Age and primary prevention of CHD

• treatment benefits with statins in CHD appear similar in women and men - these benefits are independent of age up to 75 years (1,2)
  
  
• evidence relating to the benefit of treating older patients has been provided by the MRC/BJF Heart Protection Study - this study provides evidence of reductions of at least one-third in major vascular events applied in groups where benefit had previously been uncertain such as people aged over 70, women, younger age groups, stroke patients, people with total cholesterol levels below 5 mmol/l (200mg/dl) or LDL-C below 3mmol/l (120mg/dl) (3)
  
  
• a meta-analysis of 24,674 subjects (42.7% females; mean age 73.0 ± 2.9 years; mean follow up 3.5 +/- 1.5 years) in primary prevention showed (4)
  • statins, compared with placebo, significantly reduced the risk of MI by 39.4% (relative risk [RR]: 0.606 [95% confidence interval (CI): 0.434 to 0.847]; p = 0.003) and the risk of stroke by 23.8% (RR: 0.762 [95% CI: 0.626 to 0.926]; p = 0.006)
  • however, the risk of all-cause death (RR: 0.941 [95% CI: 0.856 to 1.035]; p = 0.210) and of CV death (RR: 0.907 [95% CI: 0.686 to 1.199]; p = 0.493) were not significantly reduced
  • the authors concluded that "..in elderly subjects at high CV risk without established CV disease, statins significantly reduce the incidence of MI and stroke, but do not significantly prolong survival in the short-term..."..but noted that " . current analysis was based on aggregate and not on patient-level data. In addition, only 2 studies included in the meta-analysis were designed to enroll elderly patients, whereas the majority of patients included represent elderly subgroups of clinical trials.."
    
    
• a study followed patients aged 65years or older who were eligible for primary cardiovascular prevention for a period of 10years (5):
  • analysis included 19,518 older adults followed during 10years (median = 9.7 y). All-cause mortality rates were 34% lower among those who had adhered to statin treatment, compared with those who had not (hazard ratio [HR] = 0.66; 95% confidence interval [CI] = 0.56-0.79)
    • adherence to statins was also associated with fewer atherosclerotic cardiovascular disease events (HR = 0.80; 95% CI = 0.71- 0.81). The benefit of statin use did not diminish among beyond age 75 and was evident for both women and men
  • study authors concluded that adherence to statins may be associated with reduced mortality and cardiovascular morbidity among older adults, regardless of age and sex
    
    
• Copenhagen General Population Study (CGPS) (6)
  • study data was obtained from 91,131 individuals enrolled between November 2003 and February 2016. This cohort reflects the Danish general population aged 20-100 years
  • participants did not have ASCVD or diabetes at baseline and were not taking statins
  • risk of MI (fatal and non-fatal) and ASCVD (MI, fatal coronary heart disease, and non-fatal or fatal ischemic stroke) per 1.0 mmol/L increase in LDL-c was determined in the overall population and stratified by age groups (20–49, 50–59, 60–69, 70–79, and 80–100 years)
  • MI and ASCVD event rates per 1000 person-years increased with higher LDL-c and older age, with highest event rates in individuals aged 80-100 years and LDL-c >=5 mmol/L (13.2 MI events per 1000 person-years and 37.1 ASCVD events per 1000 person years)
  • The NNT in 5 years to prevent one ACVD event event was 42 in the 80–100 years age group, 88 in the 70–79 years group, 164 in the 60–69 years group, 345 in the 50–59 years group, and 769 in the 20–49 years group
  • study authors concluded that people aged 70–100 years with elevated LDL cholesterol had the highest absolute risk of myocardial infarction and atherosclerotic cardiovascular disease and the lowest estimated NNT in 5 years to prevent one event
    
    
• NICE state that (7):
  • use the QRISK3 risk assessment tool to assess CVD risk for the primary prevention of CVD in people up to and including age 84 years
  • offer atorvastatin 20 mg for the primary prevention of CVD to people who have a 10% or greater 10-year risk of developing CVD
    
    
• a review of the evidence suggests that benefit of statins in primary prevention for patients older than 80 years is not certain (8)
  • this review contrasts with the CGPS study which concluded that people aged 70-100 years with elevated LDL cholesterol had the highest absolute risk of myocardial infarction and atherosclerotic cardiovascular disease and the lowest estimated NNT in 5 years to prevent one event (6)
  • there seems no controversy in initiation of statins in patients for primary prevention up to 80 years of age
    
    
• effectiveness of statins with respect to age
  • low- to moderate-intensity statins were associated with greater mean LDL-C reductions in those>=75 years than in those <50 (e.g. 39.0% v 33.8% for simvastatin 20mg; 44.2% v 40.2% for atorvastatin 20mg) (9)

Evidence for greater CV risk benefit for statin treatment in patients >= 85 years old versus those 75-84 years old (10)

• study found that among older adults aged 75-84, initiation of statin therapy led to a 1.2% risk reduction in major CVD over a 5-year period
  • for older adults aged 85 and greater, initiation of statins had an even larger impact, leading to a 4.4% risk reduction in major CVD over a 5-year period

Elderly people are at highest risk of cardiovascular morbidity and mortality, and so have much to gain from the appropriate management of risk factors such as hyperlipidaemia. The beneficial effects of statins may not be due to cholesterol lowering alone - factors such as plaque stabalization may also play a role.

Reference:

• (1) LaRosa JC et al (1999). Effects of statins on risk of coronary disase. A meta-analysis of randomized controlled trials. JAMA, 282, 2340-6.
• (2) Sacks FM et al (2000). Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors. The prospective pravastatin pooling project. Circulation, 102, 1893-1900.
• (3) MRC/BHF Heart Protection Study: preliminary results.Int J Clin Pract 2002, Jan-Feb 56(1), 53-6
• (4) Savarese G et al. Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis.J Am Coll Cardiol. 2013;62(22):2090-9.
• (5) Ramos 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 Sep 5;362:k3359
• (6) Mortensen MB & Nordestgaard BG. Elevated LDL cholesterol and increased risk of myocardial infarction and atherosclerotic cardiovascular disease in individuals aged 70-100 years: a contemporary primary prevention cohort. Lancet. 2020 Nov 21;396(10263):1644-1652. doi: 10.1016/S0140-6736(20)32233-9.
• (7) NICE (May 2023). Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease
• (8) Marcellaud E, Jost J, Tchalla A, Magne J, Aboyans V. Statins in Primary Prevention in People Over 80 Years. Am J Cardiol. 2023 Jan 15;187:62-73.
• (9) Corn A et al. Association Between Age and Low-Density Lipoprotein Cholesterol Response to Statins: A Danish Nationwide Cohort Study. Ann Intern Med. [Epub 1 August 2023]. doi:10.7326/M22-2643
• (10) Xu W et al. et al. Benefits and Risks Associated With Statin Therapy for Primary Prevention in Old and Very Old Adults: Real-World Evidence From a Target Trial Emulation Study. Ann Intern Med.2024;177:701-710.