Skip to main content
SpringerLink
Log in

Statins for Primary Prevention of Cardiovascular Disease in Elderly Patients: Systematic Review and Meta-Analysis

  • Systematic Review
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Background

Statins have been shown to be beneficial in primary and secondary prevention settings; however, their role in the elderly remains a clinical conundrum, given that age-related factors could alter the risk–benefit ratio of statin treatment. This study aimed to critically evaluate the efficacy and safety of statins for primary prevention of cardiovascular disease (CVD) in the elderly.

Methods

We systematically reviewed randomized controlled trials comparing any statins with placebo or usual care for primary prevention of CVD in subjects aged ≥65 years. Relative risks (RRs) using a random effects model were calculated and sensitivity analyses were performed to assess the robustness of findings.

Results

Eight studies (n = 25,952) were included in the meta-analysis. Statins significantly reduced the risks of composite major adverse cardiovascular events (RR 0.82, 95 % CI 0.74–0.92), nonfatal myocardial infarction [MI] (0.75, 0.59–0.94) and total MI (0.74, 0.61–0.90). Treatment effects of statins were statistically insignificant in fatal MI (0.43, 0.09–2.01), stroke (fatal: 0.76, 0.24–2.45; nonfatal: 0.76, 0.53–1.11; total: 0.85, 0.68–1.06) and all-cause mortality (0.96, 0.88–1.04). Significant differences were not observed in myalgia (0.88, 0.69–1.13), elevation of hepatic transaminases (0.98, 0.71–1.34), new–onset diabetes (1.07, 0.77–1.48), serious adverse events (1.00, 0.97–1.04) and discontinuation due to adverse events (1.10, 0.85–1.42). The occurrence of myopathy, rhabdomyolysis and cognitive impairment was largely unreported in the included trials.

Conclusions

From a risk–benefit perspective, there is a role of statins for the primary prevention of major adverse cardiovascular events in elderly patients. Further studies are needed to ascertain the benefits of statins on fatal MI, stroke and all-cause mortality.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. World Health Organization. Global status report on noncommunicable diseases. 2014. http://www.who.int. Accessed 1 June 2015.

  2. Ducharme N, Radhamma R. Hyperlipidemia in the elderly. Clin Geriatr Med. 2008;24(3):471–87 (vi).

    Article  PubMed  Google Scholar 

  3. Chaplin S. Health survey for England 2013: the use of prescribed medicines. Prescriber. 2015;26(4):16–9.

    Article  Google Scholar 

  4. Gu QP, Paulose-Ram R, Burt VL, Kit BK. Prescription cholesterol-lowering medication use in adults aged 40 and over: United States, 2003–2012. NCHS data brief, no 177. Hyattsville: National Center for Health Statistics; 2014. http://www.cdc.gov/nchs/data/databriefs/db177.pdf. Accessed 1 June 2015.

  5. Naci H, Brugts JJ, Fleurence R, Tsoi B, Toor H, Ades AE. Comparative benefits of statins in the primary and secondary prevention of major coronary events and all-cause mortality: a network meta-analysis of placebo-controlled and active-comparator trials. Eur J Prev Cardiol. 2013;20(4):641–57.

    Article  PubMed  Google Scholar 

  6. Aronow WS. Statins reduce cardiovascular events in primary and secondary prevention trials without causing an increase in carcinoma. J Am Geriatr Soc. 2009;57(10):1942–3 (author reply 3–4).

    Article  PubMed  Google Scholar 

  7. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, 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.

    Article  CAS  PubMed  Google Scholar 

  8. Brugts JJ, Yetgin T, Hoeks SE, Gotto AM, Shepherd J, Westendorp RG, 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;1:CD004816.

    PubMed  Google Scholar 

  10. Minder CM, Blumenthal RS, Blaha MJ. Statins for primary prevention of cardiovascular disease: the benefits outweigh the risks. Curr Opin Cardiol. 2013;28(5):554–60.

    Article  PubMed  Google Scholar 

  11. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, 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.

    Article  PubMed  Google Scholar 

  12. Chokshi NP, Messerli FH, Sutin D, Supariwala AA, Shah NR. Appropriateness of statins in patients aged ≥80 years and comparison to other age groups. Am J Cardiol. 2012;110(10):1477–81.

    Article  CAS  PubMed  Google Scholar 

  13. Miedema MD, Lopez FL, Blaha MJ, Virani SS, Coresh J, Ballantyne CM, et al. Eligibility for statin therapy according to new cholesterol guidelines and prevalent use of medication to lower lipid levels in an older US Cohort: the Atherosclerosis Risk in Communities Study Cohort. JAMA Intern Med. 2015;175(1):138–40.

    Article  PubMed  Google Scholar 

  14. Petrone K, Katz P. Approaches to appropriate drug prescribing for the older adult. Prim Care. 2005;32(3):755–75.

    Article  PubMed  Google Scholar 

  15. Routledge PA, O’Mahony MS, Woodhouse KW. Adverse drug reactions in elderly patients. Br J Clin Pharmacol. 2004;57(2):121–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Cho S, Lau SW, Tandon V, Kumi K, Pfuma E, Abernethy DR. Geriatric drug evaluation: where are we now and where should we be in the future? Arch Intern Med. 2011;171(10):937–40.

    Article  PubMed  Google Scholar 

  17. Kronmal RA, Cain KC, Ye Z, Omenn GS. Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data. Arch Intern Med. 1993;153(9):1065–73.

    Article  CAS  PubMed  Google Scholar 

  18. Odden MC, Pletcher MJ, Coxson PG, Thekkethala D, Guzman D, Heller D, et al. Cost-effectiveness and population impact of statins for primary prevention in adults aged 75 years or older in the United States. Ann Intern Med. 2015;162(8):533–41.

    Article  PubMed  Google Scholar 

  19. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1–34.

    Article  PubMed  Google Scholar 

  20. Eder M, Feightner A, Webber E, Guirguis-Blake J, Whitlock E. Developing and selecting topic nominations for systematic reviews. Methods guide for comparative effectiveness reviews. Agency for Healthcare Research and Quality. November 2012. AHRQ publication no. 12(13)-EHC153-EF. http://www.effectivehealthcare.ahrq.gov/. Accessed 1 Aug 2014.

  21. Higgins JPT, Green S (eds). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. http://handbook.cochrane.org/. Accessed 1 Aug 2014.

  22. Ovbiagele B, Campbell S, Faiz A, Chambless LE. Relationship between non-specific prescription pill adherence and ischemic stroke outcomes. Cerebrovasc Dis. 2010;29(2):146–53.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Chen YH, Feng B, Chen ZW. Statins for primary prevention of cardiovascular and cerebrovascular events in diabetic patients without established cardiovascular diseases: a meta-analysis. Exp Clin Endocrinol Diabetes. 2012;120(2):116–20.

    Article  CAS  PubMed  Google Scholar 

  25. de Vries FM, Denig P, Pouwels KB, Postma MJ, Hak E. Primary prevention of major cardiovascular and cerebrovascular events with statins in diabetic patients: a meta-analysis. Drugs. 2012;72(18):2365–73.

    Article  PubMed  Google Scholar 

  26. Collaborators Cholesterol Treatment Trialists, Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, et al. 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.

    Article  Google Scholar 

  27. Ray KK, Seshasai SR, Erqou S, Sever P, Jukema JW, Ford I, 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(12):1024–31.

    Article  CAS  PubMed  Google Scholar 

  28. Tonelli M, Lloyd A, Clement F, Conly J, Husereau D, Hemmelgarn B, et al. Efficacy of statins for primary prevention in people at low cardiovascular risk: a meta-analysis. CMAJ. 2011;183(16):E1189–202.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Amarenco P, Labreuche J. Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol. 2009;8(5):453–63.

    Article  CAS  PubMed  Google Scholar 

  30. Mills EJ, Wu P, Chong G, Ghement I, Singh S, Akl EA, 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(2):109–24.

    Article  CAS  PubMed  Google Scholar 

  31. Naci H, Brugts JJ, Fleurence R, Ades AE. Comparative effects of statins on major cerebrovascular events: a multiple-treatments meta-analysis of placebo-controlled and active-comparator trials. QJM. 2013;106(4):299–306.

    Article  CAS  PubMed  Google Scholar 

  32. Ribeiro RA, Ziegelmann PK, Duncan BB, Stella SF, da Costa Vieira JL, Restelatto LM, et al. Impact of statin dose on major cardiovascular events: a mixed treatment comparison meta-analysis involving more than 175,000 patients. Int J Cardiol. 2013;166(2):431–9.

    Article  PubMed  Google Scholar 

  33. ALLHAT Officers and Coordinators for the ALLHAT Collaborative. Research Group, The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002;288(23):2998–3007.

    Article  Google Scholar 

  34. Collier DJ, Poulter NR, Dahlof B, Sever PS, Wedel H, Buch J, et al. Impact of atorvastatin among older and younger patients in the Anglo-Scandinavian Cardiac Outcomes Trial Lipid-Lowering Arm. J Hypertens. 2011;29(3):592–9.

    Article  CAS  PubMed  Google Scholar 

  35. Bruckert E, Lievre M, Giral P, Crepaldi G, Masana L, Vrolix M, et al. Short-term efficacy and safety of extended-release fluvastatin in a large cohort of elderly patients. Am J Geriatr Cardiol. 2003;12(4):225–31.

    Article  PubMed  Google Scholar 

  36. Neil HA, DeMicco DA, Luo D, Betteridge DJ, Colhoun HM, Durrington PN, 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.

    Article  CAS  PubMed  Google Scholar 

  37. Collins R, Armitage J, Parish S, Sleigh P, Peto R. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361(9374):2005–16.

    Article  PubMed  Google Scholar 

  38. 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):488–96 (W174).

    Article  PubMed Central  PubMed  Google Scholar 

  39. Nakaya N, Mizuno K, Ohashi Y, Teramoto T, Yokoyama S, Hirahara K, 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.

    Article  CAS  PubMed  Google Scholar 

  40. Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623–30.

    Article  CAS  PubMed  Google Scholar 

  41. Savarese G, Gotto AM Jr, Paolillo S, D’Amore C, Losco T, Musella F, et al. Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis. J Am Coll Cardiol. 2013;62(22):2090–9.

    Article  CAS  PubMed  Google Scholar 

  42. Amarenco P. Lipid lowering and recurrent stroke: another stroke paradox? Eur Heart J. 2005;26(18):1818–9.

    Article  PubMed  Google Scholar 

  43. Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol. 2006;97(8A):52C–60C.

    Article  CAS  PubMed  Google Scholar 

  44. Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305(24):2556–64.

    Article  CAS  PubMed  Google Scholar 

  45. Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation. 2004;109(23 Suppl 1):III50–7.

    PubMed  Google Scholar 

  46. Corsini A, Bellosta S, Baetta R, Fumagalli R, Paoletti R, Bernini F. New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacol Ther. 1999;84(3):413–28.

    Article  CAS  PubMed  Google Scholar 

  47. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735–42.

    Article  CAS  PubMed  Google Scholar 

  48. US FDA. FDA expands advice on statin risks. 2014. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm293330.htm. Accessed 1 June 2015.

  49. Ott BR, Daiello LA, Dahabreh IJ, Springate BA, Bixby K, Murali M, et al. Do statins impair cognition? A systematic review and meta-analysis of randomized controlled trials. J Gen Intern Med. 2015;30(3):348–58.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, 3 Fusionopolis Link, #03-08 Nexus@one-north, Singapore, 138543, Singapore

    Monica Teng, Liang Lin, Ying Jiao Zhao, Ai Leng Khoo & Boon Peng Lim

  2. University of Texas School of Public Health, Houston, TX, USA

    Barry R. Davis

  3. Department of Cardiology, Tan Tock Seng Hospital, Singapore, Singapore

    Quek Wei Yong

  4. Department of Cardiology, National University Heart Centre, Singapore, Singapore

    Tiong Cheng Yeo

Authors
  1. Monica Teng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liang Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Jiao Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ai Leng Khoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Barry R. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Quek Wei Yong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tiong Cheng Yeo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Boon Peng Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Monica Teng.

Ethics declarations

Funding

This study was not supported by any grants or organizations.

Conflicts of interest

Monica Teng, Liang Lin, Ying Jiao Zhao, Ai Leng Khoo, Barry R. Davis, Quek Wei Yong, Tiong Cheng Yeo and Boon Peng Lim declare that they have no conflicts of personal interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 20 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Teng, M., Lin, L., Zhao, Y.J. et al. Statins for Primary Prevention of Cardiovascular Disease in Elderly Patients: Systematic Review and Meta-Analysis. Drugs Aging 32, 649–661 (2015). https://doi.org/10.1007/s40266-015-0290-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-015-0290-9

Keywords

Search

Navigation