Tools for Practice


#344 Statins in Older Adults


CLINICAL QUESTION
In patients ≥65 years old, do the benefits of statins outweigh harms?


BOTTOM LINE
For primary prevention patients aged 65-75 years, statins likely result in a 16-39% relative reduction in major adverse cardiac events (MACE). For primary prevention patients aged >75, the benefit of initiating statins is unclear. However, there is no evidence to support stopping statins when primary prevention patients age over 75 (just because of age). For secondary prevention patients over 65 years (and over 75), statins result in ~20% relative reduction in MACE. Adverse events are similar to placebo.



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EVIDENCE
  • Seven systematic reviews1-7 of randomized controlled trials (RCTs) in a population age ≥65.
    •  Largest systematic review (26 RCTs, 186,854 patients, follow-up ~5 years) reported individualized patient data and analyzed by age (5-year categories) and by primary and secondary prevention.¹
    • Results statistically significant, unless stated.
  • Primary prevention:
    • Major adverse cardiac events (largest systematic review):¹
      • Patients >65 to <70 years: Relative risk (RR)=0.61 (0.51-0.73)
      • Patients >70 to <75 years: RR=0.84 (0.70-1.01)
      • Patients >75 years: RR=0.92 (0.73-1.16)
      • Another systematic review² found >65 (mean age 73): RR=0.82 (0.74-0.92)
      • Statins benefit on MACE appears to diminish in advanced age, with benefits likely extending to age 75. Beyond 75 years, uncertainty exists.
    • Mortality: No difference in all-cause mortality.2-4
  • Secondary prevention:
    • MACE: ~20% relative benefit across all ages,1 for example,
      • Patients 66-70 years: 4.3% versus 5.6% annually.¹
      • Patients age >75 years: 6.0% versus 6.8% annually.¹
    • Mortality: ~20% relative benefit in all-cause mortality.3,5
  • Adverse events:
    • No difference in overall,6 serious,2,6 or discontinuation due to adverse events.2,6
      • While an early RCT7 and systematic review8 raised concerns about increased cancer risk, subsequent studies do not support this risk.1,4,9
      • No RCTs/observational evidence of association between statins and dementia.10
CONTEXT
  • Guideline definitions and recommendations vary for older adults.11-15
  • MACE definitions vary between studies.
  • Upcoming key trials:
    • STAREE:16 ~10,000 primary prevention patients >70 years old determining effect of atorvastatin on death, disability, and MACE.
    • SITE:17 ~1200 primary prevention patients >75 years determining effect of stopping statins on all-cause mortality.


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Author(s):

  • Danielle Perry RN MSc
  • Michael R Kolber MD CCFP MSc

1. Cholesterol Treatment Trialists’ Collaboration. Lancet. 2019 Feb 2; 393(10170):407-15.

2. Teng M, Lin L, Zhao YJ, et al. Drugs Aging. 2015 Aug; 32(8):649-61.

3. Ponce OJ, Larrea-Mantilla L, Hemmingsen B, et al. J Clin Endocrinol Metab. 2019 May 1; 104(5):1585-94.

4. Savarese G, Gotto AM Jr, Paolillo S, D’Amore C, et al. J Am Coll Cardiol. 2013; 62(22):2090–2099.

5. Afilalo J, Duque G, Steele R, et al. J Am Coll Cardiol. 2008; 51(1): 37–45.

6. Zhou Z, Albarqouni L, Curtis AJ, et al. Drugs Aging. 2020 Mar; 37(3):175-85.

7. Shepherd J, Blauq GJ, Murphy MB, et al. Lancet. 2002 Nov 23; 360(9346):1623-30.

8. Roberts CG, Guallar E, Rodriguez A. J Gerontol A Biol Sci Med Sci. 2007 Aug; 62(8):879-87.

9. Lloyd SM, Stott DJ, de Craen AJM, et al. PLoS One. 2013 Sep 2; 8(9):e72642.

10. Moe SS, Young JP. Forget about it? Statins and the risk of dementia [Publication on the Internet] Tools for Practice #341. College of Family Physicians of Canada 2023 May 29. Available at: https://gomainpro.ca/wp-content/uploads/tools-for-practice/1683921732_tfp341_statinscognition.pdf Accessed 27-JUN-2023.

11. Grundy SM, Stone NJ, Bailey AL, et al. Circulation. 2019; 139:e1082-143.

12. O’Malley PG, Arnold MJ, Kelley C, et al. Ann Intern Med. 2020 Nov 17; 173(10):822-9.

13. Pearson GJ, Thanassoulis G, Anderson TJ, et al. Can J Cardiol. 2021 Aug; 37(8):1129-50.

14. Visseren FLJ, Mach F, Smulders YM, et al. Eur J Prev Cardiol. 2022 Feb 19; 29(1):5-115.

15. US Preventive Services Task Force, et al. JAMA. 2022 Aug 23; 328(8):746-53.

16. Zoungas S, Curtis A, Spark S, et al. BMJ Open. 2023 Apr 3; 13(4):e069915.

17. Bonnet F, Benard A, Poulizac P, et al. Trials. 2020; 21:342.

Authors do not have any conflicts of interest to declare.