Rational Pharmacotherapy in Cardiology

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Effect of hyperlipidemia on morbidity and mortality in elderly patients is considered. Authors also cover issues of efficacy and safety of lipid-lowering therapy in primary and secondary prevention of cardiovascular diseases in patients ≥80 years of age who are the most quickly growing group of population and have the highest cardiovascular risk. They stress the need to take into account polymorbidity and polypharmacy that increase the risk of adverse reactions due to the use of both statins and their drug-drug interactions, which requires an assessment of risk/benefit ratio. In addition, there is a need for development of reliable prognostic tools to predict relevant outcomes (e.g., stroke, decrease in functionality/independence, quality of life reduction) and rationales for lipid-lowering therapy in the elderly and also their adherence to treatment.

About the Authors

E. A. Ushkalova
Russian University of Peoples' Friendship. Mikluho-Maclaya ul. 6, Moscow, 6117198 Russia
Russian Federation

O. N. Tkacheva
Russian Gerontological Research and Clinical Center. Pervaya Leonova ul. 16, Moscow, 129226 Russia
Russian Federation

N. K. Runikhina
Russian Gerontological Research and Clinical Center. Pervaya Leonova ul. 16, Moscow, 129226 Russia
Russian Federation

N. A. Chukhareva
Scientific Center for Obstetrics, Gynecology and Perinatology named after academician V.I. Kulakov. Oparina ul. 4, Moscow, 117997 Russia
Russian Federation

A. Yu. Bevz
Russian Gerontological Research and Clinical Center. Pervaya Leonova ul. 16, Moscow, 129226 Russia
Russian Federation


1. World Health Organization. Global status report on noncommunicable diseases. WHO: Geneva; 2010.

2. Hamilton-Craig I, Colquhoun D, Kostner K, et al. Lipid-modifying therapy in the elderly. Vasc Health Risk Manag 2015;11:251-63.

3. Mozaffarian D, Benjamin EJ, Go AS, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics—2015 Update: a report from the American Heart Association. Circulation 2015;131: e29-e322.

4. Jacobson TA, Maki KC, Orringer CE3, et al. National Lipid Association Recommendations for PatientCentered Management of Dyslipidemia: Part 2. J Clin Lipidol 2015;9(6 Suppl):S1-122e1.

5. Alpérovitch A, Kurth T, Bertrand M, et al. Primary prevention with lipid lowering drugs and long term risk of vascular events in older people: population based cohort study. BMJ 2015;350:h2335.

6. Kannel WB. Coronary heart disease risk factors in the elderly. Am J Geriatr Cardiol 2002;11(2): 101-107.

7. Petersen LK, Christensen K, Kragstrup J. Lipid-lowering treatment to the end? A review of observational studies and RCTs on cholesterol and mortality in 80+-year olds. Age Ageing 2010;39(6):674-80.

8. Iversen A1, Jensen JS, Scharling H, Schnohr P. Hypercholesterolaemia and risk of coronary heart disease in the elderly: impact of age: the Copenhagen City Heart Study. Eur J Intern Med 2009;20(2): 139-44.

9. Abdelhafiz AH, Loo BE, Hensey N, et al. The U-shaped Relationship of Traditional Cardiovascular Risk Factors and Adverse Outcomes in Later Life. Aging Dis 2012;3(6):454-64.

10. Newson RS, Felix JF, Heeringa J, et al. Association between serum cholesterol and noncardiovascular mortality in older age. J Am Geriatr Soc 2011;59(10):1779-85.

11. Anum EA, Adera T. Hypercholesterolemia and coronary heart disease in the elderly: a meta-analysis. Ann Epidemiol 2004;14(9):705-21.

12. Prospective Studies Collaboration, Lewington S, Whitlock G, Clarke R, et al. 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 1;370(9602):1829-39.

13. DuBroff R, de Lorgeril M. Cholesterol confusion and statin controversy. World J Cardiol. 2015 Jul 26;7(7):404-9.

14. Jacobson TA, Maki KC, Orringer CE, et al. National Lipid Association Recommendations for PatientCentered Management of Dyslipidemia: Part 2. Clin Lipidol. 2015 Nov-Dec;9(6 Suppl):S1-122.

15. Roberts CG, Guallar E, Rodriguez A. Efficacy and safety of statin monotherapy in older adults: a metaanalysis. J Gerontol A Biol Sci Med Sci. 2007;62:879-887.

16. Wei MY, Ito MK, Cohen JD, et al. Predictors of statin adherence, switching, and discontinuation in the USAGE survey: understanding the use of statins in America and gaps in patient education. J Clin Lipidol. 2013 Sep-Oct;7(5):472-83.

17. Macedo AF, Taylor FC, Casas JP, Adler A, Prieto-Merino D, Ebrahim S. Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis. BMC Med. 2014;12:51.

18. Sathasivam S. Statin induced myotoxicity. Eur J Intern Med 2012;23:317-24.

19. Gaist D, Rodriquez LA, Huerta C, et al. Lipidlowering drugs and risk of myopathy: a population-based follow-up study. Epidemiology. 2001;12:565-569.

20. Ito MK, Maki KC, Brinton EA, Cohen JD, Jacobson TA. Muscle symptoms in statin users, associations with cytochrome P450, and membrane transporter inhibitor use: a subanalysis of the USAGE study. J Clin Lipidol. 2014;8:69-76.

21. Kellick KA, Bottorff M, Toth PP, The National Lipid Association’s Safety Task Force. A clinician’s guide to statin drug-drug interactions.J Clin Lipidol. 2014;8(3 Suppl):S30-S46.

22. Hobbs FD1, Banach M2, Mikhailidis DP, et al. Is statin-modified reduction in lipids the most important preventive therapy for cardiovascular disease? A pro/con debate. BMC Med. 2016 Jan 14;14:4.

23. Fleg JL, Forman DE, Berra K, et al. American Heart Association Committees on Older Populations and Exercise Cardiac Rehabilitation and Prevention of Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing, Council on Lifestyle and Cardiometabolic Health. Secondary prevention of atherosclerotic cardiovascular disease in older adults: a scientific statement from the AmericanHeart Association. Circulation. 2013;128:2422-2446.

24. Ray KK, Bach RG, Cannon CP, et al. Benefits of achieving the NCEP optional LDL-C goal among elderly patients with ACS. Eur Heart J. 2006;27:2310-2316.

25. Wenger NK, Lewis SJ, Herrington DM, et al. Outcomes of using high- or low-dose atorvastatin in patients 65 years of age or older with stable coronary heart disease. Ann Intern Med. 2007;147:1-9.

26. Deedwania P, Stone PH, Bairey Merz CN, et al. Effects of intensive versus moderate lipidlowering therapy on myocardial ischemia in older patients with coronary heart disease:results of the Study Assessing Goals in the Elderly (SAGE). Circulation. 2007;115:700-707.

27. Finegold JA, Manisty CH, Goldacre B, Barron AJ, Francis DP. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice. Eur J Prev Cardiol. 2014;21(4):464-74.

28. Park ZH, Juska A, Dyakov D, Patel RV. Statin-associated incident diabetes: a literature review. Consult Pharm. 2014;29(5):317-34.

29. van de Woestijne AP, van der Graaf Y, Westerink J, et al. Effect of statin therapy on incident type 2 diabetes mellitus in patients with clinically manifest vascular disease. Am J Cardiol. 2015 Feb 15;115(4):441-6.

30. Plakogiannis R, Arif SA.Women Versus Men: Is There Equal Benefit and Safety from Statins? Curr Atheroscler Rep. 2016 Feb;18(2):6.

31. Wong WB, Lin VW, Boudreau D, Devine EB. Statins in the prevention of dementia and Alzheimer’s disease: a meta-analysis of observational studies and an assessment of confounding. Pharmacoepidemiol Drug Saf. 2013;22(4):345-358.

32. Gnjidic D, Fastbom J, Fratiglioni L, et al. Statin Therapy and Dementia in Older Adults: Role of Disease Severity and Multimorbidity. J Am Geriatr Soc. 2016 Jan;64(1):223-4.

33. McGuinness B, Craig D, Bullock R, Passmore P. Statins for the prevention of dementia. Cochrane Database Syst Rev. 2016 Jan 4;1:CD003160

34. Muangpaisan W, Brayne C; Alzheimer’s Society Vascular Dementia Systematic Review Group . Systematic review of statins for the prevention of vascular dementia or dementia. Geriatr Gerontol Int. 2010;10(2):199-20.

35. Ito MK. Dyslipidemia: Management Using Optimal Lipid-Lowering Therapy. Ann Pharmacother 2012;46:1368-81.

36. U.S. Food andDrug Administration (FDA). FDA Safety Communication: Important safety label changes to cholesterol-lowering statin drugs [2-28-2012]. ucm293101.htm.

37. Shepherd J, Blauw GJ, Murphy MB, et al. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623-1630.

38. Heart Protection Study Collaborative Group. 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.

39. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670-1681.

40. Zhou YY, Zhu GQ, Wang Y, et al. Systematic review with network meta-analysis: statins and risk of hepatocellular carcinoma. Oncotarget. 2016 Mar 1. doi: 10.18632/oncotarget.7832. [Epub ahead of print]

41. Ananthakrishnan AN, Cagan A, Cai T, et al. Statin Use Is Associated With Reduced Risk of Colorectal Cancer in Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol. 2016 Feb 22 [Epub ahead of print],

42. Zhong S, Zhang X, Chen L, et al. Statin use and mortality in cancer patients: Systematic review and meta-analysis of observational studies. Cancer Treat Rev. 2015 Jun;41(6):554-67.

43. Raval AD, Thakker D, Negi H, et al. Association between statins and clinical outcomes among men with prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2016 Jan 19. [Epub ahead of print].

44. Mansourian M1, Haghjooy-Javanmard S, Eshraghi A, et al. Statins Use and Risk of Breast Cancer Recurrence and Death: A Systematic Review and Meta-Analysis of Observational Studies.J Pharm Pharm Sci. 2016 Jan-Mar;19(1):72-81.

45. Jansen PA, Brouwers JR. Сlinical pharmacology in old persons. Scientifica (Cairo). 2012;2012:723678

46. Lloyd SM, Stott DJ, de Craen AJ, et al. Long-term effects of statin treatment in elderly people: extended follow-up of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). PLoS One. 2013 Sep 2;8(9):e72642.

47. Heart Protection Study Collaborative Group (2011) Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20 536 high-risk individuals: A randomised controlled trial. Lancet 378; 2013-20.

48. Afilalo J, Duque G, Steele R, Jukema JW, de Craen AJ, Eisenberg MJ. Statins for secondary prevention in elderly patients: a hierarchical bayesian meta-analysis. J Am Coll Cardiol. 2008;51:37-45.

49. Jacobson TA. NLATask Force on Statin Safety - 2014 update. J Clin Lipidol. 2014;8(3 Suppl):S1-S4.

50. Allen Maycock CA, Muhlestein JB, Horne BD, et al. Statin therapy is associated with reduced mortality across all age groups of individuals with significant coronary disease, including very elderly patients. J Am Coll Cardiol. 2002 Nov 20;40(10):1777-85.

51. Fleg JL, Aronow WS, Frishman WH. Cardiovascular drug therapy in the elderly: benefits and challenges. Nat Rev Cardiol. 2011;8:13-28.

52. 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;96:4211-4218.

53. Lewis SJ, Sacks FM, Mitchell JS, et al. Effect of pravastatin on cardiovascular events in women after myocardial infarction: the Cholesterol and Recurrent Events (CARE) trial. J Am Coll Cardiol. 1998; 32: 140-146.

54. 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.134, 931-940 (2001).

55. Wenger NK, Lewis SJ,HerringtonDM, Bittner V, Welty FK; Treating to New Targets Study Steering Committee and Investigators. Outcomes of using high- or low-dose atorvastatin in patients 65 years of age or older with stable coronary heart disease. Ann Intern Med. 2007;147:1-9.

56. Olsson AG, Schwartz GG, Szarek M, et al. Effects of high-dose atorvastatin in patients > or =65 years of age with acute coronary syndrome (from the myocardial ischemia reduction with aggressive cholesterol lowering [MIRACL] study). Am. J. Cardiol. 99, 632-635 (2007).

57. Ray KK, Bach RG, Cannon CP, Cairns R, Kirtane AJ, Wiviott SD, McCabe CH, Braunwald E, Gibson CM; PROVE IT-TIMI 22 Investigators. Benefits of achieving the NCEP optional LDL-C goal among elderly patients with ACS. Eur Heart J. 2006;27:2310-2316.

58. O'MahonyD, O'SullivanD, Byrne S, et al. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing. 2015 Mar;44(2):213-8.

59. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2889-2934.

60. Anderson TJ, Gregoire J, Hegele RA, et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2013;29:151-167.

61. National Institute for Health and Care Excellence. Lipid modification. Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. Clinical guideline. Methods, evidence and recommendations. July 2014 243786637

62. European Association for Cardiovascular Prevention & Rehabilitation1, Reiner Z, Catapano AL, et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011 Jul;32(14):1769-818.

63. Национальное Общество по изучению Атеросклероза (НОА), Российское кардиологическое об- щество (РКО), Российское общество кардиосоматической реабилитации и вторичной профи- лактики (РосОКР).Диагностика и коррекция нарушений липидного обмена с целью профилактики и лечения атеросклероза/Российские рекомендации. V пересмотр. Москва. 2012 год.

64. Boden WE, Probstfield JL, Anderson T, Chaitman BR. Niacin in patients with low hdl cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255-67.

65. Al-Hijji, M., Martin SS, Joshi PH, Jones SR. Effect of equivalent on-treatment apolipoprotein levels on outcomes (from the AIM-HIGH and HPS2-THRIVE). Am J Cardiol, 2013. 112(10): p. 1697-700.

66. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015 Jun 18;372(25):2387-97.

67. Bohula EA, Giugliano RP, Cannon CP, et al. Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better better outcomes in IMPROVE-IT. Circulation. 2015 Sep 29;132(13):1224-33.

68. 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;3:218-228.

69. Savarese G, Gotto AM Jr, Paolillo S, et al. Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis. J Am Coll Cardiol. 2013 Dec 3;62(22):2090-9.

70. Teng M, Lin L, Zhao YJ, et al. Statins for Primary Prevention of Cardiovascular Disease in Elderly Patients: Systematic Review and Meta-Analysis. Drugs Aging. 2015 Aug;32(8):649-61.

For citation:

Ushkalova E.A., Tkacheva O.N., Runikhina N.K., Chukhareva N.A., Bevz A.Y. EFFICACY AND SAFETY OF LIPID-LOWERING DRUGS IN PRIMARY AND SECONDARY PREVENTION OF CARDIOVASCULAR DISEASES IN THE ELDERLY. Rational Pharmacotherapy in Cardiology. 2016;12(3):351-358.

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