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Statin-associated adverse effects beyond muscle and liver toxicity

      Abstract

      Randomized controlled trials with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have consistently demonstrated significant reductions in cardiovascular morbidity and mortality. Statins are currently the most widely used drugs in many countries. The most important adverse effects are associated with muscle and liver toxicity. However, with increased use and dose of statins and their over-the-counter availability in some countries more cases of other rare side effects may be seen in clinical practice. In the present article we review the literature concerning the statin-related adverse effects other than muscle and liver injury and we provide insight into their clinical revelance and possible underlying mechanisms.

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      References

        • Sacks F.M.
        • Pfeffer M.A.
        • Moye L.A.
        • et al.
        The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators.
        N Engl J Med. 1996; 335: 1001-1009
      1. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).
        Lancet. 1994; 344: 1383-1389
        • Athyros V.G.
        • Papageorgiou A.A.
        • Mercouris B.R.
        • et al.
        Treatment with atorvastatin to the National Cholesterol Educational Program goal versus ‘usual’ care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study.
        Curr Med Res Opin. 2002; 18: 220-228
        • Schwartz G.G.
        • Olsson A.G.
        • Ezekowitz M.D.
        • et al.
        Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.
        JAMA. 2001; 285: 1711-1718
        • Newman C.B.
        • Palmer G.
        • Silbershatz H.
        • Szarek M.
        Safety of atorvastatin derived from analysis of 44 completed trials in 9416 patients.
        Am J Cardiol. 2003; 92: 670-676
        • Pasternak R.C.
        • Smith S.C.
        • Bairey-Merz C.N.
        • et al.
        ACC/AHA/NHLBI clinical advisory on the use and safety of statins.
        Stroke. 2002; 33: 2337-2341
        • Jones P.
        • Kafonek S.
        • Laurora I.
        • Hunninghake D.
        Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study).
        Am J Cardiol. 1998; 81: 582-587
        • Ballantyne C.M.
        • Blazing M.A.
        • Hunninghake D.B.
        • et al.
        Effect on high-density lipoprotein cholesterol of maximum dose simvastatin and atorvastatin in patients with hypercholesterolemia: results of the Comparative HDL Efficacy and Safety Study (CHESS).
        Am Heart J. 2003; 146: 862-869
        • El-Hajj I.I.
        • Mourad F.H.
        • Shabb N.S.
        • Barada K.A.
        Atorvastatin-induced severe gastric ulceration: a case report.
        World J Gastroenterol. 2005; 11: 3159-3160
        • Batey R.G.
        • Harvey M.
        Cholestasis associated with the use of pravastatin sodium.
        Med J Aust. 2002; 176: 561
        • Yoshida E.M.
        • Levin A.
        Lovastatin and cholestasis.
        CMAJ. 1993; 148: 374
        • Rea W.E.
        • Durrant D.C.
        • Boldy D.A.
        Ulcerative colitis after statin treatment.
        Postgrad Med J. 2002; 78: 286-287
        • Miltiadous G.
        • Anthopoulou A.
        • Elisaf M.
        Acute pancreatitis possibly associated with combined salicylate and atorvastatin therapy.
        JOP. 2003; 4: 20-21
        • Tysk C.
        • Al-Eryani A.Y.
        • Shawabkeh A.A.
        Acute pancreatitis induced by fluvastatin therapy.
        J Clin Gastroenterol. 2002; 35: 406-408
        • Pezzilli R.
        • Ceciliato R.
        • Corinaldesi R.
        • Barakat B.
        Acute pancreatitis due to simvastatin therapy: increased severity after rechallenge.
        Dig Liver Dis. 2004; 36: 639-640
        • Johnson J.L.
        • Loomis I.B.
        A case of simvastatin-associated pancreatitis and review of statin-associated pancreatitis.
        Pharmacotherapy. 2006; 26: 414-422
        • Singh S.
        • Nautiyal A.
        • Dolan J.G.
        Recurrent acute pancreatitis possibly induced by atorvastatin and rosuvastatin. Is statin induced pancreatitis a class effect?.
        JOP. 2004; 5: 502-504
        • Lons T.
        • Chousterman M.
        Simvastatin: a new drug responsible for acute pancreatitis?.
        Gastroenterol Clin Biol. 1991; 15 ([in French]): 93-94
        • Belaiche G.
        • Ley G.
        • Slama J.L.
        Acute pancreatitis associated with atorvastatin therapy.
        Gastroenterol Clin Biol. 2000; 24 ([in French]): 471-472
        • Singh S.
        Drug induced pancreatitis might be a class effect of statin drugs.
        JOP. 2005; 6: 380
        • Anagnostopoulos G.K.
        • Tsiakos S.
        • Margantinis G.
        • Kostopoulos P.
        • Arvanitidis D.
        Acute pancreatitis due to pravastatin therapy.
        JOP. 2003; 4: 129-132
        • Thisted H.
        • Jacobsen J.
        • Munk E.M.
        • et al.
        Statins and the risk of acute pancreatitis: a population-based case–control study.
        Aliment Pharmacol Ther. 2006; 23: 185-190
        • Segal A.S.
        Alopecia associated with atorvastatin.
        Am J Med. 2002; 113: 171
        • Krasovec M.
        • Elsner P.
        • Burg G.
        Generalized eczematous skin rash possibly due to HMG-CoA reductase inhibitors.
        Dermatology. 1993; 186: 248-252
        • Mehregan D.R.
        • Mehregan D.A.
        • Pakideh S.
        Cheilitis due to treatment with simvastatin.
        Cutis. 1998; 62: 197-198
        • Pua V.S.
        • Scolyer R.A.
        • Barnetson R.S.
        Pravastatin-induced lichenoid drug eruption.
        Australas J Dermatol. 2006; 47: 57-59
        • Adcock B.B.
        • Hornsby L.B.
        • Jenkins K.
        Dermographism: an adverse effect of atorvastatin.
        J Am Board Fam Pract. 2001; 14: 148-151
        • Anliker M.D.
        • Wuthrich B.
        Chronic urticaria to atorvastatin.
        Allergy. 2002; 57: 366
        • Pfeiffer C.M.
        • Kazenoff S.
        • Rothberg H.D.
        Toxic epidermal necrolysis from atorvastatin.
        JAMA. 1998; 279: 1613-1614
        • Gerson R.J.
        • MacDonald J.S.
        • Alberts A.W.
        • et al.
        On the etiology of subcapsular lenticular opacities produced in dogs receiving HMG-CoA reductase inhibitors.
        Exp Eye Res. 1990; 50: 65-78
        • Adamska-Dyniewska H.
        • Chojnowska-Jezierska J.
        • Cybulska B.
        • et al.
        Lovastatin in the treatment of hypercholesterolemia.
        Pol Arch Med Wewn. 1994; 92 ([in Polish]): 54-62
        • Bousquet E.
        • Amar J.
        • Salvador M.
        • Chamontin B.
        Cataract and simvastatin: case report.
        Therapie. 1998; 53 ([in French]): 505-507
        • Schlienger R.G.
        • Haefeli W.E.
        • Jick H.
        • Meier C.R.
        Risk of cataract in patients treated with statins.
        Arch Intern Med. 2001; 161: 2021-2026
        • Smeeth L.
        • Hubbard R.
        • Fletcher A.E.
        Cataract and the use of statins: a case–control study.
        QJM. 2003; 96: 337-343
        • Klein B.E.
        • Klein R.
        • Lee K.E.
        • Grady L.M.
        Statin use and incident nuclear cataract.
        JAMA. 2006; 295: 2752-2758
        • Fraunfelder F.W.
        Ocular hemorrhage possibly the result of HMG-CoA reductase inhibitors.
        J Ocul Pharmacol Ther. 2004; 20: 179-182
        • Bucca C.
        • Marsico A.
        • Panaro E.
        • Bigo P.
        • Brussino L.
        Statins and nasal polyps.
        Ann Intern Med. 2005; 142: 310-311
        • Muldoon M.F.
        • Manuck S.B.
        • Matthews K.A.
        Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials.
        BMJ. 1990; 301: 309-314
      2. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial.
        Lancet. 2002; 360: 7-22
        • Baigent C.
        • Keech A.
        • Kearney P.M.
        • et al.
        Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.
        Lancet. 2005; 366: 1267-1278
        • Muldoon M.F.
        • Manuck S.B.
        • Mendelsohn A.B.
        • Kaplan J.R.
        • Belle S.H.
        Cholesterol reduction and non-illness mortality: meta-analysis of randomised clinical trials.
        BMJ. 2001; 322: 11-15
        • Keller S.
        • Frishman W.H.
        Neuropsychiatric effects of cardiovascular drug therapy.
        Cardiol Rev. 2003; 11: 73-93
        • Stewart R.A.
        • Sharples K.J.
        • North F.M.
        • et al.
        Long-term assessment of psychological well-being in a randomized placebo-controlled trial of cholesterol reduction with pravastatin. The LIPID Study Investigators.
        Arch Intern Med. 2000; 160: 3144-3152
        • Boumendil E.
        • Tubert-Bitter P.
        Depression-induced absenteeism in relation to antihyperlipidemic treatment: a study using GAZEL cohort data.
        Epidemiology. 1995; 6: 322-325
        • Duits N.
        • Bos F.M.
        Depressive symptoms and cholesterol-lowering drugs.
        Lancet. 1993; 341: 114
        • Rosenson R.S.
        • Goranson N.L.
        Lovastatin-associated sleep and mood disturbances.
        Am J Med. 1993; 95: 548-549
        • Ehrenberg B.L.
        • Lamon-Fava S.
        • Corbett K.E.
        • et al.
        Comparison of the effects of pravastatin and lovastatin on sleep disturbance in hypercholesterolemic subjects.
        Sleep. 1999; 22: 117-121
        • Gregoor P.J.
        Atorvastatin may cause nightmares.
        BMJ. 2006; 332: 950
        • Boriani G.
        • Biffi M.
        • Strocchi E.
        • Branzi A.
        Nightmares and sleep disturbances with simvastatin and metoprolol.
        Ann Pharmacother. 2001; 35: 1292
        • Vgontzas A.N.
        • Kales A.
        • Bixler E.O.
        • Manfredi R.L.
        • Tyson K.L.
        Effects of lovastatin and pravastatin on sleep efficiency and sleep stages.
        Clin Pharmacol Ther. 1991; 50: 730-737
        • Roth T.
        • Richardson G.R.
        • Sullivan J.P.
        • et al.
        Comparative effects of pravastatin and lovastatin on nighttime sleep and daytime performance.
        Clin Cardiol. 1992; 15: 426-432
        • Orsi A.
        • Sherman O.
        • Woldeselassie Z.
        Simvastatin-associated memory loss.
        Pharmacotherapy. 2001; 21: 767-769
        • King D.S.
        • Wilburn A.J.
        • Wofford M.R.
        • et al.
        Cognitive impairment associated with atorvastatin and simvastatin.
        Pharmacotherapy. 2003; 23: 1663-1667
        • Bollen E.L.
        • Gaw A.
        • Buckley B.M.
        Statin therapy and the prevention of dementia.
        Arch Neurol. 2001; 58: 1023-1024
        • Etminan M.
        • Gill S.
        • Samii A.
        The role of lipid-lowering drugs in cognitive function: a meta-analysis of observational studies.
        Pharmacotherapy. 2003; 23: 726-730
        • Gurm H.S.
        • Hoogwerf B.
        The Heart Protection Study: high-risk patients benefit from statins, regardless of LDL-C level.
        Cleve Clin J Med. 2003; 70: 991-997
        • Liberopoulos E.N.
        • Mikhailidis D.P.
        Could statins be useful in the treatment of patients with migraine?.
        Headache. 2006; 46: 672-675
        • Ramsey C.S.
        • Snyder Q.C.
        Altitude-induced migraine headache secondary to pravastatin: case report.
        Aviat Space Environ Med. 1998; 69: 603-606
        • Vollmer T.
        • Key L.
        • Durkalski V.
        • et al.
        Oral simvastatin treatment in relapsing-remitting multiple sclerosis.
        Lancet. 2004; 363: 1607-1608
        • Golomb B.A.
        • Criqui M.H.
        • White H.L.
        • Dimsdale J.E.
        The UCSD Statin Study: a randomized controlled trial assessing the impact of statins on selected noncardiac outcomes.
        Contr Clin Trials. 2004; 25: 178-202
        • Ahmad S.
        Lovastatin and peripheral neuropathy.
        Am Heart J. 1995; 130: 1321
        • Chong P.H.
        • Boskovich A.
        • Stevkovic N.
        • Bartt R.E.
        Statin-associated peripheral neuropathy: review of the literature.
        Pharmacotherapy. 2004; 24: 1194-1203
        • Jeppesen U.
        • Gaist D.
        • Smith T.
        • Sindrup S.H.
        Statins and peripheral neuropathy.
        Eur J Clin Pharmacol. 1999; 54: 835-838
        • Rajabally Y.A.
        • Varakantam V.
        • Abbott R.J.
        Disorder resembling Guillain–Barre syndrome on initiation of statin therapy.
        Muscle Nerve. 2004; 30: 663-666
        • Gaist D.
        • Garcia Rodriguez L.A.
        • Huerta C.
        • Hallas J.
        • Sindrup S.H.
        Are users of lipid-lowering drugs at increased risk of peripheral neuropathy?.
        Eur J Clin Pharmacol. 2001; 56: 931-933
        • Gaist D.
        • Jeppesen U.
        • Andersen M.
        • et al.
        Statins and risk of polyneuropathy: a case–control study.
        Neurology. 2002; 58: 1333-1337
        • Corrao G.
        • Zambon A.
        • Bertu L.
        • et al.
        Lipid lowering drugs prescription and the risk of peripheral neuropathy: an exploratory case–control study using automated databases.
        J Epidemiol Commun Health. 2004; 58: 1047-1051
        • Anderson J.L.
        • Muhlestein J.B.
        • Bair T.L.
        • et al.
        Do statins increase the risk of idiopathic polyneuropathy?.
        Am J Cardiol. 2005; 95: 1097-1099
        • Phan T.
        • McLeod J.G.
        • Pollard J.D.
        • et al.
        Peripheral neuropathy associated with simvastatin.
        J Neurol Neurosurg Psychiatry. 1995; 58: 625-628
        • Rosch P.J.
        Peripheral neuropathy.
        Lancet. 2004; 364: 1663-1664
        • Jackson G.
        Erectile dysfunction and cardiovascular disease.
        Int J Clin Pract. 1999; 53: 363-368
        • Rizvi K.
        • Hampson J.P.
        • Harvey J.N.
        Do lipid-lowering drugs cause erectile dysfunction? A systematic review.
        Fam Pract. 2002; 19: 95-98
        • Bruckert E.
        • Giral P.
        • Heshmati H.M.
        • Turpin G.
        Men treated with hypolipidaemic drugs complain more frequently of erectile dysfunction.
        J Clin Pharm Ther. 1996; 21: 89-94
        • Halkin A.
        • Lossos I.S.
        • Mevorach D.
        HMG-CoA reductase inhibitor-induced impotence.
        Ann Pharmacother. 1996; 30: 192
        • de Graaf L.
        • Brouwers A.H.
        • Diemont W.L.
        Is decreased libido associated with the use of HMG-CoA-reductase inhibitors?.
        Br J Clin Pharmacol. 2004; 58: 326-328
        • Jay R.H.
        • Sturley R.H.
        • Stirling C.
        • et al.
        Effects of pravastatin and cholestyramine on gonadal and adrenal steroid production in familial hypercholesterolaemia.
        Br J Clin Pharmacol. 1991; 32: 417-422
        • Aerts J.
        • Karmochkine M.
        • Raguin G.
        Gynecomastia due to pravastatin.
        Presse Med. 1999; 28 ([in French]): 787
        • Undas A.
        • Brummel K.E.
        • Musial J.
        • Mann K.G.
        • Szczeklik A.
        Simvastatin depresses blood clotting by inhibiting activation of prothrombin, factor V, and factor XIII and by enhancing factor Va inactivation.
        Circulation. 2001; 103: 2248-2253
        • Szczeklik A.
        • Undas A.
        • Musial J.
        • et al.
        Antithrombotic actions of statins.
        Med Sci Monit. 2001; 7: 1381-1385
        • Tsiara S.
        • Elisaf M.
        • Mikhailidis D.P.
        Early vascular benefits of statin therapy.
        Curr Med Res Opin. 2003; 19: 540-556
        • Liberopoulos E.N.
        • Daskalopoulou S.S.
        • Mikhailidis D.P.
        Early statin therapy in patients with acute coronary syndrome.
        Hellenic J Cardiol. 2005; 46: 5-8
        • Groneberg D.A.
        • Barkhuizen A.
        • Jeha T.
        Simvastatin-induced thrombocytopenia.
        Am J Hematol. 2001; 67: 277
        • McCarthy L.J.
        • Porcu P.
        • Fausel C.A.
        • Sweeney C.J.
        • Danielson C.F.
        Thrombotic thrombocytopenic purpura and simvastatin.
        Lancet. 1998; 352: 1284-1285
        • Koduri P.R.
        Simvastatin and thrombotic thrombocytopenic purpura.
        Lancet. 1998; 352: 2020
        • Sundram F.
        • Roberts P.
        • Kennedy B.
        • Pavord S.
        Thrombotic thrombocytopenic purpura associated with statin treatment.
        Postgrad Med J. 2004; 80: 551-552
        • Nikolsky E.
        • Sadeghi H.M.
        • Effron M.B.
        • et al.
        Impact of in-hospital acquired thrombocytopenia in patients undergoing primary angioplasty for acute myocardial infarction.
        Am J Cardiol. 2005; 96: 474-481
        • Antons K.A.
        • Williams C.D.
        • Baker S.K.
        • Phillips P.S.
        Clinical perspectives of statin-induced rhabdomyolysis.
        Am J Med. 2006; 119: 400-409
        • Agarwal R.
        Effects of statins on renal function.
        Am J Cardiol. 2006; 97: 748-755
        • Vidt D.G.
        • Cressman M.D.
        • Harris S.
        • Pears J.S.
        • Hutchinson H.G.
        Rosuvastatin-induced arrest in progression of renal disease.
        Cardiology. 2004; 102: 52-60
      3. Kostapanos M, Milionis H, Gazi I, et al. Rosuvastatin increases alpha-1 microglobulin urinary excretion in patients with primary dyslipidemia. J Clin Pharmacology; in press.

        • Weber M.H.
        • Verwiebe R.
        Alpha 1-microglobulin (protein HC): features of a promising indicator of proximal tubular dysfunction.
        Eur J Clin Chem Clin Biochem. 1992; 30: 683-691
        • Verhulst A.
        • D’Haese P.C.
        • De Broe M.E.
        Inhibitors of HMG-CoA reductase reduce receptor-mediated endocytosis in human kidney proximal tubular cells.
        J Am Soc Nephrol. 2004; 15: 2249-2257
        • Sidaway J.E.
        • Davidson R.G.
        • McTaggart F.
        • et al.
        Inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase reduce receptor-mediated endocytosis in opossum kidney cells.
        J Am Soc Nephrol. 2004; 15: 2258-2265
        • Agarwal R.
        • Curley T.M.
        The role of statins in chronic kidney disease.
        Am J Med Sci. 2005; 330: 69-81
        • Tiwari A.
        An overview of statin-associated proteinuria.
        Drug Discov Today. 2006; 11: 458-464
        • van Zyl-Smit R.
        • Firth J.C.
        • Duffield M.
        • Marais A.D.
        Renal tubular toxicity of HMG-CoA reductase inhibitors.
        Nephrol Dial Transplant. 2004; 19: 3176-3179
        • Tonolo G.
        • Ciccarese M.
        • Brizzi P.
        • et al.
        Reduction of albumin excretion rate in normotensive microalbuminuric type 2 diabetic patients during long-term simvastatin treatment.
        Diabetes Care. 1997; 20: 1891-1895
        • Tonolo G.
        • Melis M.G.
        • Formato M.
        • et al.
        Additive effects of simvastatin beyond its effects on LDL cholesterol in hypertensive type 2 diabetic patients.
        Eur J Clin Invest. 2000; 30: 980-987
        • Athyros V.G.
        • Mikhailidis D.P.
        • Papageorgiou A.A.
        • et al.
        The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study.
        J Clin Pathol. 2004; 57: 728-734
        • Liberopoulos E.N.
        • Mikhailidis D.P.
        • Athyros V.G.
        • Elisaf M.S.
        The effect of cholesterol-lowering treatment on renal function.
        Am J Kidney Dis. 2006; 47: 561
        • Kakafika A.
        • Liamis G.
        • Elisaf M.
        • Mikhailidis D.
        Effect of atorvastatin on serum creatinine levels.
        Curr Med Res Opin. 2001; 17: 230-231
        • Elisaf M.
        • Mikhailidis D.P.
        Statins and renal function.
        Angiology. 2002; 53: 493-502
        • Collins R.
        • Armitage J.
        • Parish S.
        • Sleigh P.
        • Peto R.
        MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial.
        Lancet. 2003; 361: 2005-2016
        • Tsouli S.G.
        • Liberopoulos E.N.
        • Athyros V.G.
        • Mikhailidis D.P.
        • Elisaf M.S.
        Elevated serum uric acid levels in metabolic syndrome: an active component or an innocent bystander?.
        Metabolism. 2006; 55: 1293-1301
        • Athyros V.G.
        • Elisaf M.
        • Papageorgiou A.A.
        • et al.
        Effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary heart disease: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study.
        Am J Kidney Dis. 2004; 43: 589-599
        • Kakafika A.
        • Tsimihodimos V.
        • Elisaf M.
        Effect of atorvastatin on serum uric acid levels.
        Atherosclerosis. 2001; 158: 255
        • Milionis H.J.
        • Kakafika A.I.
        • Tsouli S.G.
        • et al.
        Effects of statin treatment on uric acid homeostasis in patients with primary hyperlipidemia.
        Am Heart J. 2004; 148: 635-640
        • Milionis H.J.
        • Liberopoulos E.N.
        • Achimastos A.
        • Elisaf M.S.
        • Mikhailidis D.P.
        Statins: another class of antihypertensive agents?.
        J Hum Hypertens. 2006; 20: 320-335
        • Hanson J.
        • Bossingham D.
        Lupus-like syndrome associated with simvastatin.
        Lancet. 1998; 352: 1070
        • Noel B.
        • Panizzon R.G.
        Lupus-like syndrome associated with statin therapy.
        Dermatology. 2004; 208: 276-277
        • Quiceno G.A.
        • Cush J.J.
        Iatrogenic rheumatic syndromes in the elderly.
        Clin Geriatr Med. 2005; 21 (vii): 577-588
        • Vasconcelos O.M.
        • Campbell W.W.
        Dermatomyositis-like syndrome and HMG-CoA reductase inhibitor (statin) intake.
        Muscle Nerve. 2004; 30: 803-807
        • Giordano N.
        • Senesi M.
        • Mattii G.
        • et al.
        Polymyositis associated with simvastatin.
        Lancet. 1997; 349: 1600-1601
        • Pelli N.
        • Setti M.
        Atorvastatin as a trigger of autoimmune hepatitis.
        J Hepatol. 2004; 40: 716
        • Wolters L.M.
        • Van Buuren H.R.
        Rosuvastatin-associated hepatitis with autoimmune features.
        Eur J Gastroenterol Hepatol. 2005; 17: 589-590
        • Liebhaber M.I.
        • Wright R.S.
        • Gelberg H.J.
        • Dyer Z.
        • Kupperman J.L.
        Polymyalgia, hypersensitivity pneumonitis and other reactions in patients receiving HMG-CoA reductase inhibitors: a report of ten cases.
        Chest. 1999; 115: 886-889
        • Lantuejoul S.
        • Brambilla E.
        • Brambilla C.
        • Devouassoux G.
        Statin-induced fibrotic nonspecific interstitial pneumonia.
        Eur Respir J. 2002; 19: 577-580
        • McCarey D.W.
        • McInnes I.B.
        • Madhok R.
        • et al.
        Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial.
        Lancet. 2004; 363: 2015-2021
        • Shepherd J.
        • Blauw G.J.
        • Murphy M.B.
        • et al.
        Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.
        Lancet. 2002; 360: 1623-1630
        • Bjerre L.M.
        • LeLorier J.
        Do statins cause cancer? A meta-analysis of large randomized clinical trials.
        Am J Med. 2001; 110: 716-723
        • Poynter J.N.
        • Gruber S.B.
        • Higgins P.D.
        • et al.
        Statins and the risk of colorectal cancer.
        N Engl J Med. 2005; 352: 2184-2192
        • Dale K.M.
        • Coleman C.I.
        • Henyan N.N.
        • Kluger J.
        • White C.M.
        Statins and cancer risk: a meta-analysis.
        JAMA. 2006; 295: 74-80