Skip to main content

Advertisement

Log in

Initiation of Statin Therapy: Are There Age Limits?

  • Statin Drugs (M Clearfield, Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Cardiovascular disease (CVD) is the leading cause of death, with a higher prevalence in older adults who form an increasing proportion of the population of the United States. Statin treatment reduces cardiovascular morbidity and mortality in middle-aged adults. However, few studies have included older individuals, particularly ages 80 years or older. We review recent publications regarding primary and secondary prevention of CVD with statin therapy in older adults. Risk scores and their limitations in this population are discussed. The association of adverse effects with intensive doses of statin and their interactions with other drugs may be more problematic in older adults. Statin therapy appears cost-effective for individuals with higher CVD risk but this is dependent on the assumptions used. Evidence remains limited regarding the overall benefit of starting statin therapy in adults ages 80 years and older; thus, clinical judgment remains necessary in making this decision.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Wald NJ, Simmonds M, Morris JK: Screening for future cardiovascular disease using age alone compared with multiple risk factors and age. PLoS One, 6:e18742.

  2. Committee on the Future Health Care Workforce for Older Americans. Institute of Medicine. Retooling for an Aging America: Building the Health Care Workforce. 2008 August 4, 2008.

  3. Forman DE, Rich MW, Alexander KP, et al. Cardiac care for older adults. Time for a new paradigm. J Am Coll Cardiol. 2011;57:1801–10.

    Article  PubMed  Google Scholar 

  4. 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;106:3143–421.

    Google Scholar 

  5. Holmes MV, Harrison S, Talmud PJ, et al. Utility of genetic determinants of lipids and cardiovascular events in assessing risk. Nat Rev Cardiol. 2011;8:207–21.

    Article  PubMed  CAS  Google Scholar 

  6. LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA. 1999;282:2340–6.

    Article  PubMed  CAS  Google Scholar 

  7. Long SB, Blaha MJ, Blumenthal RS, Michos ED. Clinical utility of rosuvastatin and other statins for cardiovascular risk reduction among the elderly. Clin Interv Aging. 2010;6:27–35.

    PubMed  Google Scholar 

  8. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623–30.

    Article  PubMed  CAS  Google Scholar 

  9. 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;115:700–7.

    Article  PubMed  CAS  Google Scholar 

  10. Gransbo K, Melander O, Wallentin L, et al. Cardiovascular and cancer mortality in very elderly post-myocardial infarction patients receiving statin treatment. J Am Coll Cardiol. 2010;55:1362–9.

    Article  PubMed  Google Scholar 

  11. Rahilly-Tierney CR, Lawler EV, Scranton RE, Gaziano JM. Cardiovascular benefit of magnitude of low-density lipoprotein cholesterol reduction: a comparison of subgroups by age. Circulation. 2009;120:1491–7.

    Article  PubMed  CAS  Google Scholar 

  12. Lemaitre RN, Psaty BM, Heckbert SR, et al. Therapy with hydroxymethylglutaryl coenzyme a reductase inhibitors (statins) and associated risk of incident cardiovascular events in older adults: evidence from the Cardiovascular Health Study. Arch Intern Med. 2002;162:1395–400.

    Article  PubMed  CAS  Google Scholar 

  13. 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;279:1615–22.

    Article  PubMed  CAS  Google Scholar 

  14. 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 tria. Lancet. 2003;361:1149–58.

    Article  PubMed  CAS  Google Scholar 

  15. Nakamura H, Arakawa K, Itakura H, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet. 2006;368:1155–63.

    Article  PubMed  CAS  Google Scholar 

  16. 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;364:685–96.

    Article  PubMed  CAS  Google Scholar 

  17. 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;29:2378–84.

    Article  PubMed  CAS  Google Scholar 

  18. Knopp RH, d’Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus (ASPEN). Diabetes Care. 2006;29:1478–85.

    Article  PubMed  CAS  Google Scholar 

  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;359:2195–207.

    Article  PubMed  CAS  Google Scholar 

  20. Koenig W, Ridker PM. Rosuvastatin for primary prevention in patients with European systematic coronary risk evaluation risk >/= 5% or Framingham risk >20%: post hoc analyses of the JUPITER trial requested by European health authorities. Eur Heart J. 2011;32:75–83.

    Article  PubMed  CAS  Google Scholar 

  21. • Glynn RJ, Koenig W, Nordestgaard BG, et al.: 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, 152:488–96, W174. This is a retrospective analysis of older patients (aged ≥70 years) in JUPITER to assess whether 20 mg of rosuvastatin is safe and efficacious in reducing cardiovascular events. The older patients had a significant reduction in cardiovascular events without an increase in adverse events.

    PubMed  Google Scholar 

  22. Ridker PM, Macfadyen JG, Nordestgaard BG, et al. Rosuvastatin for primary prevention among individuals with elevated high-sensitivity c-reactive protein and 5–10% and 10–20% 10-year risk. Implications of the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial for “intermediate risk”. Circ Cardiovasc Qual Outcomes. 2010;3:447–52.

    Article  PubMed  Google Scholar 

  23. Ray KK, Seshasai SR, Erqou S, et al. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med. 2010;170:1024–31.

    Article  PubMed  CAS  Google Scholar 

  24. Brugts JJ, Yetgin T, Hoeks SE, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ. 2009;338:b2376–431.

    Article  PubMed  CAS  Google Scholar 

  25. 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;376:1670–81.

    Article  PubMed  CAS  Google Scholar 

  26. Rosengren A, Wallentin L, Simoons M, et al. Age, clinical presentation, and outcome of acute coronary syndromes in the Euroheart acute coronary syndrome survey. Eur Heart J. 2006;27:789–95.

    Article  PubMed  Google Scholar 

  27. Ko DT, Mamdani M, Alter DA. Lipid-lowering therapy with statins in high-risk elderly patients: the treatment-risk paradox. JAMA. 2004;291:1864–70.

    Article  PubMed  CAS  Google Scholar 

  28. Simons LA, Ortiz M, Calcino G. Long term persistence with statin therapy - experience in Australia 2006–2010. Aust Fam Physician. 2011;40:319–22.

    PubMed  Google Scholar 

  29. Itakura H, Nakaya N, Kusunoki T, et al. Long-term event monitoring study of fluvastatin in Japanese patients with hypercholesterolemia: Efficacy and incidence of cardiac and other events in elderly patients (>/= 65 years old). J Cardiol. 2010;57:77–88.

    PubMed  Google Scholar 

  30. Holbrook A, Wright M, Sung M, et al. Statin-associated rhabdomyolysis: is there a dose–response relationship? Can J Cardiol. 2011;27:146–51.

    Article  PubMed  Google Scholar 

  31. Armitage J, Bowman L, Wallendszus K, et al. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet. 2010;376:1658–69.

    Article  PubMed  Google Scholar 

  32. Egan A, Colman E: Weighing the benefits of high-dose simvastatin against the risk of myopathy. N Engl J Med, 365:285–7.

  33. Alexander KP, Blazing MA, Rosenson RS, et al. Management of hyperlipidemia in older adults. J Cardiovasc Pharmacol Ther. 2009;14:49–58.

    Article  PubMed  CAS  Google Scholar 

  34. • Hippisley-Cox J, Coupland C: Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ 2010, 340:c2197. This is a large, prospective cohort study evaluating the benefits and harms of statin therapy that included patients up to age 84 years. Potential outcomes, including effects on cardiac, neurologic, musculoskeletal, renal, hepatic, hematologic, oncologic, ophthalmologic, and rheumatologic organ systems, were evaluated. Statins were associated with a decline in esophageal cancer but increased liver dysfunction, acute renal failure, myopathy, and cataracts.

    Article  PubMed  Google Scholar 

  35. Sandhu S, Wiebe N, Fried LF, Tonelli M. Statins for improving renal outcomes: a meta-analysis. J Am Soc Nephrol. 2006;17:2006–16.

    Article  PubMed  CAS  Google Scholar 

  36. Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305:2556–64.

    Article  PubMed  CAS  Google Scholar 

  37. Mills EJ, Wu P, Chong G, et al. Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. QJM. 2011;104:109–24.

    Article  PubMed  CAS  Google Scholar 

  38. • Sattar N, Preiss D, Murray HM, et al.: Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet 2010, 375:735–42. This is a meta-analysis of 13 trials of 91,140 patients evaluating the risk of diabetes with statin therapy. The absolute risk of diabetes due to statin therapy remained low. The study is notable due to the large sample size and the mix of both primary and secondary prevention patients.

    Article  PubMed  CAS  Google Scholar 

  39. 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.

    PubMed  Google Scholar 

  40. Clarke AT, Mills PR. Atorvastatin associated liver disease. Dig Liver Dis. 2006;38:772–7.

    Article  PubMed  CAS  Google Scholar 

  41. Padala KP, Padala PR, Potter JF. Statins: a case for drug withdrawal in patients with dementia. J Am Geriatr Soc. 2010;58:1214–6.

    Article  PubMed  Google Scholar 

  42. Garfinkel D, Mangin D. Feasibility study of a systematic approach for discontinuation of multiple medications in older adults: addressing polypharmacy. Arch Intern Med. 2010;170:1648–54.

    Article  PubMed  Google Scholar 

  43. Jyrkka J, Vartiainen L, Hartikainen S, et al. Increasing use of medicines in elderly persons: a five-year follow-up of the Kuopio 75 + Study. Eur J Clin Pharmacol. 2006;62:151–8.

    Article  PubMed  Google Scholar 

  44. Goldberg RM, Mabee J, Chan L, Wong S. Drug-drug and drug-disease interactions in the ED: analysis of a high-risk population. Am J Emerg Med. 1996;14:447–50.

    Article  PubMed  CAS  Google Scholar 

  45. • Fleg JL, Aronow WS, Frishman WH: Cardiovascular drug therapy in the elderly: benefits and challenges. Nat Rev Cardiol 2011, 8:13–28. This is an excellent overview on the treatment of cardiovascular diseases in the elderly, focusing on evidence-based therapies, physiologic alterations in the elderly affecting medication metabolism and efficacy, and polypharmacy issues.

    Article  PubMed  CAS  Google Scholar 

  46. Roten L, Schoenenberger RA, Krahenbuhl S, Schlienger RG. Rhabdomyolysis in association with simvastatin and amiodarone. Ann Pharmacother. 2004;38:978–81.

    Article  PubMed  Google Scholar 

  47. Enger C, Gately R, Ming EE, et al. Pharmacoepidemiology safety study of fibrate and statin concomitant therapy. Am J Cardiol. 2010;106:1594–601.

    Article  PubMed  CAS  Google Scholar 

  48. Sirtori CR, Mombelli G, Triolo M, Laaksonen R: Clinical response to statins: Mechanism(s) of variable activity and adverse effects. Ann Med 2011.

  49. Wilson PW, D’Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:1837–47.

    PubMed  CAS  Google Scholar 

  50. D’Agostino Sr RB, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117:743–53.

    Article  PubMed  Google Scholar 

  51. Ridker PM, Buring JE, Rifai N, Cook NR. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. JAMA. 2007;297:611–9.

    Article  PubMed  CAS  Google Scholar 

  52. Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005;352:1293–304.

    Article  PubMed  CAS  Google Scholar 

  53. Ridker PM, Paynter NP, Rifai N, et al. C-reactive protein and parental history improve global cardiovascular risk prediction: the Reynolds Risk Score for men. Circulation. 2008;118:2243–51.

    Article  PubMed  CAS  Google Scholar 

  54. Foody JM, Krumholz HM. Are statins indicated for the primary prevention of CAD in octogenarians? antagonist viewpoint. Am J Geriatr Cardiol. 2003;12:357–60.

    Article  PubMed  Google Scholar 

  55. Krumholz HM, Seeman TE, Merrill SS, et al. Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years. JAMA. 1994;272:1335–40.

    Article  PubMed  CAS  Google Scholar 

  56. 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;370:1829–39.

    Article  PubMed  Google Scholar 

  57. Hippisley-Cox J, Coupland C, Vinogradova Y, et al. Derivation and validation of QRISK, a new cardiovascular disease risk score for the United Kingdom: prospective open cohort study. BMJ. 2007;335:136.

    Article  PubMed  Google Scholar 

  58. Hippisley-Cox J, Coupland C, Robson J, Brindle P. Derivation, validation, and evaluation of a new QRISK model to estimate lifetime risk of cardiovascular disease: cohort study using QResearch database. BMJ. 2010;341:c6624.

    Article  PubMed  Google Scholar 

  59. Haq IU, Jackson PR, Yeo WW, Ramsay LE. Sheffield risk and treatment table for cholesterol lowering for primary prevention of coronary heart disease. Lancet. 1995;346:1467–71.

    Article  PubMed  CAS  Google Scholar 

  60. • Weatherley ND, Jackson PR: The new Sheffield risk and benefit tables for the elderly. QJM 2011, 104:3–12. The new Sheffield table evaluates the risk and benefit of blood pressure control and statin therapy in individuals older than 75 years. This article provides gender-specific tables to predict the potential gain from taking antihypertensive medication or a statin for a combination of age and risk factor score.

    Article  PubMed  CAS  Google Scholar 

  61. Simons LA, Simons J, Friedlander Y, et al. Risk functions for prediction of cardiovascular disease in elderly Australians: the Dubbo Study. Med J Aust. 2003;178:113–6.

    PubMed  Google Scholar 

  62. Polonsky TS, McClelland RL, Jorgensen NW, et al. Coronary artery calcium score and risk classification for coronary heart disease prediction. JAMA. 2010;303:1610–6.

    Article  PubMed  CAS  Google Scholar 

  63. Paramsothy P, Katz R, Owens DS, et al. Age-modification of lipoprotein, lipid, and lipoprotein ratio-associated risk for coronary artery calcium (from the Multi-Ethnic Study of Atherosclerosis [MESA]). Am J Cardiol. 2010;105:352–8.

    Article  PubMed  CAS  Google Scholar 

  64. Choudhry NK, Patrick AR, Glynn RJ, Avorn J. The cost-effectiveness of C-reactive protein testing and rosuvastatin treatment for patients with normal cholesterol levels. J Am Coll Cardiol. 2011;57:784–91.

    Article  PubMed  Google Scholar 

  65. • Greving JP, Visseren FL, de Wit GA, Algra A: Statin treatment for primary prevention of vascular disease: whom to treat? Cost-effectiveness analysis. BMJ 2011, 342:d1672. This is a cost-effectiveness analysis of low-dose statins in men and women aged 45 to 75 years without vascular disease at different degrees of risk for vascular disease using real-world cost and nonadherence estimates. The treatment effect of statins on reducing CVD was obtained from a recent meta-analysis of 10 randomized, controlled primary prevention statin trials. This trial demonstrated that a low-dose statin at low vascular disease was not cost-effective, but as the vascular risk increased so did the cost-effectiveness of low-dose statin.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

No conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pamela Ouyang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Desai, D.A., Zakaria, S. & Ouyang, P. Initiation of Statin Therapy: Are There Age Limits?. Curr Atheroscler Rep 14, 17–25 (2012). https://doi.org/10.1007/s11883-011-0220-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11883-011-0220-1

Keywords

Navigation