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Low-density lipoprotein reduction: Is the risk worth the benefit?

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Abstract

Outcomes from recent lipid-lowering trials have led to an update of the third Report of the National Cholesterol Education Program (NCEP) Adult Treatment Panel’s guidelines for treatment of hypercholesterolemia in adults. The updated NCEP guidelines now offer an optional goal of low-density lipoprotein (LDL) cholesterol of less than 70 mg/dL for high-risk individuals. Epidemiologic and clinical trial data suggest that for every 30-mg/dL change in LDL, the relative risk for coronary heart disease changes by about 30%. Statin therapy effectively lowers LDL and has an overall excellent safety profile in clinical trials. However, the use of high-dose statin therapy also entails greater risk of adverse events, such as myopathy and liver function test abnormalities, and this must be carefully weighed against the potential benefit for each patient. Alternative approaches targeting high-density lipoproteins and triglycerides may offer yet another option for coronary heart disease prevention in high-risk patients.

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References and Recommended Reading

  1. 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.

    Article  PubMed  Google Scholar 

  2. Waters DD, Guyton JR, Herrington DM, et al.: Treating to New Targets (TNT) Study: does lowering low-density lipoprotein cholesterol levels below currently recommended guidelines yield incremental clinical benefit? Am J Cardiol 2004, 93:154–158.

    Article  PubMed  Google Scholar 

  3. O’Keefe JH Jr, Cordain L, Harris WH, et al.: Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol 2004, 43:2142–2146.

    Article  PubMed  CAS  Google Scholar 

  4. Shepherd J, Blauw GJ, Murphy MB, et al.: Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002, 360:1623–1630.

    Article  PubMed  CAS  Google Scholar 

  5. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA 2002, 288:2998–3007.

  6. Pasternak RC: The ALLHAT lipid lowering trial—less is less. JAMA 2002, 288:3042–3044.

    Article  PubMed  Google Scholar 

  7. Sever PS, Dahlof B, Poulter NR, et al.: Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003, 361:1149–1158.

    Article  PubMed  CAS  Google Scholar 

  8. Colhoun HM, Betteridge DJ, Durrington PN, et al.: Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004, 364:685–696.

    Article  PubMed  CAS  Google Scholar 

  9. Wanner C, Krane V, Marz W, et al.: Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005, 353:238–248.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

  11. Nissen SE, Tuzcu EM, Schoenhagen P, et al.: Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 2004, 291:1071–1080.

    Article  PubMed  CAS  Google Scholar 

  12. Schwartz GG, Olsson AG, Ezekowitz MD, 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.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. de Lemos JA, Blazing MA, Wiviott SD, et al.: Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004, 292:1307–1316.

    Article  PubMed  Google Scholar 

  15. 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.

    Article  PubMed  Google Scholar 

  16. Thompson PD, Clarkson P, Karas RH: Statin-associated myopathy. JAMA 2003, 289:1681–1690.

    Article  PubMed  CAS  Google Scholar 

  17. Sacher J, Weigl L, Werner M, et al.: Delineation of myotoxicity induced by HMG-CoA-reductase-inhibitors in human skeletal muscle cells. J Pharmacol Exp Ther 2005, In press.

  18. Bellosta S, Paoletti R, Corsini A: Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation 2004, 109(23 Suppl 1):III50-III57.

    PubMed  Google Scholar 

  19. Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, et al.: Total cholesterol and risk of mortality in the oldest old. Lancet 1997, 350:1119–1123.

    Article  PubMed  CAS  Google Scholar 

  20. Fassbender K, Simons M, Bergmann C, et al.: Simvastatin strongly reduces levels of Alzheimer’s disease beta-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proc Natl Acad Sci U S A 2001, 98:5856–5861.

    Article  PubMed  CAS  Google Scholar 

  21. Dufouil C, Richard F, Fievet N, et al.: APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: the Three-City Study. Neurology 2005, 64:1531–1538.

    Article  PubMed  CAS  Google Scholar 

  22. Jick H, Zornberg GL, Jick SS, et al.: Statins and the risk of dementia. Lancet 2000, 356:1627–1631.

    Article  PubMed  CAS  Google Scholar 

  23. Rea TD, Breitner JC, Psaty BM, et al.: Statin use and the risk of incident dementia: the Cardiovascular Health Study. Arch Neurol 2005, 62:1047–1051.

    Article  PubMed  Google Scholar 

  24. Backes JM, Howard PA: Association of HMG-CoA reductase inhibitors with neuropathy. Ann Pharmacother 2003, 37:274–278.

    Article  PubMed  CAS  Google Scholar 

  25. Gaist D, Garcia Rodriguez LA, Huerta C, et al.: Are users of lipid-lowering drugs at increased risk of peripheral neuropathy? Eur J Clin Pharmacol 2001, 56:931–933.

    Article  PubMed  CAS  Google Scholar 

  26. Gaist D, Jeppesen U, Andersen M, et al.: Statins and risk of polyneuropathy: a case-control study. Neurology 2002, 58:1333–1337.

    PubMed  CAS  Google Scholar 

  27. Rubins HB, Robins SJ, Collins D, et al.: Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999, 341:410–418.

    Article  PubMed  CAS  Google Scholar 

  28. Robins SJ, Collins D, Wittes JT, et al.: Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA 2001, 285:1585–1591.

    Article  PubMed  CAS  Google Scholar 

  29. LaRosa JC, Gotto AM Jr: Past, present, and future standards for management of dyslipidemia. Am J Med 2004, 116(Suppl 6A):3S-8S.

    Article  PubMed  Google Scholar 

  30. Brown BG, Zhao XQ, Chait A, et al.: Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001, 345:1583–1592.

    Article  PubMed  CAS  Google Scholar 

  31. Brousseau ME, Schaefer EJ, Wolfe MI, et al.: Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med 2004, 350:1505–1515.

    Article  PubMed  CAS  Google Scholar 

  32. Ong HT: The statin studies: from targeting hypercholesterolaemia to targeting the high-risk patient. Quart J Med 2005, 98:599–614.

    CAS  Google Scholar 

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Correspondence to Jeffrey B. Boord MD.

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Sabharwal, A.K., Boord, J.B. Low-density lipoprotein reduction: Is the risk worth the benefit?. Curr Atheroscler Rep 8, 19–25 (2006). https://doi.org/10.1007/s11883-006-0060-6

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  • DOI: https://doi.org/10.1007/s11883-006-0060-6

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