Abstract
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are among the most commonly prescribed and studied drugs in modern medicine. Their proven benefit in prevention of cardiovascular events is driven by their ability to markedly reduce low-density lipoprotein cholesterol (LDL-C). Recent analyses have provided insight into the relationship between statin-induced reductions in LDL-C and risk of rhabdomyolysis, liver toxicity, and cancer. Risk of statin-associated elevated liver enzymes and rhabdomyolysis is not related to the magnitude of LDL-C lowering. Instead, drug- and dose-specific effects of statins are more important determinants of liver and muscle toxicity than magnitude of LDL-C lowering. Furthermore, although there is an inverse association between LDL-C and cancer risk in both statin-treated and comparable control cohorts, statin therapy, despite significantly reducing LDL-C, is not associated with an increased risk of cancer.
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References and Recommended Reading
Grundy SM, Cleeman JI, Merz CN, et al.: Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004, 110:227–239.
Baigent C, Keech A, Kearney PM, 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.
Ridker PM, Cannon CP, Morrow D, et al.: C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005, 352: 20–28.
Ridker PM, Morrow DA, Rose LM, et al.: Relative efficacy of atorvastatin 80 mg and pravastatin 40 mg in achieving the dual goals of low-density lipoprotein cholesterol <70 mg/dl and C-reactive protein <2 mg/l: an analysis of the PROVE-IT TIMI-22 trial. J Am Coll Cardiol 2005, 45: 1644–1648.
Corti R, Fuster V, Fayad ZA, et al.: Effects of aggressive versus conventional lipid-lowering therapy by simvastatin on human atherosclerotic lesions: a prospective, randomized, double-blind trial with high-resolution magnetic resonance imaging. J Am Coll Cardiol 2005, 46: 106–112.
Robinson JG, Smith B, Maheshwari N, Schrott H: Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis. J Am Coll Cardiol 2005, 46:1855–1862.
Staffa JA, Chang J, Green L: Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med 2002, 346:539–540.
Alsheikh-Ali AA, Ambrose MS, Kuvin JT, Karas RH: The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis. Circulation 2005, 111:3051–3057.
Jacobs D, Blackburn H, Higgins M, et al.: Report of the Conference on Low Blood Cholesterol: mortality associations. Circulation 1992, 86: 1046–1060.
Alsheikh-Ali AA, Maddukuri PV, Han H, Karas RH: Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: insights from large randomized statin trials. J Am Coll Cardiol 2007, 50:409–418.
Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al.: ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. Circulation 2002, 106: 1024–1028.
Thompson PD, Clarkson P, Karas RH: Statin-associated myopathy. JAMA 2003, 289:1681–1690.
The SEARCH Collaborative Group: SLCO1B1 variants and statin-induced myopathy—a genomewide study. N Engl J Med 2008, 359:789–799.
Newman TB, Hulley SB: Carcinogenicity of lipid-lowering drugs. JAMA 1996, 275:55–60.
Bjerre LM, LeLorier J: Do statins cause cancer? A metaanalysis of large randomized clinical trials. Am J Med 2001, 110:716–723.
Dale KM, Coleman CI, Henyan NN, et al.: Statins and cancer risk: a meta-analysis. JAMA 2006, 295: 74–80.
Alsheikh-Ali AA, Trikalinos TA, Kent DM, Karas RH: Statins, low-density lipoprotein cholesterol, and risk of cancer. J Am Coll Cardiol 2008, 52:1141–1147.
Trikalinos TA, Ioannidis JP: Predictive modeling and heterogeneity of baseline risk in meta-analysis of individual patient data. J Clin Epidemiol 2001, 54:245–252.
Mudd JO, Borlaug BA, Johnston PV, et al.: Beyond low-density lipoprotein cholesterol: defining the role of low-density lipoprotein heterogeneity in coronary artery disease. J Am Coll Cardiol 2007, 50: 1735–1741.
Demierre MF, Higgins PD, Gruber SB, et al.: Statins and cancer prevention. Nat Rev 2005, 5: 930–942.
Rossebo AB, Pedersen TR, Boman K, et al.: Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008, 359:1343–1356.
Peto R, Emberson J, Landray M, et al.: Analyses of cancer data from three ezetimibe trials. N Engl J Med 2008, 359: 1357–1366.
Cannon CP, Braunwald E, McCabe CH, et al.: Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004, 350:1495–1504.
Feinleib M: Summary of a workshop on cholesterol and noncardiovascular disease mortality. Prevent Med 1982, 11:360–367.
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Alsheikh-Ali, A.A., Karas, R.H. The relationship of statins to rhabdomyolysis, malignancy, and hepatic toxicity: Evidence from clinical trials. Curr Atheroscler Rep 11, 100–104 (2009). https://doi.org/10.1007/s11883-009-0016-8
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DOI: https://doi.org/10.1007/s11883-009-0016-8