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An Assessment of Statin Safety by Muscle Experts

Published:February 09, 2006DOI:https://doi.org/10.1016/j.amjcard.2005.12.013
      The National Lipid Association’s (NLA) Muscle Safety Expert Panel was charged with the duty of examining the definitions, causative factors, and management of statin myopathy. The Panel was asked to use its evidence-based findings to form recommendations in response to a series of specific questions posed by the Task Force. The panel was composed of a clinical cardiologist, an exercise physiologist and skeletal muscle expert, and an expert in preventive cardiology who also examined skeletal muscle complications of statin use.
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      References

        • Thompson P.D.
        • Clarkson P.
        • Karas R.H.
        Statin-associated myopathy.
        JAMA. 2003; 289: 1681-1690
        • Pasternak R.C.
        • Smith S.C.
        • Bairey-Merz C.N.
        • Grundy S.M.
        • Cleeman J.I.
        • Lenfant C.
        ACC/AHA/NHLBI clinical advisory on the use and safety of statins.
        J Am Coll Cardiol. 2002; 40: 567-572
        • Pierce L.R.
        • Wysowski D.K.
        • Gross T.P.
        Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy.
        JAMA. 1990; 264: 71-75
        • Ballantyne C.M.
        • Corsini A.
        • Davidson M.H.
        • Holdaas H.
        • Jacobson T.A.
        • Leitersdorf E.
        • Marz W.
        • Reckless J.P.
        • Stein E.A.
        Risk for myopathy with statin therapy in high-risk patients.
        Arch Intern Med. 2003; 163: 553-564
        • de Lemos J.A.
        • Blazing M.A.
        • Wiviott S.D.
        • Lewis E.F.
        • Fox K.A.
        • White H.D.
        • Rouleau J.L.
        • Pedersen T.R.
        • Gardner L.H.
        • Mukherjee R.
        • et al.
        Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes.
        JAMA. 2004; 292: 1307-1316
        • Clarkson P.M.
        • Hubal M.J.
        Exercise-induced muscle damage in humans.
        Am J Phys Med Rehabil. 2002; 81: S52-S69
        • Sayers S.P.
        • Clarkson P.M.
        • Rouzier P.A.
        • Kamen G.
        Adverse events associated with eccentric exercise protocols.
        Med Sci Sports Exerc. 1999; 31: 1697-1702
      1. Clarkson PM, Kearns AK, Rouzier P, Rubin R, Thompson PD. Serum creatine kinase levels and renal function measures in exertional muscle damage. Med Sci Sports Exerc. In press.

        • Black H.R.
        • Quallich H.
        • Gareleck C.B.
        Racial differences in serum creatine kinase levels.
        Am J Med. 1986; 81: 479-487
        • Fuhrmans V.
        Bayer discloses higher death toll from Baycol.
        Wall Street Journal. 2002; 21 (January): A10
        • Gharavi A.G.
        • Diamond J.A.
        • Smith D.A.
        • Phillips R.A.
        Niacin-induced myopathy.
        Am J Cardiol. 1994; 74: 841-842
        • Langer T.
        • Levy R.
        Acute muscular syndrome associated with administration of clofibrate.
        N Engl J Med. 1968; 279: 856-858
        • Graham D.J.
        • Staffa J.A.
        • Shatin D.
        • Andrade S.E.
        • Schech S.D.
        • La Grenade L.
        • Gurwitz J.H.
        • Chan K.A.
        • Goodman M.J.
        • Platt R.
        Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs.
        JAMA. 2004; 292: 2585-2590
        • Gaist D.
        • Rodriguez L.A.
        • Huerta C.
        • Hallas J.
        • Sindrup S.H.
        Lipid-lowering drugs and risk of myopathy.
        Epidemiology. 2001; 12: 565-569
        • Fux R.
        • Morike K.
        • Gundel U.F.
        • Hartmann R.
        • Gleiter C.H.
        Ezetimibe and statin-associated myopathy.
        Ann Intern Med. 2004; 140: 671-672
        • East C.
        • Alivizatos P.A.
        • Grundy S.M.
        • Jones P.H.
        • Farmer J.A.
        Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation.
        N Engl J Med. 1988; 318: 47-48
        • Davidson M.H.
        • Stein E.A.
        • Dujovne C.A.
        • Hunninghake D.B.
        • Weiss S.R.
        • Knopp R.H.
        • Illingworth D.R.
        • Mitchel Y.B.
        • Melino M.R.
        • Zupkis R.V.
        • et al.
        The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day.
        Am J Cardiol. 1997; 79: 38-42
        • Rosenson R.S.
        • Bays H.E.
        Results of two clinical trials on the safety and efficacy of pravastatin 80 and 160 mg per day.
        Am J Cardiol. 2003; 91: 878-881
      2. The statin wars.
        Lancet. 2003; 362: 1341
        • Hsiang B.
        • Zhu Y.
        • Wang Z.
        • Wu Y.
        • Sasseville V.
        • Yang W.P.
        • Kirchgessner T.G.
        A novel human hepatic organic anion transporting polypeptide (OATP2).
        J Biol Chem. 1999; 274: 37161-37168
        • Thompson P.D.
        • Nugent A.M.
        • Herbert P.N.
        Increases in creatine kinase after exercise in patients treated with HMG Co-A reductase inhibitors [letter].
        JAMA. 1990; 264: 2992
        • Thompson P.D.
        • Gadaleta P.A.
        • Yurgalevitch S.
        • Cullinane E.
        • Herbert P.N.
        Effects of exercise and lovastatin on serum creatine kinase activity.
        Metabolism. 1991; 40: 1333-1336
        • Thompson P.D.
        • Zmuda J.M.
        • Domalik L.J.
        • Zimet R.J.
        • Staggers J.
        • Guyton J.R.
        Lovastatin increases exercise-induced skeletal muscle injury.
        Metabolism. 1997; 46: 1206-1210
        • Rosenberg A.D.
        • Neuwirth M.G.
        • Kagen L.J.
        • Singh K.
        • Fischer H.D.
        • Bernstein R.L.
        Intraoperative rhabdomyolysis in a patient receiving pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor.
        Anesth Analg. 1995; 81: 1089-1091
        • Phillips P.S.
        • Haas R.H.
        • Bannykh S.
        • Hathaway S.
        • Gray N.L.
        • Kimura B.J.
        • Vladutiu G.D.
        • England J.D.
        Statin-associated myopathy with normal creatine kinase levels.
        Ann Intern Med. 2002; 137: 581-585
        • Shek A.
        • Ferrill M.J.
        Statin-fibrate combination therapy.
        Ann Pharmacother. 2001; 35: 908-917
        • Prueksaritanont T.
        • Zhao J.J.
        • Ma B.
        • Roadcap B.A.
        • Tang C.
        • Qiu Y.
        • Liu L.
        • Lin J.H.
        • Pearson P.G.
        • Baillie T.A.
        Mechanistic studies on metabolic interactions between gemfibrozil and statins.
        J Pharmacol Exp Ther. 2002; 301: 1042-1051
        • Prueksaritanont T.
        • Tang C.
        • Qiu Y.
        • Mu L.
        • Subramanian R.
        • Lin J.H.
        Effects of fibrates on metabolism of statins in human hepatocytes.
        Drug Metab Dispos. 2002; 30: 1280-1287
        • Hill M.D.
        • Bilbao J.M.
        Case of the month.
        Brain Pathol. 1999; 9: 607-608
        • Reaven P.
        • Witztum J.L.
        Lovastatin, nicotinic acid, and rhabdomyolysis.
        Ann Intern Med. 1988; 109: 597-598
        • Smith C.C.
        • Bernstein L.I.
        • Davis R.B.
        • Rind D.M.
        • Shmerling R.H.
        Screening for statin-related toxicity.
        Arch Intern Med. 2003; 163: 688-692
        • Smith D.J.
        • Olive K.E.
        Chinese red rice-induced myopathy.
        South Med J. 2003; 96: 1265-1267
        • Dahan A.
        • Altman H.
        Food-drug interaction.
        Eur J Clin Nutr. 2004; 58: 1-9
        • Flint O.P.
        • Masters B.A.
        • Gregg R.E.
        • Durham S.K.
        Inhibition of cholesterol synthesis by squalene synthase inhibitors does not induce myotoxicity in vitro.
        Toxicol Appl Pharmacol. 1997; 145: 91-98
        • Ghirlanda G.
        • Oradei A.
        • Manto A.
        • Lippa S.
        • Uccioli L.
        • Caputo S.
        • Greco A.V.
        • Littarru G.P.
        Evidence of plasma CoQ10-lowering effect by HMG-CoA reductase inhibitors.
        J Clin Pharmacol. 1993; 33: 226-229
        • Laaksonen R.
        • Riihimaki A.
        • Laitila J.
        • Martensson K.
        • Tikkanen M.J.
        • Himberg J.J.
        Serum and muscle tissue ubiquinone levels in healthy subjects.
        J Lab Clin Med. 1995; 125: 517-521
        • Laaksonen R.
        • Jokelainen K.
        • Laakso J.
        • Sahi T.
        • Harkonen M.
        • Tikkanen M.J.
        • Himberg J.J.
        The effect of simvastatin treatment on natural antioxidants in low-density lipoproteins and high-energy phosphates and ubiquinone in skeletal muscle.
        Am J Cardiol. 1996; 77: 851-854
        • Laaksonen R.
        • Ojala J.P.
        • Tikkanen M.J.
        • Himberg J.J.
        Serum ubiquinone concentrations after short- and long-term treatment with HMG-CoA reductase inhibitors.
        Eur J Clin Pharmacol. 1994; 46: 313-317
        • Laaksonen R.
        • Jokelainen K.
        • Sahi T.
        • Tikkanen M.J.
        • Himberg J.J.
        Decreases in serum ubiquinone concentrations do not result in reduced levels in muscle tissue during short-term simvastatin treatment in humans.
        Clin Pharmacol Ther. 1995; 57: 62-66
        • Paiva H.
        • Thelen K.M.
        • Van Coster R.
        • Smet J.
        • De Paepe B.
        • Mattila K.M.
        • Laakso J.
        • Lehtimaki T.
        • von Bergmann K.
        • Lutjohann D.
        • Laaksonen R.
        High-dose statins and skeletal muscle metabolism in humans.
        Clin Pharmacol Ther. 2005; 78: 60-68
        • Schaefer W.H.
        • Lawrence J.W.
        • Loughlin A.F.
        • Stoffregen D.A.
        • Mixson L.A.
        • Dean D.C.
        • Raab C.E.
        • Yu N.X.
        • Lankas G.R.
        • Frederick C.B.
        Evaluation of ubiquinone concentration and mitochondrial function relative to cerivastatin-induced skeletal myopathy in rats.
        Toxicol Appl Pharmacol. 2004; 194: 10-23
        • Kelly P.
        • Vasu S.
        • Getato M.
        • McNurlan M.
        • Lawson W.E.
        Coenzyme Q10 improves myopathic pain in statin treated patients.
        J Am Coll Cardiol. 2005; 45 ([abstract]): 3A