Drugs & Aging

, Volume 27, Issue 12, pp 959–972

Lipid Lowering for Secondary Prevention of Cardiovascular Disease in Older Adults

  • Joseph E. Thomas
  • Andrew M. Tershakovec
  • Charlotte Jones-Burton
  • Reza A. Sayeed
  • JoAnne M. Foody
Review Article

Abstract

A perceived lack of evidence for benefit and safety concerns may lead to underprescription of HMG-CoA reductase inhibitors (statins) in older adults. This article reviews clinical data regarding the effect of lipid-lowering therapies on cardiovascular outcomes in older adults with a focus on secondary prevention and safety considerations in this population. A literature search of the PubMed database (January 1984 to April 2009) was performed using search terms that included: ‘aged’ (MeSH heading), ‘elderly’, ‘anticholesteremic agents’, ‘antilipemic agents’, ‘hydroxymethylglutaryl-CoA reductase inhibitors’, ‘cardiovascular diseases’, ‘randomized controlled trial’, ‘meta-analysis’ and ‘drug safety’. Results from large, randomized, controlled trials show that statin therapy lowers both all-cause and coronary heart disease mortality and reduces myocardial infarction, stroke and the need for revascularization in individuals aged ≥65 years who have a history of coronary heart disease. Given the high rate of recurrent cardiovascular events in older adults, there is substantial potential for statin treatment to provide benefits in this population. When older patients are prescribed statins, attention should be given to potential drug interactions, age-related changes in drug pharmacokinetics, adverse effects such as myopathy and risks arising from co-morbid conditions. Additional studies on the benefits and risks of lipid-lowering therapy in individuals aged ≥70 years who have no history of cardiovascular disease, and particularly in those aged ≥80 years, are needed. Other available lipid-modifying drugs — bile acid sequestrants (bile acid binding protein modulators), ezetimibe, niacin and fibrates (fibric acid derivatives) — may be required in patients who are statin-intolerant or have mixed dyslipidaemia, or in whom standard doses of statins may not be sufficient to achieve low-density lipoprotein cholesterol goals.

References

  1. 1.
    World Health Organization. Fact sheet no. 317. Cardiovascular diseases [online]. Available from URL: http://www.who.int/mediacentre/factsheets/fs317/en/index.html [Accessed 2010 Mar 19]
  2. 2.
    Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics — 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009; 119: e21–181PubMedCrossRefGoogle Scholar
  3. 3.
    Ford ES, Giles WH, Mokdad AH. The distribution of 10-year risk for coronary heart disease among US adults: findings from the National Health and Nutrition Examination Survey III. J Am Coll Cardiol 2004 May; 43(10): 1791–6PubMedCrossRefGoogle Scholar
  4. 4.
    Manolio TA, Pearson TA, Wenger NK, et al. Cholesterol and heart disease in older persons and women: review of an NHLBI workshop. Ann Epidemiol 1992 Jan-Mar; 2(1–2): 161–76PubMedCrossRefGoogle Scholar
  5. 5.
    Kronmal RA, Cain KC, Ye Z, et al. Total serum cholesterol levels and mortality risk as a function of age: a report based on the Framingham data. Arch Intern Med 1993 May; 153(9): 1065–73PubMedCrossRefGoogle Scholar
  6. 6.
    Strandberg TE, Strandberg A, Rantanen K, et al. Low cholesterol, mortality, and quality of life in old age during a 39-year follow-up. J Am Coll Cardiol 2004; 44(5): 1002–8PubMedCrossRefGoogle Scholar
  7. 7.
    Wenger NK. Dyslipidemia as a risk factor at elderly age. Am J Geriatr Cardiol 2004 May–Jun; 13 (3 Suppl. 1): 4–9PubMedGoogle Scholar
  8. 8.
    Rubin SM, Sidney S, Black DM, et al. High blood cholesterol in elderly men and the excess risk for coronary heart disease. Ann Intern Med 1990 Dec; 113(12): 916–20PubMedGoogle Scholar
  9. 9.
    Benfante R, Reed D, Frank J. Do coronary heart disease risk factors measured in the elderly have the same predictive roles as in the middle aged: comparisons of relative and attributable risks. Ann Epidemiol 1992 May; 2(3): 273–82PubMedCrossRefGoogle Scholar
  10. 10.
    Amarenco P, Steg PG. The paradox of cholesterol and stroke. Lancet 2007 Dec; 370(9602): 1803–4PubMedCrossRefGoogle Scholar
  11. 11.
    Prospective Studies Collaboration. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths. Lancet 2007 Dec; 370(9602): 1829–39CrossRefGoogle Scholar
  12. 12.
    Curb JD, Abbott RD, Rodriguez BL, et al. High density lipoprotein cholesterol and the risk of stroke in elderly men: the Honolulu Heart Program. Am J Epidemiol 2004 Jul; 160(2): 150–7PubMedCrossRefGoogle Scholar
  13. 13.
    National Cholesterol Education Program. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002 Dec; 106(25): 3143–421Google Scholar
  14. 14.
    Ko DT, Mamdani M, Alter DA. Lipid-lowering therapy with statins in high-risk elderly patients: the treatment-risk paradox. JAMA 2004 Apr; 291(15): 1864–70PubMedCrossRefGoogle Scholar
  15. 15.
    Cournot M, Cambou JP, Quentzel S, et al. Key factors associated with the under-prescription of statins in elderly coronary heart disease patients: results from the ELIAGE and ELICOEUR surveys. Int J Cardiol 2006; 111: 12–8PubMedCrossRefGoogle Scholar
  16. 16.
    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 Oct; 366(9493): 1267–78PubMedCrossRefGoogle Scholar
  17. 17.
    Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18 686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008 Jan; 371(9607): 117–25PubMedCrossRefGoogle Scholar
  18. 18.
    Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002 Nov; 360(9346): 1623–30PubMedCrossRefGoogle Scholar
  19. 19.
    Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008 Nov; 359(21): 2195–207PubMedCrossRefGoogle Scholar
  20. 20.
    Poulter NR, Dahlof B, Sever PS, et al. Impact of atorvastatin on cardiovascular events in 2440 men and women aged 65 years and above: evidence from the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA) [abstract]. Stroke 2006; 37: 695Google Scholar
  21. 21.
    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 Apr; 361(9364): 1149–58PubMedCrossRefGoogle Scholar
  22. 22.
    Neil HA, DeMicco DA, Luo D, et al. Analysis of efficacy and safety in patients aged 65–75 years at randomization: Collaborative Atorvastatin Diabetes Study (CARDS). Diabetes Care 2006 Nov; 29(11): 2378–84PubMedCrossRefGoogle Scholar
  23. 23.
    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 Aug; 364(9435): 685–96PubMedCrossRefGoogle Scholar
  24. 24.
    Amarenco P, Bogousslavsky J, Callahan 3rd A, et al. Highdose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006 Aug; 355(6): 549–59PubMedCrossRefGoogle Scholar
  25. 25.
    Chaturvedi S, Zivin J, Breazna A, et al. Effect of atorvastatin in elderly patients with a recent stroke or transient ischemic attack. Neurology 2009 Feb; 72(8): 688–94PubMedCrossRefGoogle Scholar
  26. 26.
    Ali R, Alexander KP. Statins for the primary prevention of cardiovascular events in older adults: a review of the evidence. Am J Geriatr Pharmacother 2007 Mar; 5(1): 52–63PubMedCrossRefGoogle Scholar
  27. 27.
    Robinson JG, Bakris G, Torner J. Is it time for a cardiovascular primary prevention trial in the elderly? Stroke 2007 Feb; 38(2): 441–50PubMedCrossRefGoogle Scholar
  28. 28.
    Robinson JG. Lipid-lowering therapy for the primary prevention of cardiovascular disease in the elderly: opportunities and challenges. Drugs Aging 2009 Nov; 26(11): 917–31PubMedCrossRefGoogle Scholar
  29. 29.
    Goldstein LB, Amarenco P, Szarek M, et al. Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study. Neurology 2008 Jun; 70 (24 Pt 2): 2364–70PubMedCrossRefGoogle Scholar
  30. 30.
    Afilalo J, Duque G, Steele R, et al. Statins for secondary prevention in elderly patients: a hierarchical Bayesian metaanalysis. J Am Coll Cardiol 2008 Jan; 51(1): 37–45PubMedCrossRefGoogle Scholar
  31. 31.
    Welch HG, Albertsen PC, Nease RF, et al. Estimating treatment benefits for the elderly: the effect of competing risks. Ann Intern Med 1996 Mar; 124(6): 577–84PubMedGoogle Scholar
  32. 32.
    Tinetti ME, McAvay GJ, Fried TR, et al. Health outcome priorities among competing cardiovascular, fall injury, and medication-related symptom outcomes. J Am Geriatr Soc 2008 Aug; 56(8): 1409–16PubMedCrossRefGoogle Scholar
  33. 33.
    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 Jul; 110(2): 227–39PubMedCrossRefGoogle Scholar
  34. 34.
    Hunt D, Young P, Simes J, et al. Benefits of pravastatin on cardiovascular events and mortality in older patients with coronary heart disease are equal to or exceed those seen in younger patients: results from the LIPID trial. Ann Intern Med 2001 May; 134(10): 931–40PubMedGoogle Scholar
  35. 35.
    Miettinen TA, Pyorala K, Olsson AG, et al. Cholesterol-lowering therapy in women and elderly patients with myocardial infarction or angina pectoris: findings from the Scandinavian Simvastatin Survival Study (4S). Circulation 1997 Dec; 96(12): 4211–8PubMedCrossRefGoogle Scholar
  36. 36.
    Mevacor® (lovastatin) tablets: US prescribing information. Whitehouse Station (NJ): Merck, 2008 [online]. Available from URL: http://www.merck.com/product/usa/pi_circulars/m/mevacor/mevacor_pi.pdf [Accessed 2010 Mar 19]
  37. 37.
    Zocor® (simvastatin) tablets: US prescribing information. Whitehouse Station (NJ): Merck, 2008 [online]. Available from URL: http://www.merck.com/product/usa/pi_circulars/z/zocor/zocor_pi.pdf [Accessed 2010 Mar 19]
  38. 38.
    Lipitor® (atorvastatin calcium) tablets: US prescribing information. Dublin: Pfizer, 2009 [online]. Available from URL:http://www.pfizer.com/files/products/uspi_lipitor.pdf[Accessed 2010 Mar 19]
  39. 39.
    Crestor® (rosuvastatin calcium): US prescribing information. Wilmington (DE): AstraZeneca, 2009 [online]. Available from URL: http://www1.astrazeneca-us.com/pi/crestor.pdf [Accessed 2010 Mar 19]
  40. 40.
    Lescol® (fluvastatin sodium) capsules and Lescol® XL (fluvastatin sodium) extended-release tablets: US prescribing information. East Hanover (NJ): Novartis, 2006 [online]. Available from URL: http://www.pharma.us.novartis.com/product/pi/pdf/Lescol.pdf [Accessed 2010 Mar 19]
  41. 41.
    Pravachol® (pravastatin sodium) tablets: US prescribing information. Princeton (NJ): Bristol-Myers Squibb, 2007 [online]. Available from URL: http://packageinserts.bms.com/pi/pi_pravachol.pdf [Accessed 2010 Mar 19]
  42. 42.
    Pasternak RC, Smith Jr SC, Bairey-Merz CN, et al. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. Circulation 2002 Aug; 106(8): 1024–8PubMedCrossRefGoogle Scholar
  43. 43.
    McKenney JM, Davidson MH, Jacobson TA, et al. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol 2006 Apr; 97(8A): 89C–94CPubMedCrossRefGoogle Scholar
  44. 44.
    Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther 2006 Dec; 80(6): 565–81PubMedCrossRefGoogle Scholar
  45. 45.
    Davidson MH, Robinson JG. Safety of aggressive lipid management. J Am Coll Cardiol 2007 May; 49(17): 1753–62PubMedCrossRefGoogle Scholar
  46. 46.
    Brass LM, Alberts MJ, Sparks L. An assessment of statin safety by neurologists. Am J Cardiol 2006 Apr; 97(8A): 86C–8CPubMedCrossRefGoogle Scholar
  47. 47.
    National Cholesterol Education Program. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001 May; 285(19): 2486–97CrossRefGoogle Scholar
  48. 48.
    Davidson MH. The use of colesevelam hydrochloride in the treatment of dyslipidemia: a review. Expert Opin Pharmacother 2007 Oct; 8(15): 2569–78PubMedCrossRefGoogle Scholar
  49. 49.
    Jacobson TA, Armani A, McKenney JM, et al. Safety considerations with gastrointestinally active lipid-lowering drugs. Am J Cardiol 2007 Mar; 99(6A): 47C–55CPubMedCrossRefGoogle Scholar
  50. 50.
    Florentin M, Liberopoulos EN, Mikhailidis DP, et al. Colesevelam hydrochloride in clinical practice: a new approach in the treatment of hypercholesterolaemia. Curr Med Res Opin 2008 Apr; 24(4): 995–1009PubMedCrossRefGoogle Scholar
  51. 51.
    Welchol™ (colesevelam hydrochloride): US prescribing information. Parsippany (NJ): Daiichi Sankyo, 2008 [online]. Available from URL: http://www.welchol.com/pdf/Welchol_PI.pdf [Accessed 2010 Mar 19]
  52. 52.
    Pearson TA, Denke MA, McBride PE, et al. A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: the Ezetimibe Add-on to Statin for Effectiveness (EASE) trial. Mayo Clin Proc 2005 May; 80(5): 587–95PubMedCrossRefGoogle Scholar
  53. 53.
    Pearson T, Denke M, McBride P, et al. Effectiveness of the addition of ezetimibe to ongoing statin therapy in modifying lipid profiles and attaining low-density lipoprotein cholesterol goals in older and elderly patients: subanalyses of data from a randomized, double-blind, placebo-controlled trial. Am J Geriatr Pharmacother 2005 Dec; 3(4): 218–28PubMedCrossRefGoogle Scholar
  54. 54.
    Robinson JG, Davidson MH, Shah A, et al. Efficacy and safety of ezetimibe and ezetimibe plus statin therapy in patients aged under 65, 65–74 and 75 years and older. Aging Health 2007; 3: 691–705CrossRefGoogle Scholar
  55. 55.
    Kastelein JJP, Akdim F, Stroes ESG, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008 Apr; 358(14): 1431–43PubMedCrossRefGoogle Scholar
  56. 56.
    Fleg JL, Mete M, Howard BV, et al. Effect of statins alone versus statins plus ezetimibe on carotid atherosclerosis in type 2 diabetes: the SANDS (Stop Atherosclerosis in Native Diabetics Study) trial. J Am Coll Cardiol 2008 Dec; 52(25): 2198–205PubMedCrossRefGoogle Scholar
  57. 57.
    Cannon CP, Giugliano RP, Blazing MA, et al. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimibe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J 2008; 156(5): 826–32PubMedCrossRefGoogle Scholar
  58. 58.
    Califf RM, Lokhnygina Y, Cannon CP, et al. An update on the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) design. Am Heart J 2010 May; 159(5): 705–9PubMedCrossRefGoogle Scholar
  59. 59.
    Zetia® (ezetimibe): US prescribing information. North Wales (PA): Merck/Schering-Plough Pharmaceuticals, 2009 [online]. Available from URL:http://www.zetia.com/zetia/shared/documents/zetia_pi.pdf [Accessed 2010 Mar 19]
  60. 60.
    Kashani A, Sallam T, Bheemreddy S, et al. Review of side-effect profile of combination ezetimibe and statin therapy in randomized clinical trials. Am J Cardiol 2008 Jun; 101(11): 1606–13PubMedCrossRefGoogle Scholar
  61. 61.
    Davidson MH, Maccubbin D, Stepanavage M, et al. Striated muscle safety of ezetimibe/simvastatin (Vytorin). Am J Cardiol 2006 Jan; 97(2): 223–8PubMedCrossRefGoogle Scholar
  62. 62.
    Stein EA, Ballantyne CM, Windler E, et al. Efficacy and tolerability of fluvastatin XL 80 mg alone, ezetimibe alone, and the combination of fluvastatin XL 80 mg with ezetimibe in patients with a history of muscle-related side effects with other statins. Am J Cardiol 2008 Feb; 101(4): 490–6PubMedCrossRefGoogle Scholar
  63. 63.
    Feldman T, Davidson M, Shah A, et al. Low density lipoprotein lowering efficacy of the ezetimibe/simvastatin combination tablet in a large cohort of elderly patients with primary hypercholesterolemia [abstract]. J Am Geriatr Soc 2005; 53(4 Suppl.): S78–9Google Scholar
  64. 64.
    Abate N, Ballantyne CM, Catapano AL, et al. LDL-C lowering efficacy of the ezetimibe/simvastatin single tablet compared with atorvastatin or rosuvastatin in elderly patients with hypercholesterolemia [abstract]. J Am Geriatr Soc 2006; 54(4 Suppl.): S163Google Scholar
  65. 65.
    Rossebø AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008 Sep; 359(13): 1343–56PubMedCrossRefGoogle Scholar
  66. 66.
    Peto R, Emberson J, Landray M, et al. Analyses of cancer data from three ezetimibe trials. N Engl J Med 2008 Sep; 359(13): 1357–66PubMedCrossRefGoogle Scholar
  67. 67.
    SHARP Collaborative Group: Study of Heart and Renal Protection (SHARP). Randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease. Am Heart J. Epub 2010 Sep 20; doi: 10.1016/j.ahj.2010.08.012Google Scholar
  68. 68.
    Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol 1986 Dec; 8(6): 1245–55PubMedCrossRefGoogle Scholar
  69. 69.
    Berge KG, Canner PL. Coronary drug project: experience with niacin. Coronary Drug Project Research Group. Eur J Clin Pharmacol 1991; 40Suppl. 1: S49–51PubMedGoogle Scholar
  70. 70.
    McCormack PL, Keating GM. Prolonged-release nicotinic acid: a review of its use in the treatment of dyslipidaemia. Drugs 2005; 65(18): 2719–40PubMedCrossRefGoogle Scholar
  71. 71.
    Niaspan® (niacin extended-release tablets): US prescribing information. North Chicago (IL): Abbott Laboratories, 2009 [online]. Available from URL: http://www.rxabbott.com/pdf/niaspan.pdf [Accessed 2010 Mar 19]
  72. 72.
    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 Aug; 341(6): 410–8PubMedCrossRefGoogle Scholar
  73. 73.
    FIELD study investigators. 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 Nov; 366(9500): 1849–61CrossRefGoogle Scholar
  74. 74.
    Meade T, Zuhrie R, Cook C, et al. Bezafibrate in men with lower extremity arterial disease: randomised controlled trial. BMJ 2002 Nov; 325(7373): 1139PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Joseph E. Thomas
    • 1
  • Andrew M. Tershakovec
    • 2
  • Charlotte Jones-Burton
    • 3
  • Reza A. Sayeed
    • 4
  • JoAnne M. Foody
    • 5
  1. 1.Division of CardiologyUniversity of KentuckyLexingtonUSA
  2. 2.Clinical ResearchMerckNorth WalesUSA
  3. 3.Clinical ResearchMerckRahwayUSA
  4. 4.Bioscript Stirling LtdLondonUK
  5. 5.Brigham and Women’s HospitalBostonUSA

Personalised recommendations