlovnik A.
        • Janic M.
        • Lunder M.
        • Turk M.
        • Sabovic M.
        Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study.
        Med Sci Monit. 2014; 20: 2183-2188
        • Taylor B.A.
        • Lorson L.
        • White C.M.
        • Thompson P.D.
        A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy.
        Atherosclerosis. 2015; 238: 329-335
        • Banach M.
        • Serban C.
        • Sahebkar A.
        • et al.
        Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials.
        Mayo Clin Proc. 2015; 90: 24-34
        • Mergenhagen K.
        • Ott M.
        • Heckman K.
        • Rubin L.M.
        • Kellick K.
        Low vitamin D as a risk factor for the development of myalgia in patients taking high-dose simvastatin: a retrospective review.
        Clin Ther. 2014; 36: 770-777
        • Palamaner Subash Shantha G.
        • Ramos J.
        • Thomas-Hemak L.
        • Pancholy S.B.
        Association of vitamin D and incident statin induced myalgia–a retrospective cohort study.
        PLoS One. 2014; 9: e88877
        • Eisen A.
        • Lev E.
        • Iakobishvilli Z.
        • et al.
        Low plasma vitamin D levels and muscle-related adverse effects in statin users.
        Isr Med Assoc J. 2014; 16: 42-45
        • Ahmed W.
        • Khan N.
        • Glueck C.J.
        • et al.
        Low serum 25 (OH) vitamin D levels (< 32 ng/mL) are associated with reversible myositis-myalgia in statin-treated patients.
        Transl Res. 2009; 153: 11-16
        • Khayznikov M.
        • Hemachrandra K.
        • Pandit R.
        • et al.
        Statin intolerance because of myalgia, myositis, myopathy, or myonecrosis can in most cases be safely resolved by vitamin D supplementation.
        N Am J Med Sci. 2015; 7: 86-93
        • Lee P.
        • Greenfield J.R.
        • Campbell L.V.
        Vitamin D insufficiency - a novel mechanism of statin-induced myalgia?.
        Clin Endocrinol (Oxf). 2009; 71: 154-155
        • Gerards M.C.
        • Terlou R.J.
        • Yu H.
        • Koks C.H.
        • Gerdes V.E.
        Traditional Chinese lipid-lowering agent red yeast rice results in significant LDL reduction but safety is uncertain - a systematic review and meta-analysis.
        Atherosclerosis. 2015; 240: 415-423
        • Pirillo A.
        • Catapano A.L.
        Berberine, a plant alkaloid with lipid- and glucose-lowering properties: from in vitro evidence to clinical studies.
        Atherosclerosis. 2015; 243: 449-461
        • Derosa G.
        • Romano D.
        • D'Angelo A.
        • Maffioli P.
        Berberis aristata/Silybum marianum fixed combination (Berberol) effects on lipid profile in dyslipidemic patients intolerant to statins at high dosages: a randomized, placebo-controlled, clinical trial.
        Phytomedicine. 2015; 22: 231-237
        • Thompson P.D.
        • Rubino J.
        • Janik M.J.
        • et al.
        Use of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance.
        J Clin Lipidol. 2015; 9: 295-304
        • Hegele R.A.
        • Gidding S.S.
        • Ginsberg H.N.
        • et al.
        Nonstatin low-density lipoprotein-lowering therapy and cardiovascular risk reduction-statement from ATVB Council.
        Arterioscler Thromb Vasc Biol. 2015; 35: 2269-2280
        • Baigent C.
        • Landray M.J.
        • Reith 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. 2011; 377: 2181-2192
        • Cannon C.P.
        • Blazing M.A.
        • Giugliano R.P.
        • et al.
        Ezetimibe added to statin therapy after acute coronary syndromes.
        N Engl J Med. 2015; 372: 2387-2397
        • Keech A.
        • Simes R.J.
        • Barter P.
        • et al.
        Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial.
        Lancet. 2005; 366: 1849-1861
        • Gerstein H.C.
        • Miller M.E.
        • Byington R.P.
        • et al.
        Effects of intensive glucose lowering in type 2 diabetes.
        N Engl J Med. 2008; 358: 2545-2559
        • Boden W.E.
        • Probstfield J.L.
        • Anderson T.
        • et al.
        Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy.
        N Engl J Med. 2011; 365: 2255-2267
        • Landray M.J.
        • Haynes R.
        • Hopewell J.C.
        • et al.
        Effects of extended-release niacin with laropiprant in high-risk patients.
        N Engl J Med. 2014; 371: 203-212
        • Lee Y.H.
        • Kim M.J.
        • Choi C.I.
        • et al.
        Retrospective study on antihyperlipidemic efficacy and safety of simvastatin, ezetimibe and their combination in Korean adults.
        Arch Pharm Res. 2011; 34: 1331-1337
        • Suzuki H.
        • Watanabe Y.
        • Kumagai H.
        • Shuto H.
        Comparative efficacy and adverse effects of the addition of ezetimibe to statin versus statin titration in chronic kidney disease patients.
        Ther Adv Cardiovasc Dis. 2013; 7: 306-315
        • Makkar K.M.
        • Sanoski C.A.
        • Goldberg L.R.
        • Spinler S.A.
        An observational study of ezetimibe in cardiac transplant recipients receiving calcineurin inhibitors.
        Ann Pharmacother. 2013; 47: 1457-1462
        • Husain N.E.
        • Hassan A.T.
        • Elmadhoun W.M.
        • Ahmed M.H.
        Evaluating the safety of Liptruzet (ezetimibe and atorvastatin): what are the potential benefits beyond low-density lipoprotein cholesterol-lowering effect?.
        Expert Opin Drug Saf. 2015; 14: 1445-1455
        • Kusters D.M.
        • Caceres M.
        • Coll M.
        • et al.
        Efficacy and safety of ezetimibe monotherapy in children with heterozygous familial or nonfamilial hypercholesterolemia.
        J Pediatr. 2015; 166 (e1371-3): 1377-1384
        • Luo L.
        • Yuan X.
        • Huang W.
        • et al.
        Safety of coadministration of ezetimibe and statins in patients with hypercholesterolaemia: a meta-analysis.
        Intern Med J. 2015; 45: 546-557
        • Savarese G.
        • De Ferrari G.M.
        • Rosano G.M.
        • Perrone-Filardi P.
        Safety and efficacy of ezetimibe: a meta-analysis.
        Int J Cardiol. 2015; 201: 247-252
        • Serban M.C.
        • Banach M.
        • Mikhailidis D.P.
        Clinical implications of the IMPROVE-IT trial in the light of current and future lipid-lowering treatment options.
        Expert Opin Pharmacother. 2015; : 1-12
        • Thomopoulos C.
        • Skalis G.
        • Michalopoulou H.
        • Tsioufis C.
        • Makris T.
        Effect of low-density lipoprotein cholesterol lowering by ezetimibe/simvastatin on outcome incidence: overview, meta-analyses, and meta-regression analyses of randomized trials.
        Clin Cardiol. 2015; 38: 763-769
        • Rossebo A.B.
        • Pedersen T.R.
        • Boman K.
        • et al.
        Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis.
        N Engl J Med. 2008; 359: 1343-1356
        • Green A.
        • Ramey D.R.
        • Emneus M.
        • et al.
        Incidence of cancer and mortality in patients from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial.
        Am J Cardiol. 2014; 114: 1518-1522
        • Battaggia A.
        • Donzelli A.
        • Font M.
        • Molteni D.
        • Galvano A.
        Clinical efficacy and safety of ezetimibe on major cardiovascular endpoints: systematic review and meta-analysis of randomized controlled trials.
        PLoS One. 2015; 10: e0124587
        • Simard C.
        • Poirier P.
        Ezetimibe-associated myopathy in monotherapy and in combination with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.
        Can J Cardiol. 2006; 22: 141-144
        • Brahmachari B.
        • Chatterjee S.
        Myopathy induced by statinezetimibe combination: evaluation of potential risk factors.
        Indian J Pharmacol. 2015; 47: 563-564
        • Garcia-Valladares I.
        • Espinoza L.R.
        Ezetimibe-induced relapsing polymyositis.
        J Rheumatol. 2010; 37: 472
        • Bergeron N.
        • Phan B.A.
        • Ding Y.
        • Fong A.
        • Krauss R.M.
        Proprotein convertase subtilisin/kexin type 9 inhibition: a new therapeutic mechanism for reducing cardiovascular disease risk.
        Circulation. 2015; 132: 1648-1666
        • Sabatine M.S.
        • Giugliano R.P.
        • Wiviott S.D.
        • et al.
        Efficacy and safety of evolocumab in reducing lipids and cardiovascular events.
        N Engl J Med. 2015; 372: 1500-1509
        • Robinson J.G.
        • Farnier M.
        • Krempf M.
        • et al.
        Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.
        N Engl J Med. 2015; 372: 1489-1499
        • Sullivan D.
        • Olsson A.G.
        • Scott R.
        • 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: 2497-2506
        • Moriarty P.M.
        • Thompson P.D.
        • Cannon C.P.
        • et al.
        Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: the ODYSSEY ALTERNATIVE randomized trial.
        J Clin Lipidol. 2015; 9: 758-769
        • Gouni-Berthold I.
        • Berthold H.K.
        Mipomersen and lomitapide: two new drugs for the treatment of homozygous familial hypercholesterolemia.
        Atheroscler Suppl. 2015; 18: 28-34
        • Visser M.E.
        • Wagener G.
        • Baker B.F.
        • et al.
        Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial.
        Eur Heart J. 2012; 33: 1142-1149
        • Finks S.W.
        • Campbell J.D.
        Avoiding patient morbidity: updated statin drug interactions and risks for patient harm.
        Nurse Pract. 2014; 39: 45-51
        • Kellick K.A.
        • Bottorff M.
        • Toth P.P.
        A clinician's guide to statin drug-drug interactions.
        J Clin Lipidol. 2014; 8: S30-S46
        • Bastida C.
        • Also M.A.
        • Pericas J.M.
        • et al.
        Rhabdomyolysis and severe hepatotoxicity due to a drug-drug interaction between ritonavir and simvastatin. Could we use the most cost-effective statin in all human immunodeficiency virus-infected patients?.
        Enferm Infecc Microbiol Clin. 2014; 32 ([in Spanish]): 579-582
        • Kanter C.T.
        • Luin M.
        • Solas C.
        • Burger D.M.
        • Vrolijk J.M.
        Rhabdomyolysis in a hepatitis C virus infected patient treated with telaprevir and simvastatin.
        Ann Hepatol. 2014; 13: 452-455
        • Page S.R.
        • Yee K.C.
        Rhabdomyolysis in association with simvastatin and dosage increment in clarithromycin.
        Intern Med J. 2014; 44: 690-693
        • Ginanneschi F.
        • Volpi N.
        • Giannini F.
        • et al.
        Rhabdomyolysis in an elderly multitreated patient: multiple drug interactions after statin withdrawal.
        J Neurol Sci. 2014; 336: 284-287
        • Bland C.M.
        • Bookstaver P.B.
        • Lu Z.K.
        • et al.
        Musculoskeletal safety outcomes of patients receiving daptomycin with HMG-CoA reductase inhibitors.
        Antimicrob Agents Chemother. 2014; 58: 5726-5731
        • Golightly L.K.
        • Barber G.R.
        • Barron M.A.
        • Page 2nd, R.L.
        Statins and daptomycin: safety assessment of concurrent use and evaluation of drug interaction liability.
        Drug Metabol Drug Interact. 2013; 28: 49-58
        • Kido K.
        • Wheeler M.B.
        • Seratnahaei A.
        • Bailey A.
        • Bain J.A.
        Rhabdomyolysis precipitated by possible interaction of ticagrelor with high-dose atorvastatin.
        J Am Pharm Assoc (2003). 2015; 55: 320-323
        • van Vuren A.J.
        • de Jong B.
        • Bootsma H.P.
        • Van der Veen M.J.
        • Feith G.W.
        Ticagrelor-induced renal failure leading to statin-induced rhabdomyolysis.
        Neth J Med. 2015; 73: 136-138
        • Settergren J.
        • Eiermann B.
        • Mannheimer B.
        Adherence to drug label recommendations for avoiding drug interactions causing statin-induced myopathy–a nationwide register study.
        PLoS One. 2013; 8: e69545
        • Li D.Q.
        • Kim R.
        • McArthur E.
        • et al.
        Risk of adverse events among older adults following co-prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4.
        CMAJ. 2015; 187: 174-180
        • Ito M.K.
        • Maki K.C.
        • Brinton E.A.
        • Cohen J.D.
        • Jacobson T.A.
        Muscle symptoms in statin users, associations with cytochrome P450, and membrane transporter inhibitor use: a subanalysis of the USAGE study.
        J Clin Lipidol. 2014; 8: 69-76
        • Hung R.K.
        • Al-Mallah M.H.
        • McEvoy J.W.
        • et al.
        Prognostic value of exercise capacity in patients with coronary artery disease: the FIT (Henry Ford ExercIse Testing) project.
        Mayo Clin Proc. 2014; 89: 1644-1654
        • Hung R.K.
        • Al-Mallah M.H.
        • Qadi M.A.
        • et al.
        Cardiorespiratory fitness attenuates risk for major adverse cardiac events in hyperlipidemic men and women independent of statin therapy: the Henry Ford ExercIse Testing Project.
        Am Heart J. 2015; 170: 390-399
        • Lee D.S.
        • Markwardt S.
        • Goeres L.
        • et al.
        Statins and physical activity in older men: the osteoporotic fractures in men study.
        JAMA Intern Med. 2014; 174: 1263-1270
        • Qureshi W.T.
        • Keteyian S.J.
        • Brawner C.A.
        • et al.
        Impact of statin use on cardiorespiratory fitness in multi-racial men and women: the Henry Ford Exercise Testing (FIT) Project.
        Int J Cardiol. 2015; 197: 76-77
        • Parker B.A.
        • Capizzi J.A.
        • Grimaldi A.S.
        • et al.
        Effect of statins on skeletal muscle function.
        Circulation. 2013; 127: 96-103
        • Thompson P.D.
        • Zmuda J.M.
        • Domalik L.J.
        • et al.
        Lovastatin increases exercise-induced skeletal muscle injury.
        Metabolism. 1997; 46: 1206-1210
        • Parker B.A.
        • Augeri A.L.
        • Capizzi J.A.
        • et al.
        Effect of statins on creatine kinase levels before and after a marathon run.
        Am J Cardiol. 2012; 109: 282-287
        • Bouitbir J.
        • Daussin F.
        • Charles A.L.
        • et al.
        Mitochondria of trained skeletal muscle are protected from deleterious effects of statins.
        Muscle Nerve. 2012; 46: 367-373
        • Alis R.
        • Sanchis-Gomar F.
        • Risso-Ballester J.
        • et al.
        Inhibition of xanthine oxidase to prevent statin-induced myalgia and rhabdomiolysis.
        Atherosclerosis. 2015; 239: 38-42
        • Herrick C.
        • Bahrainy S.
        • Gill E.A.
        Statins and the liver.
        Cardiol Clin. 2015; 33: 257-265
      2. U.S. Department of Health and Human Services. U.S. Food and Drug Administration. FDA Drug Safety Communication: important safety label changes to cholesterol-lowering statin drugs. Available at: http://www.fda.gov/drugs/drugsafety/ucm293101.htm. Accessed December 8, 2015.

        • Tziomalos K.
        • Athyros V.G.
        • Paschos P.
        • Karagiannis A.
        Nonalcoholic fatty liver disease and statins.
        Metabolism. 2015; 64: 1215-1223
        • Pastori D.
        • Polimeni L.
        • Baratta F.
        • et al.
        The efficacy and safety of statins for the treatment of non-alcoholic fatty liver disease.
        Dig Liver Dis. 2015; 47: 4-11
        • Lai S.W.
        • Liao K.F.
        • Lai H.C.
        • et al.
        Statin use and risk of hepatocellular carcinoma.
        Eur J Epidemiol. 2013; 28: 485-492
        • Cash W.J.
        • O'Neill S.
        • O'Donnell M.E.
        • et al.
        Randomized controlled trial assessing the effect of simvastatin in primary biliary cirrhosis.
        Liver Int. 2013; 33: 1166-1174
        • Russo M.W.
        • Hoofnagle J.H.
        • Gu J.
        • et al.
        Spectrum of statin hepatotoxicity: experience of the drug-induced liver injury network.
        Hepatology. 2014; 60: 679-686
        • Castiella A.
        • Zapata E.
        • Lucena M.I.
        • Andrade R.J.
        Drug-induced autoimmune liver disease: a diagnostic dilemma of an increasingly reported disease.
        World J Hepatol. 2014; 6: 160-168
        • Corrao G.
        • Soranna D.
        • Casula M.
        • et al.
        High-potency statins increase the risk of acute kidney injury: evidence from a large population-based study.
        Atherosclerosis. 2014; 234: 224-229
        • Chung Y.H.
        • Lee Y.C.
        • Chang C.H.
        • et al.
        Statins of high versus low cholesterol-lowering efficacy and the development of severe renal failure.
        Pharmacoepidemiol Drug Saf. 2013; 22: 583-592
        • Layton J.B.
        • Brookhart M.A.
        • Funk M.J.
        • et al.
        Acute kidney injury in statin initiators.
        Pharmacoepidemiol Drug Saf. 2013; 22: 1061-1070
        • Geng Q.
        • Ren J.
        • Song J.
        • Li S.
        • Chen H.
        Meta-analysis of the effect of statins on renal function.
        Am J Cardiol. 2014; 114: 562-570
        • Savarese G.
        • Musella F.
        • Volpe M.
        • Paneni F.
        • Perrone-Filardi P.
        Effects of atorvastatin and rosuvastatin on renal function: a meta-analysis.
        Int J Cardiol. 2013; 167: 2482-2489
        • Wu Y.X.
        • Wang Y.
        • An C.K.
        • et al.
        Effects of rosuvastatin and atorvastatin on renal function - meta-analysis.
        Circ J. 2012; 76: 1259-1266
        • Sanguankeo A.
        • Upala S.
        • Cheungpasitporn W.
        • Ungprasert P.
        • Knight E.L.
        Effects of statins on renal outcome in chronic kidney disease patients: a systematic review and meta-analysis.
        PLoS One. 2015; 10: e0132970
        • Philips B.
        • MacPhee I.
        Do statins prevent acute kidney injury?.
        Expert Opin Drug Saf. 2015; 14: 1547-1561
        • Wong M.G.
        • Wanner C.
        • Knight J.
        • Perkovic V.
        Lowering cholesterol in chronic kidney disease: is it safe and effective?.
        Eur Heart J. 2015; 36: 2988-2995
      3. Schoenfeld SR, Lu L, Rai SK, et al. Statin use and mortality in rheumatoid arthritis: a general population-based cohort study [e-pub ahead of print]. Ann Rheum Dis http://dx.doi.org/10.1136/annrheumdis-2015–207714, accessed August 10, 2015.

        • Danninger K.
        • Hoppe U.C.
        • Pieringer H.
        Do statins reduce the cardiovascular risk in patients with rheumatoid arthritis?.
        Int J Rheum Dis. 2014; 17: 606-611
        • Myasoedova E.
        • Gabriel S.E.
        • Green A.B.
        • Matteson E.L.
        • Crowson C.S.
        Impact of statin use on lipid levels in statin-naive patients with rheumatoid arthritis versus non-rheumatoid arthritis subjects: results from a population-based study.
        Arthritis Care Res (Hoboken). 2013; 65: 1592-1599
        • Xing B.
        • Yin Y.F.
        • Zhao L.D.
        • et al.
        Effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor on disease activity in patients with rheumatoid arthritis: a meta-analysis.
        Medicine (Baltimore). 2015; 94: e572
        • Lv S.
        • Liu Y.
        • Zou Z.
        • et al.
        The impact of statins therapy on disease activity and inflammatory factor in patients with rheumatoid arthritis: a meta-analysis.
        Clin Exp Rheumatol. 2015; 33: 69-76
        • Cojocaru L.
        • Rusali A.C.
        • Suta C.
        • et al.
        The role of simvastatin in the therapeutic approach of rheumatoid arthritis.
        Autoimmune Dis. 2013; 2013: 326258
        • Villafrádez-Díaz M.
        • Santiago-Casas Y.
        • Nieves-Plaza M.
        • et al.
        Association of the use of statins with disease activity and functional status in Puerto Ricans with rheumatoid arthritis.
        P R Health Sci J. 2014; 33: 3-8
        • Kumar P.
        • Kennedy G.
        • Khan F.
        • Pullar T.
        • Belch J.J.
        Rosuvastatin might have an effect on C-reactive protein but not on rheumatoid disease activity: Tayside randomized controlled study.
        Scott Med J. 2012; 57: 80-83
        • Akiyama M.
        • Mawatari T.
        • Nakashima Y.
        • et al.
        Prevalence of dyslipidemia in Japanese patients with rheumatoid arthritis and effects of atorvastatin treatment.
        Clin Rheumatol. 2015; 34: 1867-1875
        • Pereira M.C.
        • Cardoso P.R.
        • Da Rocha Jr., L.F.
        • et al.
        Simvastatin inhibits cytokines in a dose response in patients with rheumatoid arthritis.
        Inflamm Res. 2014; 63: 309-315
        • McInnes I.B.
        • Kim H.Y.
        • Lee S.H.
        • et al.
        Open-label tofacitinib and double-blind atorvastatin in rheumatoid arthritis patients: a randomised study.
        Ann Rheum Dis. 2014; 73: 124-131
        • Mazilu D.
        • Gudu T.
        • Ionescu R.
        • Opris D.
        Statins do not influence long-term rituximab clinical efficiency in rheumatoid arthritis patients.
        Biomed Res Int. 2014; 2014: 689426
        • Schmidt T.
        • Battafarano D.F.
        • Mortensen E.M.
        • Frei C.R.
        • Mansi I.
        Frequency of development of connective tissue disease in statin-users versus nonusers.
        Am J Cardiol. 2013; 112: 883-888
        • Ruiz-Limon P.
        • Barbarroja N.
        • Perez-Sanchez C.
        • et al.
        Atherosclerosis and cardiovascular disease in systemic lupus erythematosus: effects of in vivo statin treatment.
        Ann Rheum Dis. 2015; 74: 1450-1458
        • Fatemi A.
        • Moosavi M.
        • Sayedbonakdar Z.
        • et al.
        Atorvastatin effect on systemic lupus erythematosus disease activity: a double-blind randomized clinical trial.
        Clin Rheumatol. 2014; 33: 1273-1278
        • Khattri S.
        • Zandman-Goddard G.
        Statins and autoimmunity.
        Immunol Res. 2013; 56: 348-357
        • Schmidt J.
        • Kermani T.A.
        • Muratore F.
        • et al.
        Statin use in giant cell arteritis: a retrospective study.
        J Rheumatol. 2013; 40: 910-915
        • Tremoulet A.H.
        The role of statins in inflammatory vasculitides.
        Autoimmunity. 2015; 48: 177-180
        • Sen D.
        • Rosenstein E.D.
        • Kramer N.
        ANCA-positive vasculitis associated with simvastatin/ezetimibe: expanding the spectrum of statin-induced autoimmunity?.
        Int J Rheum Dis. 2010; 13: e29-e31
        • de Munter W.
        • van der Kraan P.M.
        • van den Berg W.B.
        • van Lent P.L.
        High systemic levels of low-density lipoprotein cholesterol: fuel to the flames in inflammatory osteoarthritis?.
        Rheumatology (Oxford). 2016; 55: 16-24
        • Kadam U.T.
        • Blagojevic M.
        • Belcher J.
        Statin use and clinical osteoarthritis in the general population: a longitudinal study.
        J Gen Intern Med. 2013; 28: 943-949
        • Clockaerts S.
        • Van Osch G.J.
        • Bastiaansen-Jenniskens Y.M.
        • et al.
        Statin use is associated with reduced incidence and progression of knee osteoarthritis in the Rotterdam study.
        Ann Rheum Dis. 2012; 71: 642-647
        • deLemos A.S.
        • Foureau D.M.
        • Jacobs C.
        • et al.
        Drug-induced liver injury with autoimmune features.
        Semin Liver Dis. 2014; 34: 194-204
        • Kim S.Y.
        • Kim S.J.
        • Yoon D.
        • et al.
        A case of statin-induced interstitial pneumonitis due to rosuvastatin.
        Tuberc Respir Dis (Seoul). 2015; 78: 281-285
        • Huang L.K.
        • Tsai M.J.
        • Tsai H.C.
        • et al.
        Statin-induced lung injury: diagnostic clue and outcome.
        Postgrad Med J. 2013; 89: 14-19
        • Gale J.
        • Danesh-Meyer H.V.
        Statins can induce myasthenia gravis.
        J Clin Neurosci. 2014; 21: 195-197
      4. Gonen KA, Erfan G, Oznur M, Erdogan C. The first case of Henoch-Schonlein purpura associated with rosuvastatin: colonic involvement coexisting with small intestine [e-pub ahead of print]. BMJ Case Rep http://dx.doi.org/10.1136/bcr-2013–202644, accessed March 27, 2014.

        • Komai E.
        • Takemoto M.
        • Yokote K.
        Atorvastatin-induced dermatomyositis in a 47-year-old woman with Sjogren's syndrome.
        Acta Cardiol. 2015; 70: 373
        • Kirchgesner T.
        • Larbi A.
        • Omoumi P.
        • et al.
        Drug-induced tendinopathy: from physiology to clinical applications.
        Joint Bone Spine. 2014; 81: 485-492
        • Hamdi W.
        • Ghannouchi M.M.
        • Kaffel D.
        • Kchir M.M.
        Piriformis muscle syndrome: an unusual adverse effect of atorvastatin.
        J Clin Rheumatol. 2013; 19: 156-157
        • Thai M.
        • Hilmer S.
        • Pearson S.A.
        • Reeve E.
        • Gnjidic D.
        Prevalence of potential and clinically relevant statin-drug interactions in frail and robust older inpatients.
        Drugs Aging. 2015; 32: 849-856
        • Afilalo J.
        • Duque G.
        • Steele R.
        • et al.
        Statins for secondary prevention in elderly patients: a hierarchical bayesian meta-analysis.
        J Am Coll Cardiol. 2008; 51: 37-45
        • Yan Y.L.
        • Qiu B.
        • Hu L.J.
        • et al.
        Efficacy and safety evaluation of intensive statin therapy in older patients with coronary heart disease: a systematic review and meta-analysis.
        Eur J Clin Pharmacol. 2013; 69: 2001-2009
        • LaRosa J.C.
        Treatment of cholesterol in the elderly: statins and beyond.
        Curr Atheroscler Rep. 2014; 16: 385
        • Iwere R.B.
        • Hewitt J.
        Myopathy in older people receiving statin therapy: a systematic review and meta-analysis.
        Br J Clin Pharmacol. 2015; 80: 363-371
        • Teng M.
        • Lin L.
        • Zhao Y.J.
        • et al.
        Statins for primary prevention of cardiovascular disease in elderly patients: systematic review and meta-analysis.
        Drugs Aging. 2015; 32: 649-661
        • Kutner J.S.
        • Blatchford P.J.
        • Taylor Jr., D.H.
        • et al.
        Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial.
        JAMA Intern Med. 2015; 175: 691-700
        • Panayiotou G.
        • Paschalis V.
        • Nikolaidis M.G.
        • et al.
        No adverse effects of statins on muscle function and health-related parameters in the elderly: an exercise study.
        Scand J Med Sci Sports. 2013; 23: 556-567
        • Steenland K.
        • Zhao L.
        • Goldstein F.C.
        • Levey A.I.
        Statins and cognitive decline in older adults with normal cognition or mild cognitive impairment.
        J Am Geriatr Soc. 2013; 61: 1449-1455
        • Wu C.K.
        • Yang Y.H.
        • Lin T.T.
        • et al.
        Statin use reduces the risk of dementia in elderly patients: a nationwide data survey and propensity analysis.
        J Intern Med. 2015; 277: 343-352
        • Manocha D.
        • Bansal N.
        • Gumaste P.
        • Brangman S.
        Safety profile of high-dose statin therapy in geriatric patients with stroke.
        South Med J. 2013; 106: 658-664
        • Hilmer S.
        • Gnjidic D.
        Statins in older adults.
        Aust Prescr. 2013; 36: 79-82
        • Gnjidic D.
        • Naganathan V.
        • Freedman S.B.
        • et al.
        Statin therapy and cognition in older people: what is the evidence?.
        Curr Clin Pharmacol. 2015; 10: 185-193
        • Iso H.
        • Jacobs Jr., D.R.
        • Wentworth D.
        • Neaton J.D.
        • Cohen J.D.
        Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the multiple risk factor intervention trial.
        N Engl J Med. 1989; 320: 904-910
        • Goldstein L.B.
        • Amarenco P.
        • Szarek M.
        • et al.
        Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study.
        Neurology. 2008; 70: 2364-2370
        • Hackam D.G.
        • Woodward M.
        • Newby L.K.
        • et al.
        Statins and intracerebral hemorrhage collaborative systematic review and meta-analysis.
        Circulation. 2011; 124: 2233-2242
        • McKinney J.S.
        • Kostis W.J.
        Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials.
        Stroke. 2012; 43: 2149-2156
        • Wang W.
        • Zhang B.
        Statins for the prevention of stroke: a meta-analysis of randomized controlled trials.
        PLoS One. 2014; 9: e92388
        • Salmoirago-Blotcher E.
        • Hovey K.M.
        • Andrews C.A.
        • et al.
        Statin use and risk of haemorrhagic stroke in a community-based cohort of postmenopausal women: an observational study from the Women's Health Initiative.
        BMJ Open. 2015; 5: e007075
        • Lei C.
        • Wu B.
        • Liu M.
        • Chen Y.
        Association between statin use and intracerebral hemorrhage: a systematic review and meta-analysis.
        Eur J Neurol. 2014; 21: 192-198
        • Kirkpatrick P.J.
        • Turner C.L.
        • Smith C.
        • et al.
        Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): a multicentre randomised phase 3 trial.
        Lancet Neurol. 2014; 13: 666-675
        • Wong G.K.
        • Wong A.
        • Zee B.C.
        • et al.
        Cognitive outcome in acute simvastatin treatment for aneurysmal subarachnoid hemorrhage: a propensity matched analysis.
        J Neurol Sci. 2015; 358: 58-61
        • Jung J.M.
        • Choi J.Y.
        • Kim H.J.
        • Seo W.K.
        Statin use in spontaneous intracerebral hemorrhage: a systematic review and meta-analysis.
        Int J Stroke. 2015; 10: 10-17
        • Tapia Perez J.H.
        • Yildiz O.C.
        • Schneider T.
        • Nimsky C.
        Meta-analysis of statin use for the acute therapy of spontaneous intracerebral hemorrhage.
        J Stroke Cerebrovasc Dis. 2015; 24: 2521-2526
        • Guo J.
        • Li J.
        • Zhou M.
        • et al.
        Statin treatment reduces the risk of poststroke seizures.
        Neurology. 2015; 85: 701-707
        • Siniscalchi A.
        • Mintzer S.
        Statins for poststroke seizures: the first antiepileptogenic agent?.
        Neurology. 2015; 85: 661-662
        • Kotlęga D.
        • Gołąb-Janowska M.
        • Masztalewicz M.
        • Ciećwież S.
        • Nowacki P.
        Potential role of statins in the intracerebral hemorrhage and subarachnoid hemorrhage.
        Neurol Neurochir Pol. 2015; 49: 322-328
        • Edison R.J.
        • Muenke M.
        Central nervous system and limb anomalies in case reports of first-trimester statin exposure.
        N Engl J Med. 2004; 350: 1579-1582
        • Bateman B.T.
        • Hernandez-Diaz S.
        • Fischer M.A.
        • et al.
        Statins and congenital malformations: cohort study.
        BMJ. 2015; 350: h1035
        • Lecarpentier E.
        • Morel O.
        • Fournier T.
        • et al.
        Statins and pregnancy: between supposed risks and theoretical benefits.
        Drugs. 2012; 72: 773-788
        • Morton S.
        • Thangaratinam S.
        Statins in pregnancy.
        Curr Opin Obstet Gynecol. 2013; 25: 433-440
        • Winterfeld U.
        • Allignol A.
        • Panchaud A.
        • et al.
        Pregnancy outcome following maternal exposure to statins: a multicentre prospective study.
        BJOG. 2013; 120: 463-471
        • Schutte A.E.
        • Symington E.A.
        • du Preez J.L.
        Rosuvastatin is transferred into human breast milk: a case report.
        Am J Med. 2013; 126: E7-E8
        • McCrindle B.W.
        Familial hypercholesterolemia in children and adolescents.
        Curr Opin Lipidol. 2012; 23: 525-531
        • Genest J.
        • Hegele R.A.
        • Bergeron J.
        • et al.
        Canadian Cardiovascular Society position statement on familial hypercholesterolemia.
        Can J Cardiol. 2014; 30: 1471-1481
        • Nordestgaard B.G.
        • Chapman M.J.
        • Humphries S.E.
        • et al.
        Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease.
        Eur Heart J. 2013; 34: 3478-3490
        • Luirink I.K.
        • Hutten B.A.
        • Wiegman A.
        Optimizing treatment of familial hypercholesterolemia in children and adolescents.
        Curr Cardiol Rep. 2015; 17: 629
        • Miller M.L.
        • Wright C.C.
        • Browne B.
        Lipid-lowering medications for children and adolescents.
        J Clin Lipidol. 2015; 9: S67-S76
        • Kusters D.M.
        • Avis H.J.
        • de Groot E.
        • et al.
        Ten-year follow-up after initiation of statin therapy in children with familial hypercholesterolemia.
        JAMA. 2014; 312: 1055-1057
        • Braamskamp M.J.
        • Kusters D.M.
        • Avis H.J.
        • et al.
        Long-term statin treatment in children with familial hypercholesterolemia: more insight into tolerability and adherence.
        Paediatr Drugs. 2015; 17: 159-166
      5. CardioRisk Calculator. Available at: http://www.circl.ubc.ca/cardiorisk-calculator.html. Accessed December 8, 2015.

        • Joy T.R.
        • Monjed A.
        • Zou G.Y.
        • et al.
        N-of-1 (single-patient) trials for statin-related myalgia.
        Ann Intern Med. 2014; 160: 301-310
        • Zhang H.
        • Plutzky J.
        • Skentzos S.
        • et al.
        Discontinuation of statins in routine care settings: a cohort study.
        Ann Intern Med. 2013; 158: 526-534
        • Mampuya W.M.
        • Frid D.
        • Rocco M.
        • et al.
        Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience.
        Am Heart J. 2013; 166: 597-603
        • Christopher-Stine L.
        • Casciola-Rosen L.A.
        • Hong G.
        • et al.
        A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy.
        Arthritis Rheum. 2010; 62: 2757-2766
        • Metterlein T.
        • Schuster F.
        • Tadda L.
        • et al.
        Statins alter intracellular calcium homeostasis in malignant hyperthermia susceptible individuals.
        Cardiovasc Ther. 2010; 28: 356-360
        • Knoblauch M.
        • Dagnino-Acosta A.
        • Hamilton S.L.
        Mice with RyR1 mutation (Y524S) undergo hypermetabolic response to simvastatin.
        Skelet Muscle. 2013; 3: 22
        • Guis S.
        • Bendahan D.
        • Kozak-Ribbens G.
        • et al.
        Rhabdomyolysis and myalgia associated with anticholesterolemic treatment as potential signs of malignant hyperthermia susceptibility.
        Arthritis Rheum. 2003; 49: 237-238
        • Guis S.
        • Figarella-Branger D.
        • Mattei J.P.
        • et al.
        In vivo and in vitro characterization of skeletal muscle metabolism in patients with statin-induced adverse effects.
        Arthritis Rheum. 2006; 55: 551-557
        • Hedenmalm K.
        • Granberg A.G.
        • Dahl M.L.
        Statin-induced muscle toxicity and susceptibility to malignant hyperthermia and other muscle diseases: a population-based case-control study including 1st and 2nd degree relatives.
        Eur J Clin Pharmacol. 2015; 71: 117-124
        • Kley R.A.
        • Tarnopolsky M.A.
        • Vorgerd M.
        Creatine for treating muscle disorders.
        Cochrane Database Syst Rev. 2013; : CD004760
        • Mareedu R.K.
        • Modhia F.M.
        • Kanin E.I.
        • et al.
        Use of an electronic medical record to characterize cases of intermediate statin-induced muscle toxicity.
        Prev Cardiol. 2009; 12: 88-94
        • Carr D.F.
        • Alfirevic A.
        • Johnson R.
        • et al.
        GATM gene variants and statin myopathy risk.
        Nature. 2014; 513: E1
        • Nouioua S.
        • Cheillan D.
        • Zaouidi S.
        • et al.
        Creatine deficiency syndrome. A treatable myopathy due to arginine-glycine amidinotransferase (AGAT) deficiency.
        Neuromuscul Disord. 2013; 23: 670-674
        • Rando L.P.
        • Cording S.A.
        • Newnham H.H.
        Successful reintroduction of statin therapy after myositis: was there another cause?.
        Med J Aust. 2004; 180: 472-473
        • Simons J.E.
        • Holbrook A.M.
        • Don-Wauchope A.C.
        Successful reintroduction of statin therapy after statin-associated rhabdomyolysis.
        J Clin Lipidol. 2015; 9: 594-596
        • Schirris T.J.
        • Renkema G.H.
        • Ritschel T.
        • et al.
        Statin-induced myopathy is associated with mitochondrial complex III inhibition.
        Cell Metab. 2015; 22: 399-407
        • Trapani L.
        • Segatto M.
        • La Rosa P.
        • et al.
        3-Hydroxy 3-methylglutaryl coenzyme A reductase inhibition impairs muscle regeneration.
        J Cell Biochem. 2012; 113: 2057-2063
        • Peric D.
        • Barragan I.
        • Giraud-Triboult K.
        • et al.
        Cytostatic effect of repeated exposure to simvastatin: a mechanism for chronic myotoxicity revealed by the use of mesodermal progenitors derived from human pluripotent stem cells.
        Stem Cells. 2015; 33: 2936-2948
        • Bhandari S.
        • Gupta P.
        • Quinn P.
        • et al.
        Pleiotropic effects of statins in hypercholesterolaemia: a prospective observational study using a lipoproteomic based approach.
        Lancet. 2015; 385: S21
        • Singh P.
        • Saxena R.
        • Srinivas G.
        • Pande G.
        • Chattopadhyay A.
        Cholesterol biosynthesis and homeostasis in regulation of the cell cycle.
        PLoS One. 2013; 8: e58833
        • Singh F.
        • Charles A.L.
        • Schlagowski A.I.
        • et al.
        Reductive stress impairs myoblasts mitochondrial function and triggers mitochondrial hormesis.
        Biochim Biophys Acta. 2015; 1853: 1574-1585
        • Giordano N.
        • Senesi M.
        • Mattii G.
        • et al.
        Polymyositis associated with simvastatin.
        Lancet. 1997; 349: 1600-1601
        • Noel B.
        • Cerottini J.P.
        • Panizzon R.G.
        Atorvastatin-induced dermatomyositis.
        Am J Med. 2001; 110: 670-671
        • Hoogendijk J.E.
        • Amato A.A.
        • Lecky B.R.
        • et al.
        119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10-12 October 2003.
        14. Neuromuscul Disord, Naarden, The Netherlands2004: 337-345
        • McKelvie P.A.
        • Dennett X.
        Myopathy associated with HMG-CoA reductase inhibitors (statins): a series of 10 patients and review of the literature.
        J Clin Neuromuscul Dis. 2002; 3: 143-148
        • Grable-Esposito P.
        • Katzberg H.D.
        • Greenberg S.A.
        • et al.
        Immune-mediated necrotizing myopathy associated with statins.
        Muscle Nerve. 2010; 41: 185-190
        • Mammen A.L.
        • Chung T.
        • Christopher-Stine L.
        • et al.
        Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy.
        Arthritis Rheum. 2011; 63: 713-721
        • Werner J.L.
        • Christopher-Stine L.
        • Ghazarian S.R.
        • et al.
        Antibody levels correlate with creatine kinase levels and strength in anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy.
        Arthritis Rheum. 2012; 64: 4087-4093
        • Mammen A.L.
        • Gaudet D.
        • Brisson D.
        • et al.
        Increased frequency of DRB1*11:01 in anti-hydroxymethylglutaryl-coenzyme A reductase-associated autoimmune myopathy.
        Arthritis Care Res (Hoboken). 2012; 64: 1233-1237
      6. Satoh M, Tanaka S, Ceribelli A, Calise SJ, Chan EK. A comprehensive overview on myositis-specific antibodies: new and old biomarkers in idiopathic inflammatory myopathy [e-pub ahead of print]. Clin Rev Allergy Immunol http://dx.doi.org/10.1007/s12016-015-8510-y, accessed October 2, 2015.

        • Mohassel P.
        • Mammen A.L.
        Statin-associated autoimmune myopathy and anti-HMGCR autoantibodies.
        Muscle Nerve. 2013; 48: 477-483
        • Allenbach Y.
        • Drouot L.
        • Rigolet A.
        • et al.
        Anti-HMGCR autoantibodies in European patients with autoimmune necrotizing myopathies: inconstant exposure to statin.
        Medicine (Baltimore). 2014; 93: 150-157
      7. Kassardjian CD, Lennon VA, Alfugham NB, Mahler M, Milone M. Clinical Features and Treatment Outcomes of Necrotizing Autoimmune Myopathy. JAMA Neurol 2015;72:996-1003.

      8. Watanabe Y, Suzuki S, Nishimura H, et al. Statins and myotoxic effects associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: an observational study in Japan. Medicine (Baltimore)2015;94:e416.

        • Klein M.
        • Mann H.
        • Plestilova L.
        • et al.
        Increasing incidence of immune-mediated necrotizing myopathy: single-centre experience.
        Rheumatology (Oxford). 2015; 54: 2010-2014
        • Chen Z.
        • Hu W.
        • Wang Y.
        • et al.
        Distinct profiles of myositis-specific autoantibodies in Chinese and Japanese patients with polymyositis/dermatomyositis.
        Clin Rheumatol. 2015; 34: 1627-1631
        • Wu Y.
        • Lach B.
        • Provias J.P.
        • Tarnopolsky M.A.
        • Baker S.K.
        Statin-associated autoimmune myopathies: a pathophysiologic spectrum.
        Can J Neurol Sci. 2014; 41: 638-647
        • Albayda J.
        • Christopher-Stine L.
        Identifying statin-associated autoimmune necrotizing myopathy.
        Cleve Clin J Med. 2014; 81: 736-741
        • Limaye V.
        • Bundell C.
        • Hollingsworth P.
        • et al.
        Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase in patients with immune-mediated myositis and necrotizing myopathy.
        Muscle Nerve. 2015; 52: 196-203
        • Lahaye C.
        • Beaufrere A.M.
        • Boyer O.
        • et al.
        Immune-mediated myopathy related to anti 3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies as an emerging cause of necrotizing myopathy induced by statins.
        Joint Bone Spine. 2014; 81: 79-82
        • Fernandes G.H.
        • Zanoteli E.
        • Shinjo S.K.
        Statin-associated necrotizing autoimmune myopathy.
        Mod Rheumatol. 2014; 24: 862-864
        • Casciola-Rosen L.
        • Mammen A.L.
        Myositis autoantibodies.
        Curr Opin Rheumatol. 2012; 24: 602-608
        • Charles-Schoeman C.
        • Amjadi S.S.
        • Paulus H.E.
        Treatment of dyslipidemia in idiopathic inflammatory myositis: results of the International Myositis Assessment and Clinical Studies Group survey.
        Clin Rheumatol. 2012; 31: 1163-1168
        • Sancricca C.
        • Mora M.
        • Ricci E.
        • et al.
        Pilot trial of simvastatin in the treatment of sporadic inclusion-body myositis.
        Neurol Sci. 2011; 32: 841-847
        • Kyriakides T.
        • Angelini C.
        • Schaefer J.
        • et al.
        EFNS review on the role of muscle biopsy in the investigation of myalgia.
        Eur J Neurol. 2013; 20: 997-1005
        • Joosten H.
        • Visser S.T.
        • van Eersel M.E.
        • et al.
        Statin use and cognitive function: population-based observational study with long-term follow-up.
        PLoS One. 2014; 9: e115755
        • Chitnis A.S.
        • Aparasu R.R.
        • Chen H.
        • et al.
        Use of statins and risk of dementia in heart failure: a retrospective cohort study.
        Drugs Aging. 2015; 32: 743-754
        • Jamolowicz A.I.
        • Chen H.Y.
        • Panegyres P.K.
        Statins and memory loss: an Australian experience.
        Australas Med J. 2015; 8: 73-79
        • Chen J.M.
        • Chang C.W.
        • Chang T.H.
        • et al.
        Effects of statins on incident dementia in patients with type 2 DM: a population-based retrospective cohort study in Taiwan.
        PLoS One. 2014; 9: e88434
        • Corrao G.
        • Ibrahim B.
        • Nicotra F.
        • et al.
        Long-term use of statins reduces the risk of hospitalization for dementia.
        Atherosclerosis. 2013; 230: 171-176
        • Douiri A.
        • McKevitt C.
        • Emmett E.S.
        • Rudd A.G.
        • Wolfe C.D.
        Long-term effects of secondary prevention on cognitive function in stroke patients.
        Circulation. 2013; 128: 1341-1348
        • Wong W.B.
        • Lin V.W.
        • Boudreau D.
        • Devine E.B.
        Statins in the prevention of dementia and Alzheimer's disease: a meta-analysis of observational studies and an assessment of confounding.
        Pharmacoepidemiol Drug Saf. 2013; 22: 345-358
        • Chen P.Y.
        • Liu S.K.
        • Chen C.L.
        • Wu C.S.
        Long-term statin use and dementia risk in Taiwan.
        J Geriatr Psychiatry Neurol. 2014; 27: 165-171
        • Chou C.Y.
        • Chou Y.C.
        • Chou Y.J.
        • Yang Y.F.
        • Huang N.
        Statin use and incident dementia: a nationwide cohort study of Taiwan.
        Int J Cardiol. 2014; 173: 305-310
        • Chuang C.S.
        • Lin C.L.
        • Lin M.C.
        • Sung F.C.
        • Kao C.H.
        Decreased prevalence of dementia associated with statins: a national population-based study.
        Eur J Neurol. 2015; 22: 912-918
        • Chao T.F.
        • Liu C.J.
        • Chen S.J.
        • et al.
        Statins and the risk of dementia in patients with atrial fibrillation: a nationwide population-based cohort study.
        Int J Cardiol. 2015; 196: 91-97
        • Nadkarni N.K.
        • Perera S.
        • Hanlon J.T.
        • et al.
        Statins and brain integrity in older adults: secondary analysis of the Health ABC study.
        Alzheimers Dement. 2015; 11: 1202-1211
        • Xiong Y.
        • Wong A.
        • Cavalieri M.
        • et al.
        Prestroke statins, progression of white matter hyperintensities, and cognitive decline in stroke patients with confluent white matter hyperintensities.
        Neurotherapeutics. 2014; 11: 606-611
        • Yang Y.H.
        • Teng H.W.
        • Lai Y.T.
        • et al.
        Statins reduces the risk of dementia in patients with late-onset depression: a retrospective cohort study.
        PLoS One. 2015; 10: e0137914
        • McGuinness B.
        • O'Hare J.
        • Craig D.
        • et al.
        Statins for the treatment of dementia.
        Cochrane Database Syst Rev. 2010; : CD007514
        • Richardson K.
        • Schoen M.
        • French B.
        • et al.
        Statins and cognitive function: a systematic review.
        Ann Intern Med. 2013; 159: 688-697
        • Swiger K.J.
        • Manalac R.J.
        • Blumenthal R.S.
        • Blaha M.J.
        • Martin S.S.
        Statins and cognition: a systematic review and meta-analysis of short- and long-term cognitive effects.
        Mayo Clin Proc. 2013; 88: 1213-1221
        • Hendrie H.C.
        • Hake A.
        • Lane K.
        • et al.
        Statin use, incident dementia and Alzheimer disease in elderly African Americans.
        Ethn Dis. 2015; 25: 345-354
        • Liang T.
        • Li R.
        • Cheng O.
        Statins for treating Alzheimer's disease: truly ineffective?.
        Eur Neurol. 2015; 73: 360-366
        • Ott B.R.
        • Daiello L.A.
        • Dahabreh I.J.
        • et al.
        Do statins impair cognition? A systematic review and meta-analysis of randomized controlled trials.
        J Gen Intern Med. 2015; 30: 348-358
        • Power M.C.
        • Weuve J.
        • Sharrett A.R.
        • Blacker D.
        • Gottesman R.F.
        Statins, cognition, and dementia-systematic review and methodological commentary.
        Nat Rev Neurol. 2015; 11: 220-229
        • Ancelin M.L.
        • Carrière I.
        • Barberger-Gateau P.
        • et al.
        Lipid lowering agents, cognitive decline, and dementia: the Three-City Study.
        J Alzheimers Dis. 2012; 30: 629-637
        • Strom B.L.
        • Schinnar R.
        • Karlawish J.
        • et al.
        Statin therapy and risk of acute memory impairment.
        JAMA Intern Med. 2015; 175: 1399-1405
        • Daneschvar H.L.
        • Aronson M.D.
        • Smetana G.W.
        Do statins prevent Alzheimer's disease? A narrative review.
        Eur J Intern Med. 2015; 26: 666-669
        • Fathallah N.
        • Slim R.
        • Larif S.
        • Hmouda H.
        Ben Salem C. Drug-induced hyperglycaemia and diabetes.
        Drug Saf. 2015; 38: 1153-1168
        • Sattar N.
        • Preiss D.
        • Murray H.M.
        • et al.
        Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials.
        Lancet. 2010; 375: 735-742
        • Preiss D.
        • Seshasai S.R.
        • Welsh P.
        • et al.
        Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis.
        JAMA. 2011; 305: 2556-2564
        • Chen C.W.
        • Chen T.C.
        • Huang K.Y.
        • et al.
        Differential impact of statin on new-onset diabetes in different age groups: a population-based case-control study in women from an asian country.
        PLoS One. 2013; 8: e71817
        • Danaei G.
        • García Rodríguez L.A.
        • Fernandez Cantero O.
        • Hernán M.A.
        Statins and risk of diabetes: an analysis of electronic medical records to evaluate possible bias due to differential survival.
        Diabetes Care. 2013; 36: 1236-1240
        • 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. 2012; 380: 565-571
        • Waters D.D.
        • Ho J.E.
        • Boekholdt S.M.
        • et al.
        Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy effect of baseline risk factors for diabetes.
        J Am Coll Cardiol. 2013; 61: 148-152
        • Fuentes F.
        • Alcala-Diaz J.F.
        • Watts G.F.
        • et al.
        Statins do not increase the risk of developing type 2 diabetes in familial hypercholesterolemia: the SAFEHEART study.
        Int J Cardiol. 2015; 201: 79-84
        • Kohli P.
        • Waters D.D.
        • Nemr R.
        • et al.
        Risk of new-onset diabetes and cardiovascular risk reduction from high-dose statin therapy in pre-diabetics and non-pre-diabetics: an analysis from TNT and IDEAL.
        J Am Coll Cardiol. 2015; 65: 402-404
        • Mansi I.
        • Frei C.R.
        • Wang C.P.
        • Mortensen E.M.
        Statins and new-onset diabetes mellitus and diabetic complications: a retrospective cohort study of US healthy adults.
        J Gen Intern Med. 2015; 30: 1599-1610
        • Fulcher J.
        • O'Connell R.
        • et al.
        • Cholesterol Treatment Trialists Collaboration
        Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials.
        Lancet. 2015; 385: 1397-1405
        • Erqou S.
        • Lee C.
        • Adler A.
        Statins and glycaemic control in individuals with diabetes: a systematic review and meta-analysis.
        Diabetologia. 2014; 57: 2444-2452
        • Brahm A.J.
        • Hegele R.A.
        Incident diabetes with statins: biology, artifact, or both?.
        Can J Cardiol. 2015; 31: 963-965
        • Birnbaum Y.
        • Nanhwan M.K.
        • Ling S.
        • et al.
        PTEN upregulation may explain the development of insulin resistance and type 2 diabetes with high dose statins.
        Cardiovasc Drugs Ther. 2014; 28: 447-457
        • Swerdlow D.I.
        • Sattar N.
        A dysglycaemic effect of statins in diabetes: relevance to clinical practice?.
        Diabetologia. 2014; 57: 2433-2435
        • Besseling J.
        • Kastelein J.J.
        • Defesche J.C.
        • Hutten B.A.
        • Hovingh G.K.
        Association between familial hypercholesterolemia and prevalence of type 2 diabetes mellitus.
        JAMA. 2015; 313: 1029-1036
        • Frayling T.M.
        Statins and type 2 diabetes: genetic studies on target.
        Lancet. 2015; 385: 310-312
        • Gotoh S.
        • Negishi M.
        Statin-activated nuclear receptor PXR promotes SGK2 dephosphorylation by scaffolding PP2C to induce hepatic gluconeogenesis.
        Sci Rep. 2015; 5: 14076
        • Wang H.J.
        • Park J.Y.
        • Kwon O.
        • et al.
        Chronic HMGCR/HMG-CoA reductase inhibitor treatment contributes to dysglycemia by upregulating hepatic gluconeogenesis through autophagy induction.
        Autophagy. 2015; 11: 2089-2101
        • Wang K.L.
        • Liu C.J.
        • Chao T.F.
        • et al.
        Risk of new-onset diabetes mellitus versus reduction in cardiovascular events with statin therapy.
        Am J Cardiol. 2014; 113: 631-636
        • Furuya-Kanamori L.
        • Stone J.C.
        • Doi S.A.
        Putting the diabetes risk due to statins in perspective: a re-evaluation using the complementary outcome.
        Nutr Metab Cardiovasc Dis. 2014; 24: 705-708
        • Bernardi A.
        • Rocha V.Z.
        • Faria-Neto J.R.
        Use of statins and the incidence of type 2 diabetes mellitus.
        Rev Assoc Med Bras. 2015; 61: 375-380
      9. Fernandes R, Shaikh I, Wegstapel H. Possible association between statin use and bowel dysmotility. BMJ Case Rep 2012: bcr1020114918.

        • Cortes-Bergoderi M.
        • Pineda A.M.
        • Santana O.
        The pleiotropic effects and therapeutic potential of the hydroxy-methyl-glutaryl-CoA reductase inhibitors in gastrointestinal tract disorders: a comprehensive review.
        J Gastrointestin Liver Dis. 2013; 22: 199-204
        • Tokinaga K.
        • Oeda T.
        • Suzuki Y.
        • Matsushima Y.
        HMG-CoA reductase inhibitors (statins) might cause high elevations of creatine phosphokinase (CK) in patients with unnoticed hypothyroidism.
        Endocr J. 2006; 53: 401-405
        • Chaudhary N.
        • Duggal A.K.
        • Makhija P.
        • Puri V.
        • Khwaja G.A.
        Statin-induced bilateral foot drop in a case of hypothyroidism.
        Ann Indian Acad Neurol. 2015; 18: 331-334
        • Robison C.D.
        • Bair T.L.
        • Horne B.D.
        • et al.
        Hypothyroidism as a risk factor for statin intolerance.
        J Clin Lipidol. 2014; 8: 401-407
        • Kiernan T.J.
        • Rochford M.
        • McDermott J.H.
        Simvastatin induced rhabdomyolysis and an important clinical link with hypothyroidism.
        Int J Cardiol. 2007; 119: 374-376
        • Kisch E.
        • Segall H.S.
        Interaction between simvastatin and L-thyroxine.
        Ann Intern Med. 2005; 143: 547
        • Hung S.H.
        • Lin H.C.
        • Chung S.D.
        Statin use and thyroid cancer: a population-based case-control study.
        Clin Endocrinol (Oxf). 2015; 83: 111-116
        • Parsons J.K.
        Modifiable risk factors for benign prostatic hyperplasia and lower urinary tract symptoms: new approaches to old problems.
        J Urol. 2007; 178: 395-401
        • Rees R.W.
        • Foxwell N.A.
        • Ralph D.J.
        • et al.
        Y-27632 a Rho-kinase inhibitor, inhibits proliferation and adrenergic contraction of prostatic smooth muscle cells.
        J Urol. 2003; 170: 2517-2522
        • Watts K.L.
        • Spiteri M.A.
        Connective tissue growth factor expression and induction by transforming growth factor-beta is abrogated by simvastatin via a Rho signaling mechanism.
        Am J Physiol Lung Cell Mol Physiol. 2004; 287: L1323-L1332
        • Padayatty S.J.
        • Marcelli M.
        • Shao T.C.
        • Cunningham G.R.
        Lovastatin-induced apoptosis in prostate stromal cells.
        J Clin Endocrinol Metab. 1997; 82: 1434-1439
        • Sivaprasad U.
        • Abbas T.
        • Dutta A.
        Differential efficacy of 3-hydroxy-3-methylglutaryl CoA reductase inhibitors on the cell cycle of prostate cancer cells.
        Mol Cancer Ther. 2006; 5: 2310-2316
        • Lee S.H.
        • Park T.J.
        • Bae M.H.
        • et al.
        Impact of treatment with statins on prostate-specific antigen and prostate volume in patients with benign prostatic hyperplasia.
        Korean J Urol. 2013; 54: 750-755
        • Mondul A.M.
        • Giovannucci E.
        • Platz E.A.
        A prospective study of statin drug use and lower urinary tract symptoms in older men.
        Am J Epidemiol. 2013; 178: 797-803
        • Fujimoto M.
        • Higuchi T.
        • Hosomi K.
        • Takada M.
        Association of statin use with storage lower urinary tract symptoms (LUTS): data mining of prescription database.
        Int J Clin Pharmacol Ther. 2014; 52: 762-769
        • Fujimoto M.
        • Hosomi K.
        • Takada M.
        Statin-associated lower urinary tract symptoms: data mining of the public version of the FDA adverse event reporting system, FAERS.
        Int J Clin Pharmacol Ther. 2014; 52: 259-266
        • Huang C.Y.
        • Chung S.D.
        • Kao L.T.
        • Lin H.C.
        • Wang L.H.
        Statin use is associated with bladder pain syndrome/interstitial cystitis: a population-based case-control study.
        Urol Int. 2015; 95: 227-232
        • Goldstein J.L.
        • Brown M.S.
        Regulation of the mevalonate pathway.
        Nature. 1990; 343: 425-430
        • Ali S.K.
        • Reveles K.R.
        • Davis R.
        • et al.
        The association of statin use and gonado-sexual function in women: a retrospective cohort analysis.
        J Sex Med. 2015; 12: 83-92
        • Davis R.
        • Reveles K.R.
        • Ali S.K.
        • et al.
        Statins and male sexual health: a retrospective cohort analysis.
        J Sex Med. 2015; 12: 158-167
        • Chou C.Y.
        • Yang Y.F.
        • Chou Y.J.
        • Hu H.Y.
        • Huang N.
        Statin use and incident erectile dysfunction - a nationwide propensity-matched cohort study in Taiwan.
        Int J Cardiol. 2015; 202: 883-888
        • Dobs A.S.
        • Schrott H.
        • Davidson M.H.
        • et al.
        Effects of high-dose simvastatin on adrenal and gonadal steroidogenesis in men with hypercholesterolemia.
        Metabolism. 2000; 49: 1234-1238
        • Cai X.
        • Tian Y.
        • Wu T.
        • et al.
        The role of statins in erectile dysfunction: a systematic review and meta-analysis.
        Asian J Androl. 2014; 16: 461-466
        • Cui Y.
        • Zong H.
        • Yan H.
        • Zhang Y.
        The effect of statins on erectile dysfunction: a systematic review and meta-analysis.
        J Sex Med. 2014; 11: 1367-1375
        • Kostis J.B.
        • Dobrzynski J.M.
        The effect of statins on erectile dysfunction: a meta-analysis of randomized trials.
        J Sex Med. 2014; 11: 1626-1635
        • El-Sisi A.A.
        • Hegazy S.K.
        • Salem K.A.
        • AbdElkawy K.S.
        Atorvastatin improves erectile dysfunction in patients initially irresponsive to Sildenafil by the activation of endothelial nitric oxide synthase.
        Int J Impot Res. 2013; 25: 143-148
        • Trivedi D.
        • Wellsted D.M.
        • Collard J.B.
        • Kirby M.
        Simvastatin improves the sexual health-related quality of life in men aged 40 years and over with erectile dysfunction: additional data from the erectile dysfunction and statin trial.
        BMC Urol. 2014; 14: 24
        • Wise S.J.
        • Nathoo N.A.
        • Etminan M.
        • Mikelberg F.S.
        • Mancini G.B.
        Statin use and risk for cataract: a nested case-control study of 2 populations in Canada and the United States.
        Can J Cardiol. 2014; 30: 1613-1619
        • Chung S.D.
        • Tsai M.C.
        • Liu S.P.
        • Lin H.C.
        • Kang J.H.
        Herpes zoster is associated with prior statin use: a population-based case-control study.
        PLoS One. 2014; 9: e111268
        • Pietrzak A.
        • Mosiewicz J.
        • Chodorowska G.
        • et al.
        Eruption of palmoplantar pustular psoriasis in patient treated with anti-androgen therapy for prostate cancer and aggravation of lesions after statin treatment.
        Cent Eur J Med. 2014; 9: 657-662
        • Lo Schiavo A.
        • Puca R.V.
        • Romano F.
        • Cozzi R.
        Pemphigus erythematosus relapse associated with atorvastatin intake.
        Drug Des Devel Ther. 2014; 8: 1463-1465
        • Saad N.
        • Camus P.
        • Suissa S.
        • Ernst P.
        Statins and the risk of interstitial lung disease: a cohort study.
        Thorax. 2013; 68: 361-364
        • Vedel-Krogh S.
        • Nielsen S.F.
        • Nordestgaard B.G.
        Statin use is associated with reduced mortality in patients with interstitial lung disease.
        PLoS One. 2015; 10: e0140571