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Drug Therapy of Dyslipidemia in the Elderly

  • Srikanth Yandrapalli
  • Shashvat Gupta
  • Gabriela Andries
  • Howard A. Cooper
  • Wilbert S. Aronow
Review Article
  • 61 Downloads

Abstract

Abnormal lipoprotein metabolism is an important and modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD), which has been shown in numerous studies to lead to adverse cardiovascular outcomes. As cardiovascular disease (CVD) remains the major cause of morbidity and mortality globally, management of dyslipidemia is a key component of primary and secondary risk-reduction strategies. Because ASCVD risk increases with age, as the population ages, many more people—particularly the elderly—will meet guideline criteria for drug treatment. Statins (HMG-CoA reductase inhibitors) have an unequivocal benefit in reducing ASCVD risk across age groups for secondary prevention. However, the benefit of these drugs for primary prevention in those > 75 years of age remains controversial. We strongly believe that statins should be offered for primary prevention to all older individuals after a shared decision-making process that takes polypharmacy, frailty, and potential adverse effects into consideration. When considering statin therapy in the very old, competing risks of death, and therefore the likelihood that patients will live long enough to benefit from drug therapy, should inform this process. Combination therapies with ezetimibe or proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors should be considered to facilitate the use of tolerable doses of statins. Future investigations of dyslipidemia therapies must appropriately include this at-risk population to identify optimal drugs and drug combinations that have a high benefit:risk ratio for the prevention of ASCVD in the elderly.

Notes

Compliance with Ethical Standards

Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

Srikanth Yandrapalli, Shashvat Gupta, Gabriela Andries, Howard A. Cooper, and Wilbert S. Aronow declare that they have no potential conflicts of interest that might be relevant to the contents of this review.

References

  1. 1.
    European Association for Cardiovascular Prevention & Rehabilitation, Reiner Z, Catapano AL, De Backer G, et al. ESC Committee for Practice Guidelines (CPG) 2008–2010 and 2010–2012 Committees 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;32(14):1769–818.  https://doi.org/10.1093/eurheartj/ehr158.CrossRefGoogle Scholar
  2. 2.
    Yusuf S, Hawken S, Ounpuu S, INTERHEART Study Investigators, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):937–52.  https://doi.org/10.1016/S0140-6736(04)17018-9.CrossRefPubMedGoogle Scholar
  3. 3.
    Psaty BM, Anderson M, Kronmal RA, et al. The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: the Cardiovascular Health Study. J Am Geriatr Soc. 2004;52(10):1639–47.  https://doi.org/10.1111/j.1532-5415.2004.52455.x.CrossRefPubMedGoogle Scholar
  4. 4.
    Reina SA, Llabre MM, Allison MA, et al. HDL cholesterol and stroke risk: the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2015;243(1):314–9.  https://doi.org/10.1016/j.atherosclerosis.2015.09.031.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Mackey RH, Greenland P, Goff DC, Lloyd-Jones D, Sibley CT, Mora S. High-density lipoprotein cholesterol and particle concentrations, carotid atherosclerosis, and coronary events: MESA (multi-ethnic study of atherosclerosis). J Am Coll Cardiol. 2012;60(6):508–16.  https://doi.org/10.1016/j.jacc.2012.03.060.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Tsimikas S, Brilakis ES, Miller ER, et al. Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease. N Engl J Med. 2005;353(1):46–57.  https://doi.org/10.1056/NEJMoa043175.CrossRefPubMedGoogle Scholar
  7. 7.
    Rosenson RS. Statins in atherosclerosis: lipid-lowering agents with antioxidant capabilities. Atherosclerosis. 2004;173(1):1–12.  https://doi.org/10.1016/S0021-9150(03)00239-9.CrossRefPubMedGoogle Scholar
  8. 8.
    Castelli WP, Anderson K, Wilson PW, Levy D. Lipids and risk of coronary heart disease. The Framingham Study. Ann Epidemiol. 1992;2(1–2):23–8.CrossRefPubMedGoogle Scholar
  9. 9.
    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(25 Pt B):2889–934.  https://doi.org/10.1016/j.jacc.2013.11.002.CrossRefPubMedGoogle Scholar
  10. 10.
    Wadhera RK, Steen DL, Khan I, Giugliano RP, Foody JM. A review of low-density lipoprotein cholesterol, treatment strategies, and its impact on cardiovascular disease morbidity and mortality. J Clin Lipidol. 2016;10(3):472–89.  https://doi.org/10.1016/j.jacl.2015.11.010.CrossRefPubMedGoogle Scholar
  11. 11.
    Wilson PWF, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97(18):1837–47.  https://doi.org/10.1161/01.CIR.97.18.1837.CrossRefPubMedGoogle Scholar
  12. 12.
    Sharrett AR, Ballantyne CM, Coady SA, et al. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2001;104(10):1108–13.CrossRefPubMedGoogle Scholar
  13. 13.
    Abdalamir M, Goyfman M, Chaus A, et al. The correlation of dyslipidemia with the extent of coronary artery disease in the multiethnic study of atherosclerosis. J Lipids. 2018.  https://doi.org/10.1155/2018/5607349.CrossRefGoogle Scholar
  14. 14.
    Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37(39):2999–3058.  https://doi.org/10.1093/eurheartj/ehw272.CrossRefPubMedGoogle Scholar
  15. 15.
    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(9493):1267–78.  https://doi.org/10.1016/S0140-6736(05)67394-1.CrossRefPubMedGoogle Scholar
  16. 16.
    Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, 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(9753):1670–81.  https://doi.org/10.1016/S0140-6736(10)61350-5.CrossRefGoogle Scholar
  17. 17.
    Silverman MG, Ference BA, Im K, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA. 2016;316(12):1289–97.  https://doi.org/10.1001/jama.2016.13985.CrossRefPubMedGoogle Scholar
  18. 18.
    Cholesterol Treatment Trialists’ (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380(9841):581–90.  https://doi.org/10.1016/S0140-6736(12)60367-5.CrossRefGoogle Scholar
  19. 19.
    Sabatine MS, Wiviott SD, Im K, Murphy SA, Giugliano RP. Efficacy and safety of further lowering of low-density lipoprotein cholesterol in patients starting with very low levels: a meta-analysis. JAMA Cardiol. 2018;3(9):823–8.  https://doi.org/10.1001/jamacardio.2018.2258.CrossRefPubMedGoogle Scholar
  20. 20.
    Navarese EP, Robinson JG, Kowalewski M, et al. Association between baseline LDL-C level and total and cardiovascular mortality after LDL-c lowering: a systematic review and meta-analysis. JAMA. 2018;319(15):1566–79.  https://doi.org/10.1001/jama.2018.2525.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Halcox JP, Banegas JR, Roy C, et al. Prevalence and treatment of atherogenic dyslipidemia in the primary prevention of cardiovascular disease in Europe: EURIKA, a cross-sectional observational study. BMC Cardiovasc Disord. 2017;17(1):160.  https://doi.org/10.1186/s12872-017-0591-5.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Steinhagen-Thiessen E, Bramlage P, Lösch C, et al. Dyslipidemia in primary care—prevalence, recognition, treatment and control: data from the German Metabolic and Cardiovascular Risk Project (GEMCAS). Cardiovasc Diabetol. 2008;7:31.  https://doi.org/10.1186/1475-2840-7-31.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Lin C-F, Chang Y-H, Chien S-C, Lin Y-H, Yeh H-Y. Epidemiology of dyslipidemia in the Asia Pacific region. Int J Gerontol. 2018;12(1):2–6.  https://doi.org/10.1016/j.ijge.2018.02.010.CrossRefGoogle Scholar
  24. 24.
    Pan L, Yang Z, Wu Y, et al. The prevalence, awareness, treatment and control of dyslipidemia among adults in China. Atherosclerosis. 2016;248:2–9.  https://doi.org/10.1016/j.atherosclerosis.2016.02.006.CrossRefPubMedGoogle Scholar
  25. 25.
    Reiner Ž, Tedeschi-Reiner E. Prevalence and types of persistent dyslipidemia in patients treated with statins. Croat Med J. 2013;54(4):339–45.  https://doi.org/10.3325/cmj.2013.54.339.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    CDC. High cholesterol facts. Centers for Disease Control and Prevention; 2017. https://www.cdc.gov/cholesterol/facts.htm. Accessed 12 Sep 2018.
  27. 27.
    Benjamin EJ, Virani SS, Callaway CW, et al. Heart Disease and stroke statistics—2018 update: a report from the American Heart Association. Circulation. 2018;137(12):e67–492.  https://doi.org/10.1161/CIR.0000000000000558.CrossRefPubMedGoogle Scholar
  28. 28.
    WHO. World health statistics 2018: monitoring health for the SDGs. WHO. http://www.who.int/gho/publications/world_health_statistics/2018/en/. Accessed 12 Sep 2018.
  29. 29.
    WHO. Proposed working definition of an older person in Africa for the MDS Project; WHO. http://www.who.int/healthinfo/survey/ageingdefnolder/en/. Accessed 12 Sep 2018.
  30. 30.
    Yazdanyar A, Newman AB. The burden of cardiovascular disease in the elderly: morbidity, mortality, and costs. Clin Geriatr Med. 2009;25(4):563–577, vii.  https://doi.org/10.1016/j.cger.2009.07.007.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Aronow WS. Lipid-lowering therapy in older persons. Arch Med Sci. 2015;11(1):43–56.  https://doi.org/10.5114/aoms.2015.48148.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38–360.  https://doi.org/10.1161/CIR.0000000000000350.CrossRefPubMedGoogle Scholar
  33. 33.
    Jacobson TA, Maki KC, Orringer CE, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 2. J Clin Lipidol. 2015;9(6):S1–S122.e1.  https://doi.org/10.1016/j.jacl.2015.09.002.CrossRefPubMedGoogle Scholar
  34. 34.
    Marrugat J, Sala J, Manresa JM, et al. Acute myocardial infarction population incidence and in-hospital management factors associated to 28-day case-fatality in the 65 year and older. Eur J Epidemiol. 2004;19(3):231–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Kayani WT, Ballantyne CM. Improving outcomes after myocardial infarction in the US population. J Am Heart Assoc. 2018;7(4):e008407.  https://doi.org/10.1161/JAHA.117.008407.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Schaefer EJ, Lamon-Fava S, Cohn SD, et al. Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study. J Lipid Res. 1994;35(5):779–92.PubMedGoogle Scholar
  37. 37.
    Ericsson S, Eriksson M, Vitols S, Einarsson K, Berglund L, Angelin B. Influence of age on the metabolism of plasma low density lipoproteins in healthy males. J Clin Investig. 1991;87(2):591–6.  https://doi.org/10.1172/JCI115034.CrossRefPubMedGoogle Scholar
  38. 38.
    Schatz IJ, Masaki K, Yano K, Chen R, Rodriguez BL, Curb JD. Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study. Lancet. 2001;358(9279):351–5.  https://doi.org/10.1016/S0140-6736(01)05553-2.CrossRefPubMedGoogle Scholar
  39. 39.
    Shanmugasundaram M, Rough SJ, Alpert JS. Dyslipidemia in the elderly: should it be treated? Clin Cardiol. 2010;33(1):4–9.  https://doi.org/10.1002/clc.20702.CrossRefPubMedGoogle Scholar
  40. 40.
    Castelli WP, Wilson PWF, Levy D, Anderson K. Cardiovascular risk factors in the elderly. Am J Cardiol. 1989;63(16):12–9.  https://doi.org/10.1016/0002-9149(89)90110-0.CrossRefGoogle Scholar
  41. 41.
    Rubin SM, Sidney S, Black DM, Browner WS, Hulley SB, Cummings SR. High blood cholesterol in elderly men and the excess risk for coronary heart disease. Ann Intern Med. 1990;113(12):916–20.CrossRefPubMedGoogle Scholar
  42. 42.
    Aslam F, Haque A, Lee LV, Foody J. Hyperlipidemia in older adults. Clin Geriatr Med. 2009;25(4):591–606.  https://doi.org/10.1016/j.cger.2009.08.001.CrossRefPubMedGoogle Scholar
  43. 43.
    Wong ND, Wilson PW, Kannel WB. Serum cholesterol as a prognostic factor after myocardial infarction: the Framingham Study. Ann Intern Med. 1991;115(9):687–93.CrossRefPubMedGoogle Scholar
  44. 44.
    Aronow WS, Ahn C. Risk factors for new coronary events in a large cohort of very elderly patients with and without coronary artery disease. Am J Cardiol. 1996;77(10):864–6.  https://doi.org/10.1016/S0002-9149(97)89183-7.CrossRefPubMedGoogle Scholar
  45. 45.
    Suryadevara V, Storey SG, Aronow WS, Ahn C. Association of abnormal serum lipids in elderly persons with atherosclerotic vascular disease and dementia, atherosclerotic vascular disease without dementia, dementia without atherosclerotic vascular disease, and no dementia or atherosclerotic vascular disease. J Gerontol A Biol Sci Med Sci. 2003;58(9):M859–61.CrossRefPubMedGoogle Scholar
  46. 46.
    Aronow WS, Ahn C. Correlation of serum lipids with the presence or absence of coronary artery disease in 1,793 men and women aged > or = 62 years. Am J Cardiol. 1994;73(9):702–3.CrossRefPubMedGoogle Scholar
  47. 47.
    Aronow WS, Frishman WH. Management of hypercholesterolemia in older persons for the prevention of cardiovascular disease. Cardiol Rev. 2010;18(3):132–40.  https://doi.org/10.1097/CRD.0b013e3181c29571.CrossRefPubMedGoogle Scholar
  48. 48.
    Aronow WS, Sales FF, Etienne F, Lee NH. Prevalence of peripheral arterial disease and its correlation with risk factors for peripheral arterial disease in elderly patients in a long-term health care facility. Am J Cardiol. 1988;62(9):644–6.CrossRefPubMedGoogle Scholar
  49. 49.
    Aronow WS, Ahn C. Correlation of serum lipids with the presence or absence of atherothrombotic brain infarction and peripheral arterial disease in 1,834 men and women aged ≥ 62 years. Am J Cardiol. 1994;73(13):995–7.  https://doi.org/10.1016/0002-9149(94)90154-6.CrossRefPubMedGoogle Scholar
  50. 50.
    Zimetbaum P, Frishman WH, Ooi WL, et al. Plasma lipids and lipoproteins and the incidence of cardiovascular disease in the very elderly. The Bronx Aging Study. Arterioscler Thromb J Vasc Biol. 1992;12(4):416–23.CrossRefGoogle Scholar
  51. 51.
    Prospective Studies Collaboration, Lewington S, Whitlock G, 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;370(9602):1829–39.  https://doi.org/10.1016/S0140-6736(07)61778-4.CrossRefGoogle Scholar
  52. 52.
    Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian Cardiovascular Society Guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2016;32(11):1263–82.  https://doi.org/10.1016/j.cjca.2016.07.510.CrossRefPubMedGoogle Scholar
  53. 53.
    Wierzbicki AS, Poston R, Ferro A. The lipid and non-lipid effects of statins. Pharmacol Ther. 2003;99(1):95–112.CrossRefPubMedGoogle Scholar
  54. 54.
    Miettinen TA, Pyörälä 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(12):4211–8.CrossRefPubMedGoogle Scholar
  55. 55.
    Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344(8934):1383–9.Google Scholar
  56. 56.
    Pedersen TR, Kjekshus J, Pyörälä K, et al. Effect of simvastatin on ischemic signs and symptoms in the Scandinavian simvastatin survival study (4S). Am J Cardiol. 1998;81(3):333–5.CrossRefPubMedGoogle Scholar
  57. 57.
    Pedersen TR, Wilhelmsen L, Faergeman O, et al. Follow-up study of patients randomized in the Scandinavian simvastatin survival study (4S) of cholesterol lowering. Am J Cardiol. 2000;86(3):257–62.CrossRefPubMedGoogle Scholar
  58. 58.
    Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335(14):1001–9.  https://doi.org/10.1056/NEJM199610033351401.CrossRefPubMedGoogle Scholar
  59. 59.
    Lewis SJ, Moye LA, Sacks FM, et al. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) trial. Ann Intern Med. 1998;129(9):681–9.CrossRefPubMedGoogle Scholar
  60. 60.
    Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339(19):1349–57.  https://doi.org/10.1056/NEJM199811053391902.CrossRefGoogle Scholar
  61. 61.
    LIPID Study Group (Long-term Intervention with Pravastatin in Ischaemic Disease). Long-term effectiveness and safety of pravastatin in 9014 patients with coronary heart disease and average cholesterol concentrations: the LIPID trial follow-up. Lancet. 2002;359(9315):1379–87.  https://doi.org/10.1016/S0140-6736(02)08351-4.CrossRefGoogle Scholar
  62. 62.
    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(9326):7–22.  https://doi.org/10.1016/S0140-6736(02)09327-3.CrossRefGoogle Scholar
  63. 63.
    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(13):1711–8.CrossRefPubMedGoogle Scholar
  64. 64.
    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(15):1495–504.  https://doi.org/10.1056/NEJMoa040583.CrossRefPubMedGoogle Scholar
  65. 65.
    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(19):2310–6.  https://doi.org/10.1093/eurheartj/ehl180.CrossRefPubMedGoogle Scholar
  66. 66.
    LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425–35.  https://doi.org/10.1056/NEJMoa050461.CrossRefPubMedGoogle Scholar
  67. 67.
    Wenger NK, Lewis SJ, Herrington DM, 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):1–9.CrossRefPubMedGoogle Scholar
  68. 68.
    Amarenco P, Bogousslavsky J, Callahan A, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549–59.  https://doi.org/10.1056/NEJMoa061894.CrossRefPubMedGoogle Scholar
  69. 69.
    Chaturvedi S, Zivin J, Breazna A, et al. Effect of atorvastatin in elderly patients with a recent stroke or transient ischemic attack. Neurology. 2009;72(8):688–94.  https://doi.org/10.1212/01.wnl.0000327339.55844.1a.CrossRefPubMedGoogle Scholar
  70. 70.
    Pedersen TR, Faergeman O, Kastelein JJP, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294(19):2437–45.  https://doi.org/10.1001/jama.294.19.2437.CrossRefPubMedGoogle Scholar
  71. 71.
    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(9346):1623–30.CrossRefPubMedGoogle Scholar
  72. 72.
    Packard CJ, Ford I, Robertson M, et al. Plasma lipoproteins and apolipoproteins as predictors of cardiovascular risk and treatment benefit in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Circulation. 2005;112(20):3058–65.  https://doi.org/10.1161/CIRCULATIONAHA.104.526848.CrossRefPubMedGoogle Scholar
  73. 73.
    Deedwania P, Stone PH, Bairey Merz CN, et al. Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE). Circulation. 2007;115(6):700–7.  https://doi.org/10.1161/CIRCULATIONAHA.106.654756.CrossRefPubMedGoogle Scholar
  74. 74.
    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;134(10):931–40.CrossRefPubMedGoogle Scholar
  75. 75.
    Aronow WS, Nayak D, Woodworth S, Ahn C. Effect of simvastatin versus placebo on treadmill exercise time until the onset of intermittent claudication in older patients with peripheral arterial disease at six months and at one year after treatment. Am J Cardiol. 2003;92(6):711–2.CrossRefPubMedGoogle Scholar
  76. 76.
    Mohler ER, Hiatt WR, Creager MA. Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease. Circulation. 2003;108(12):1481–6.  https://doi.org/10.1161/01.CIR.0000090686.57897.F5.CrossRefPubMedGoogle Scholar
  77. 77.
    Mondillo S, Ballo P, Barbati R, et al. Effects of simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease. Am J Med. 2003;114(5):359–64.CrossRefPubMedGoogle Scholar
  78. 78.
    Cholesterol Treatment Trialists’ (CTT) Collaborators, Kearney PM, Blackwell L, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371(9607):117–25.  https://doi.org/10.1016/S0140-6736(08)60104-X.CrossRefGoogle Scholar
  79. 79.
    Afilalo J, Duque G, Steele R, Jukema JW, de Craen AJM, Eisenberg MJ. Statins for secondary prevention in elderly patients: a hierarchical Bayesian meta-analysis. J Am Coll Cardiol. 2008;51(1):37–45.  https://doi.org/10.1016/j.jacc.2007.06.063.CrossRefPubMedGoogle Scholar
  80. 80.
    Aronow WS, Ahn C. Incidence of new coronary events in older persons with prior myocardial infarction and serum low-density lipoprotein cholesterol > or = 125 mg/dl treated with statins versus no lipid-lowering drug. Am J Cardiol. 2002;89(1):67–9.CrossRefPubMedGoogle Scholar
  81. 81.
    Aronow WS, Ahn C, Gutstein H. Incidence of new atherothrombotic brain infarction in older persons with prior myocardial infarction and serum low-density lipoprotein cholesterol > or =125 mg/dl treated with statins versus no lipid-lowering drug. J Gerontol A Biol Sci Med Sci. 2002;57(5):M333–5.CrossRefPubMedGoogle Scholar
  82. 82.
    Aronow WS, Ahn C. Frequency of congestive heart failure in older persons with prior myocardial infarction and serum low-density lipoprotein cholesterol > or = 125 mg/dl treated with statins versus no lipid-lowering drug. Am J Cardiol. 2002;90(2):147–9.CrossRefPubMedGoogle Scholar
  83. 83.
    Aronow WS, Ahn C, Gutstein H. Reduction of new coronary events and new atherothrombotic brain infarction in older persons with diabetes mellitus, prior myocardial infarction, and serum low-density lipoprotein cholesterol ≥125 mg/dl treated with statins. J Gerontol Ser A. 2002;57(11):M747–50.  https://doi.org/10.1093/gerona/57.11.M747.CrossRefGoogle Scholar
  84. 84.
    Aronow WS, Ahn C. Frequency of new coronary events in older persons with peripheral arterial disease and serum low-density lipoprotein cholesterol > or = 125 mg/dl treated with statins versus no lipid-lowering drug. Am J Cardiol. 2002;90(7):789–91.CrossRefPubMedGoogle Scholar
  85. 85.
    Aronow WS, Ahn C, Kronzon I, Goldman ME. Association of coronary risk factors and use of statins with progression of mild valvular aortic stenosis in older persons. Am J Cardiol. 2001;88(6):693–5.CrossRefPubMedGoogle Scholar
  86. 86.
    Ravipati G, Aronow WS, Ahn C, Channamsetty V, Sekhri V. Incidence of new stroke or new myocardial infarction or death in patients with severe carotid arterial disease treated with and without statins. Am J Cardiol. 2006;98(9):1170–1.  https://doi.org/10.1016/j.amjcard.2006.06.009.CrossRefPubMedGoogle Scholar
  87. 87.
    Ravipati G, Aronow WS, Kumbar S, et al. Patients with diabetes mellitus with ischemic stroke have a higher hemoglobin A1c level and a higher serum low-density lipoprotein cholesterol level than diabetics without ischemic stroke. Arch Med Sci. 2009;5(3):391–3.Google Scholar
  88. 88.
    Sukhija R, Aronow WS, Sandhu R, Kakar P, Babu S. Mortality and size of abdominal aortic aneurysm at long-term follow-up of patients not treated surgically and treated with and without statins. Am J Cardiol. 2006;97(2):279–80.  https://doi.org/10.1016/j.amjcard.2005.08.033.CrossRefPubMedGoogle Scholar
  89. 89.
    Desai H, Aronow WS, Ahn C, et al. Incidence of perioperative myocardial infarction and of 2-year mortality in 577 elderly patients undergoing noncardiac vascular surgery treated with and without statins. Arch Gerontol Geriatr. 2010;51(2):149–51.  https://doi.org/10.1016/j.archger.2009.09.042.CrossRefPubMedGoogle Scholar
  90. 90.
    Lai HM, Aronow WS, Mercando AD, et al. Risk factor reduction in progression of angiographic coronary artery disease. Arch Med Sci. 2012;8(3):444–8.  https://doi.org/10.5114/aoms.2012.29399.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Lai HM, Aronow WS, Kruger A, et al. Effect of beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins on mortality in patients with implantable cardioverter-defibrillators. Am J Cardiol. 2008;102(1):77–8.  https://doi.org/10.1016/j.amjcard.2008.02.103.CrossRefPubMedGoogle Scholar
  92. 92.
    Desai H, Aronow WS, Tsai FS, et al. Statins reduce appropriate cardioverter-defibrillator shocks and mortality in patients with heart failure and combined cardiac resynchronization and implantable cardioverter-defibrillator therapy. J Cardiovasc Pharmacol Ther. 2009;14(3):176–9.  https://doi.org/10.1177/1074248409340157.CrossRefPubMedGoogle Scholar
  93. 93.
    Desai H, Aronow WS, Ahn C, et al. Incidence of appropriate cardioverter-defibrillator shocks and mortality in patients with heart failure treated with combined cardiac resynchronization plus implantable cardioverter-defibrillator therapy versus implantable cardioverter-defibrillator therapy. J Cardiovasc Pharmacol Ther. 2010;15(1):37–40.  https://doi.org/10.1177/1074248409351408.CrossRefPubMedGoogle Scholar
  94. 94.
    Desai H, Aronow WS, Ahn C, et al. Risk factors for appropriate cardioverter-defibrillator shocks, inappropriate cardioverter-defibrillator shocks, and time to mortality in 549 patients with heart failure. Am J Cardiol. 2010;105(9):1336–8.  https://doi.org/10.1016/j.amjcard.2009.12.057.CrossRefPubMedGoogle Scholar
  95. 95.
    Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333(20):1301–7.  https://doi.org/10.1056/NEJM199511163332001.CrossRefPubMedGoogle Scholar
  96. 96.
    Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279(20):1615–22.CrossRefPubMedGoogle Scholar
  97. 97.
    Sever PS, Dahlöf 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(9364):1149–58.  https://doi.org/10.1016/S0140-6736(03)12948-0.CrossRefPubMedGoogle Scholar
  98. 98.
    Neil HAW, 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;29(11):2378–84.  https://doi.org/10.2337/dc06-0872.CrossRefPubMedGoogle Scholar
  99. 99.
    Nakaya N, Mizuno K, Ohashi Y, et al. Low-dose pravastatin and age-related differences in risk factors for cardiovascular disease in hypercholesterolaemic Japanese: analysis of the management of elevated cholesterol in the primary prevention group of adult Japanese (MEGA study). Drugs Aging. 2011;28(9):681–92.  https://doi.org/10.2165/11595620-000000000-00000.CrossRefPubMedGoogle Scholar
  100. 100.
    Glynn RJ, Koenig W, Nordestgaard BG, Shepherd J, Ridker PM. Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average low-density lipoprotein cholesterol levels: exploratory analysis of a randomized trial. Ann Intern Med. 2010;152(8):488–496, W174.  https://doi.org/10.7326/0003-4819-152-8-201004200-00005.CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Savarese G, Gotto AM, Paolillo S, et al. Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis. J Am Coll Cardiol. 2013;62(22):2090–9.  https://doi.org/10.1016/j.jacc.2013.07.069.CrossRefPubMedGoogle Scholar
  102. 102.
    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;32(8):649–61.  https://doi.org/10.1007/s40266-015-0290-9.CrossRefPubMedGoogle Scholar
  103. 103.
    Yusuf S, Bosch J, Dagenais G, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374(21):2021–31.  https://doi.org/10.1056/NEJMoa1600176.CrossRefPubMedGoogle Scholar
  104. 104.
    Han BH, Sutin D, Williamson JD, et al. Effect of statin treatment vs usual care on primary cardiovascular prevention among older adults: the ALLHAT-LLT randomized clinical trial. JAMA Intern Med. 2017;177(7):955–65.  https://doi.org/10.1001/jamainternmed.2017.1442.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Ramos R, Comas-Cufí M, Martí-Lluch R, et al. Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study. BMJ. 2018;362:k3359.  https://doi.org/10.1136/bmj.k3359.CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Wei MY, Ito MK, Cohen JD, Brinton EA, Jacobson TA. 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;7(5):472–83.  https://doi.org/10.1016/j.jacl.2013.03.001.CrossRefPubMedGoogle Scholar
  107. 107.
    Bruckert E, Hayem G, Dejager S, Yau C, Bégaud B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients–the PRIMO study. Cardiovasc Drugs Ther. 2005;19(6):403–14.  https://doi.org/10.1007/s10557-005-5686-z.CrossRefPubMedGoogle Scholar
  108. 108.
    Newman CB, Palmer G, Silbershatz H, Szarek M. Safety of atorvastatin derived from analysis of 44 completed trials in 9,416 patients. Am J Cardiol. 2003;92(6):670–6.CrossRefPubMedGoogle Scholar
  109. 109.
    Zhang H, Plutzky J, Skentzos S, et al. Discontinuation of statins in routine care settings: a cohort study. Ann Intern Med. 2013;158(7):526–34.  https://doi.org/10.7326/0003-4819-158-7-201304020-00004.CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Neal RC, Ferdinand KC, Ycas J, Miller E. Relationship of ethnic origin, gender, and age to blood creatine kinase levels. Am J Med. 2009;122(1):73–8.  https://doi.org/10.1016/j.amjmed.2008.08.033.CrossRefPubMedGoogle Scholar
  111. 111.
    Mampuya WM, Frid D, Rocco M, et al. Treatment strategies in patients with statin intolerance: the Cleveland Clinic experience. Am Heart J. 2013;166(3):597–603.  https://doi.org/10.1016/j.ahj.2013.06.004.CrossRefPubMedPubMedCentralGoogle Scholar
  112. 112.
    Rosenson RS, Baker SK, Jacobson TA, Kopecky SL, Parker BA, The National Lipid Association’s Muscle Safety Expert Panel. An assessment by the Statin Muscle Safety Task Force: 2014 update. J Clin Lipidol. 2014;8(3 Suppl):S58–71.  https://doi.org/10.1016/j.jacl.2014.03.004.CrossRefPubMedGoogle Scholar
  113. 113.
    Pasternak RC, Smith SC, Bairey-Merz CN, et al. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. J Am Coll Cardiol. 2002;40(3):567–72.CrossRefPubMedGoogle Scholar
  114. 114.
    Tikkanen MJ, Holme I, Cater NB, et al. Comparison of efficacy and safety of atorvastatin (80 mg) to simvastatin (20 to 40 mg) in patients aged <65 versus >or=65 years with coronary heart disease (from the Incremental DEcrease through Aggressive Lipid Lowering [IDEAL] study). Am J Cardiol. 2009;103(5):577–82.  https://doi.org/10.1016/j.amjcard.2008.10.029.CrossRefPubMedGoogle Scholar
  115. 115.
    Research C for DE and Drug safety and availability. FDA Drug Safety Communication: important safety label changes to cholesterol-lowering statin drugs. https://www.fda.gov/Drugs/DrugSafety/ucm293101.htm. Accessed 13 Sep 2018.
  116. 116.
    Brown AF, Mangione CM, Saliba D, Sarkisian CA, California Healthcare Foundation/American Geriatrics Society Panel on Improving Care for Elders with Diabetes. Guidelines for improving the care of the older person with diabetes mellitus. J Am Geriatr Soc. 2003;51(5 Suppl Guidelines):S265–80.  https://doi.org/10.1046/j.1532-5415.51.5s.1.x.CrossRefPubMedGoogle Scholar
  117. 117.
    Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735–42.  https://doi.org/10.1016/S0140-6736(09)61965-6.CrossRefPubMedGoogle Scholar
  118. 118.
    Waters DD, Ho JE, DeMicco DA, et al. Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. J Am Coll Cardiol. 2011;57(14):1535–45.  https://doi.org/10.1016/j.jacc.2010.10.047.CrossRefPubMedGoogle Scholar
  119. 119.
    Preiss D, Seshasai SRK, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305(24):2556–64.  https://doi.org/10.1001/jama.2011.860.CrossRefPubMedGoogle Scholar
  120. 120.
    Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA. 2002;288(4):462–7.CrossRefPubMedGoogle Scholar
  121. 121.
    Benner JS, Glynn RJ, Mogun H, Neumann PJ, Weinstein MC, Avorn J. Long-term persistence in use of statin therapy in elderly patients. JAMA. 2002;288(4):455–61.CrossRefPubMedGoogle Scholar
  122. 122.
    Tibrewala A, Jivan A, Oetgen WJ, Stone NJ. A comparative analysis of current lipid treatment guidelines: nothing stands still. J Am Coll Cardiol. 2018;71(7):794–9.  https://doi.org/10.1016/j.jacc.2017.12.025.CrossRefPubMedGoogle Scholar
  123. 123.
    Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force recommendation statement. JAMA. 2016;316(19):1997–2007.  https://doi.org/10.1001/jama.2016.15450.CrossRefPubMedGoogle Scholar
  124. 124.
    Goyal A, Gupta T, Aronow WS, Panza JA, Cooper HA. Making the case for universal treatment of hypercholesterolemia. Am J Cardiol. 2016;118(2):303–4.  https://doi.org/10.1016/j.amjcard.2016.04.027.CrossRefPubMedGoogle Scholar
  125. 125.
    Mortensen MB, Falk E. Primary prevention with statins in the elderly. J Am Coll Cardiol. 2018;71(1):85–94.  https://doi.org/10.1016/j.jacc.2017.10.080.CrossRefPubMedGoogle Scholar
  126. 126.
    Santosa S, Varady KA, AbuMweis S, Jones PJH. Physiological and therapeutic factors affecting cholesterol metabolism: does a reciprocal relationship between cholesterol absorption and synthesis really exist? Life Sci. 2007;80(6):505–14.  https://doi.org/10.1016/j.lfs.2006.10.006.CrossRefPubMedGoogle Scholar
  127. 127.
    Phan BAP, Dayspring TD, Toth PP. Ezetimibe therapy: mechanism of action and clinical update. Vasc Health Risk Manag. 2012;8:415–27 10.2147/VHRM.S33664.PubMedPubMedCentralGoogle Scholar
  128. 128.
    Pandor A, Ara RM, Tumur I, et al. Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. J Intern Med. 2009;265(5):568–80.  https://doi.org/10.1111/j.1365-2796.2008.02062.x.CrossRefPubMedGoogle Scholar
  129. 129.
    Morrone D, Weintraub WS, Toth PP, et al. Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: a pooled analysis of over 21,000 subjects from 27 clinical trials. Atherosclerosis. 2012;223(2):251–61.  https://doi.org/10.1016/j.atherosclerosis.2012.02.016.CrossRefPubMedGoogle Scholar
  130. 130.
    Zieve F, Wenger NK, Ben-Yehuda O, et al. Safety and efficacy of ezetimibe added to atorvastatin versus up titration of atorvastatin to 40 mg in patients > or = 65 years of age (from the ZETia in the ELDerly [ZETELD] study). Am J Cardiol. 2010;105(5):656–63.  https://doi.org/10.1016/j.amjcard.2009.10.029.CrossRefPubMedGoogle Scholar
  131. 131.
    Constance C, Ben-Yehuda O, Wenger NK, et al. Atorvastatin 10 mg plus ezetimibe versus titration to atorvastatin 40 mg: attainment of European and Canadian guideline lipid targets in high-risk subjects ≥65 years. Lipids Health Dis. 2014;13:13.  https://doi.org/10.1186/1476-511X-13-13.CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Lipka L, Sager P, Strony J, et al. Efficacy and safety of coadministration of ezetimibe and statins in elderly patients with primary hypercholesterolaemia. Drugs Aging. 2004;21(15):1025–32.CrossRefPubMedGoogle Scholar
  133. 133.
    Foody JM, Brown WV, Zieve F, et al. Safety and efficacy of ezetimibe/simvastatin combination versus atorvastatin alone in adults ≥65 years of age with hypercholesterolemia and with or at moderately high/high risk for coronary heart disease (the VYTELD study). Am J Cardiol. 2010;106(9):1255–63.  https://doi.org/10.1016/j.amjcard.2010.06.051.CrossRefPubMedGoogle Scholar
  134. 134.
    Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–97.  https://doi.org/10.1056/NEJMoa1410489.CrossRefPubMedGoogle Scholar
  135. 135.
    Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2017 focused update of the 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2017;70(14):1785–822.  https://doi.org/10.1016/j.jacc.2017.07.745.CrossRefPubMedGoogle Scholar
  136. 136.
    Zeman M, Vecka M, Perlík, et al. Niacin in the treatment of hyperlipidemias in light of new clinical trials: has niacin lost its place? Med Sci Monit. 2015;21:2156–62.  https://doi.org/10.12659/MSM.893619.CrossRefPubMedPubMedCentralGoogle Scholar
  137. 137.
    Bodor ET, Offermanns S. Nicotinic acid: an old drug with a promising future. Br J Pharmacol. 2008;153(Suppl 1):S68–75.  https://doi.org/10.1038/sj.bjp.0707528.CrossRefPubMedGoogle Scholar
  138. 138.
    Carlson LA, Danielson M, Ekberg I, Klintemar B, Rosenhamer G. Reduction of myocardial reinfarction by the combined treatment with clofibrate and nicotinic acid. Atherosclerosis. 1977;28(1):81–6.CrossRefPubMedGoogle Scholar
  139. 139.
    Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in Blacks with heart failure. N Engl J Med. 2004;351(20):2049–57.  https://doi.org/10.1056/NEJMoa042934.CrossRefPubMedGoogle Scholar
  140. 140.
    Taylor AJ, Villines TC, Stanek EJ, et al. Extended-release niacin or ezetimibe and carotid intima–media thickness. N Engl J Med. 2009;361(22):2113–22.  https://doi.org/10.1056/NEJMoa0907569.CrossRefPubMedGoogle Scholar
  141. 141.
    AIM-HIGH Investigators, Boden WE, Probstfield JL, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–67.  https://doi.org/10.1056/NEJMoa1107579.CrossRefGoogle Scholar
  142. 142.
    HPS2-THRIVE Collaborative Group, Landray MJ, Haynes R, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–12.  https://doi.org/10.1056/NEJMoa1300955.CrossRefGoogle Scholar
  143. 143.
    Lloyd-Jones DM. Niacin and HDL cholesterol–time to face facts. N Engl J Med. 2014;371(3):271–3.  https://doi.org/10.1056/NEJMe1406410.CrossRefPubMedGoogle Scholar
  144. 144.
    Marais DA, Blom DJ, Petrides F, Gouëffic Y, Lambert G. Proprotein convertase subtilisin/kexin type 9 inhibition. Curr Opin Lipidol. 2012;23(6):511–7.  https://doi.org/10.1097/MOL.0b013e3283587563.CrossRefPubMedGoogle Scholar
  145. 145.
    Dullaart RPF. PCSK9 inhibition to reduce cardiovascular events. N Engl J Med. 2017;376(18):1790–1.  https://doi.org/10.1056/NEJMe1703138.CrossRefPubMedGoogle Scholar
  146. 146.
    Ridker PM, Revkin J, Amarenco P, et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med. 2017;376(16):1527–39.  https://doi.org/10.1056/NEJMoa1701488.CrossRefPubMedGoogle Scholar
  147. 147.
    Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1500–9.  https://doi.org/10.1056/NEJMoa1500858.CrossRefPubMedGoogle Scholar
  148. 148.
    Koren M, Rosenson R, Khan B, et al. LDL cholesterol reduction in elderly patients with the PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of 1779 patients in phase 2, 3 and open label extension studies [abstract]. J Am Coll Cardiol. 2018;65(10 Suppl):A1366.  https://doi.org/10.1016/S0735-1097(15)61366-3.CrossRefGoogle Scholar
  149. 149.
    Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–22.  https://doi.org/10.1056/NEJMoa1615664.CrossRefPubMedGoogle Scholar
  150. 150.
    Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration, Sarwar N, Sandhu MS, et al. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet. 2010;375(9726):1634–9.  https://doi.org/10.1016/S0140-6736(10)60545-4.CrossRefPubMedCentralGoogle Scholar
  151. 151.
    Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298(3):299–308.  https://doi.org/10.1001/jama.298.3.299.CrossRefPubMedGoogle Scholar
  152. 152.
    Miller M. Dyslipidemia and cardiovascular risk: the importance of early prevention. QJM. 2009;102(9):657–67.  https://doi.org/10.1093/qjmed/hcp065.CrossRefPubMedPubMedCentralGoogle Scholar
  153. 153.
    Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987;317(20):1237–45.  https://doi.org/10.1056/NEJM198711123172001.CrossRefPubMedGoogle Scholar
  154. 154.
    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(6):410–8.  https://doi.org/10.1056/NEJM199908053410604.CrossRefPubMedGoogle Scholar
  155. 155.
    Keech A, Simes RJ, Barter P, et al. 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;366(9500):1849–61.  https://doi.org/10.1016/S0140-6736(05)67667-2.CrossRefPubMedGoogle Scholar
  156. 156.
    ACCORD Study Group, Ginsberg HN, Elam MB, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–74.  https://doi.org/10.1056/NEJMoa1001282.CrossRefGoogle Scholar
  157. 157.
    Jun M, Foote C, Lv J, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010;375(9729):1875–84.  https://doi.org/10.1016/S0140-6736(10)60656-3.CrossRefPubMedGoogle Scholar
  158. 158.
    Bruckert E, Labreuche J, Deplanque D, Touboul P-J, Amarenco P. Fibrates effect on cardiovascular risk is greater in patients with high triglyceride levels or atherogenic dyslipidemia profile: a systematic review and meta-analysis. J Cardiovasc Pharmacol. 2011;57(2):267–72.  https://doi.org/10.1097/FJC.0b013e318202709f.CrossRefPubMedGoogle Scholar
  159. 159.
    Lee M, Saver JL, Towfighi A, Chow J, Ovbiagele B. Efficacy of fibrates for cardiovascular risk reduction in persons with atherogenic dyslipidemia: a meta-analysis. Atherosclerosis. 2011;217(2):492–8.  https://doi.org/10.1016/j.atherosclerosis.2011.04.020.CrossRefPubMedGoogle Scholar
  160. 160.
    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.  https://doi.org/10.1136/bmj.h2335.CrossRefPubMedPubMedCentralGoogle Scholar
  161. 161.
    Zhao YY, Weir MA, Manno M, et al. New fibrate use and acute renal outcomes in elderly adults: a population-based study. Ann Intern Med. 2012;156(8):560–9.  https://doi.org/10.7326/0003-4819-156-8-201204170-00003.CrossRefPubMedGoogle Scholar
  162. 162.
    Lee JH, O’Keefe JH, Lavie CJ, Harris WS. Omega-3 fatty acids: cardiovascular benefits, sources and sustainability. Nat Rev Cardiol. 2009;6(12):753–8.  https://doi.org/10.1038/nrcardio.2009.188.CrossRefPubMedGoogle Scholar
  163. 163.
    Bowen KJ, Harris WS, Kris-Etherton PM. Omega-3 fatty acids and cardiovascular disease: are there benefits? Curr Treat Options Cardiovasc Med. 2016;18(11):69.  https://doi.org/10.1007/s11936-016-0487-1.CrossRefPubMedPubMedCentralGoogle Scholar
  164. 164.
    Abdelhamid AS, Brown TJ, Brainard JS, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2018;7:CD003177.  https://doi.org/10.1002/14651858.CD003177.pub3.CrossRefPubMedGoogle Scholar
  165. 165.
    Kromhout D, Giltay EJ, Geleijnse JM, Alpha Omega Trial Group. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med. 2010;363(21):2015–26.  https://doi.org/10.1056/NEJMoa1003603.CrossRefPubMedGoogle Scholar
  166. 166.
    Rauch B, Schiele R, Schneider S, et al. OMEGA, a randomized, placebo-controlled trial to test the effect of highly purified omega-3 fatty acids on top of modern guideline-adjusted therapy after myocardial infarction. Circulation. 2010;122(21):2152–9.  https://doi.org/10.1161/CIRCULATIONAHA.110.948562.CrossRefPubMedGoogle Scholar
  167. 167.
    Galan P, Kesse-Guyot E, Czernichow S, Briancon S, Blacher J, Hercberg S. Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ. 2010;341:c6273.  https://doi.org/10.1136/bmj.c6273.CrossRefPubMedPubMedCentralGoogle Scholar
  168. 168.
    ORIGIN Trial Investigators, Bosch J, Gerstein HC, et al. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012;367(4):309–18.  https://doi.org/10.1056/NEJMoa1203859.CrossRefGoogle Scholar
  169. 169.
    Risk and Prevention Study Collaborative Group, Roncaglioni MC, Tombesi M, et al. n-3 fatty acids in patients with multiple cardiovascular risk factors. N Engl J Med. 2013;368(19):1800–8.  https://doi.org/10.1056/NEJMoa1205409.CrossRefGoogle Scholar
  170. 170.
    Aung T, Halsey J, Kromhout D, Omega-3 Treatment Trialists’ Collaboration, et al. Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77 917 individuals. JAMA Cardiol. 2018;3(3):225–34.  https://doi.org/10.1001/jamacardio.2017.5205.CrossRefPubMedPubMedCentralGoogle Scholar
  171. 171.
    Bhatt DL, Steg PG, Miller M, REDUCE-IT Investigators, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2018.  https://doi.org/10.1056/NEJMoa1812792.CrossRefPubMedPubMedCentralGoogle Scholar
  172. 172.
    Blair HA, Dhillon S. Omega-3 carboxylic acids (Epanova): a review of its use in patients with severe hypertriglyceridemia. Am J Cardiovasc Drugs. 2014;14(5):393–400.  https://doi.org/10.1007/s40256-014-0090-3.CrossRefPubMedGoogle Scholar
  173. 173.
    AstraZeneca. Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia (STRENGTH). US National Institutes of Health. https://clinicaltrials.gov/ct2/show/NCT02104817. Accessed 30 Nov 2018

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Srikanth Yandrapalli
    • 1
  • Shashvat Gupta
    • 2
  • Gabriela Andries
    • 2
  • Howard A. Cooper
    • 1
  • Wilbert S. Aronow
    • 1
  1. 1.Cardiology DivisionWestchester Medical Center and New York Medical CollegeValhallaUSA
  2. 2.Department of MedicineWestchester Medical Center and New York Medical CollegeValhallaUSA

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