A Recent Review Regarding the Use of Statins in Elderly People

PROSPER trial included elderly subjects aged 70-82 years with a history of vascular disease or risk factors to pravastatin or placebo. Primary endpoint was reduced in 15% in statin group. Risk reduction seemed more pronounced in secondary than in primary prevention. However, testing for interaction revealed no significant differences between these subgroups [2]. Using high-sensitivity C-reactive protein ≥2mg/L to predict cardiovascular events, the JUPITER trial revealed a significant reduction in MACE, stroke, revascularization in ≥65 years old population with high-intensity statin as a primary prevention therapy [3]. A metanalyses from HOPE-3 and JUPITER trials demonstrated a 26% relative risk reduction for the end point of nonfatal MI, nonfatal stroke or cardiovascular death in people ≥ 70 years using statins in primary prevention [4].
Cholesterol Treatment Trialists’ Collaboration metanalysis from 28 randomized controlled trials showed 13% reduction (HR 0.87, CI95% 0.77-0.99) in major vascular events in subjects >75 years comparing statin or more intensive treatment versus control or less intensive. Interestingly that among subjects with vascular disease the reduction in major vascular events were similar between younger and older subjects. In the other hand, among those with no history of vascular disease, there was a trend towards smaller proportional risk reductions with increasing age [5]. This metanalysis reported beneficial effects in secondary prevention, but it is less clear the benefits for primary prevention.
A recently published post hoc analysis of the ASPREE trial showed that the use of statins in individuals ≥70 years with no evidence of CVD, dementia or physical disability, significantly reduced MACE, risk for persistent physical disability, MI and stroke. The outcomes began to be seen in the first year of follow-up [6]. These findings may give strength to use statins in primary prevention and also alleviate the concerns about safety of statins in older people. EWTOPIA 75 trial revealed a significant reduction in coronary revascularization in patients ≥75 years with no CVD using a moderate-intensity cholesterol treatment with addition of ezetimibe 10 mg. However, there was no difference in MI or stroke [7]. Orkaby et al. [8] in a retrospective cohort study showed significant reduction in all-cause mortality and cardiovascular death within 2 to 5 years of follow-up in ≥ 75 years old patients free of atherosclerotic cardiovascular disease at baseline, even in people ≥ 90 years old [8].
Prior studies found that statins were not associated with impaired quality of life, frailty or increased risk of myopathy, but regardless, physicians need to be very careful when prescribing new drugs in elderly people, since they are more susceptible and less tolerant to side effects. Life expectancy, comorbidities, drug interaction and quality of life must also be taken into account. As the population ages due to the increase in life expectancy, a necessity to understand the real benefits and safety of lipid-lowing drugs in older population is needed. Cholesterol blood management guidelines usually recommend evaluating CVD risk and start statin in patients considered high risk or intermediate risk with risk enhancers [9]. Elderly subjects usually are at least intermediate to high risk only due to chronological age. In this way, decision about cholesterol treatment in this population should also include biomarkers of subclinical atherosclerosis and life expectancy since their benefit starts after a mean of 2 years of follow-up. The benefit of statin in reducing new cardiovascular events are robust in secondary prevention, especially in coronary artery disease and stroke, so its use should be encouraged, even in older population. Further randomized clinical trials are needed to determine the role of statin therapy in primary prevention elderly subjects specially those >75 years old.

1. Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, et al. (2007) 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 370(9602): 1829-1839.
2. Shepherd J, Blauw GJ, Murphy MB, Bollen ELEM, Buckley BM, et al. (2002) Pravastatin in elderly individuals at risk of vascular disease (PROSPER): A randomised controlled trial. Lancet 360(9346): 1623-1630.
3. Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, et al. (2008) Rosuvastatin to prevent vascular events in men and women with elevated c-reactive protein. N Engl J Med 359(21): 2195-2207.
4. Ridker PM, Lonn E, Paynter NP, Glynn R, Yusuf S (2017) Primary prevention with statin therapy in the elderly, new meta-analyses from the contemporary jupiter and hope-3 randomized trials. Circulation 135(20): 1979-1981.
5. Fulcher J, Baigent C, Barnes E, Betteridge DJ, Blackwell L, et al. (2019) Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Lancet 393(10170): 407-415.
6. Zhou, Asenso RO, Curtis AJ, Breslin M, Wolfe R, et al. (2020) Association of statin use with disability free survival and cardiovascular disease among healthy older adults. Journal of the American College of Cardiology 76(1): 17-27.
7. Yasuyoshi O, Sasaki J, Arai H, Yokote K, Haradaet K, et al. (2019) Ezetimibe lipid-lowering trial on prevention of atherosclerotic cardiovascular disease in 75 or older (Ewtopia 75): a randomized, controlled trial. Circulation 140(12): 992-1003.
8. Orkaby AR, Driver JA, Ho YL, Bing L, Costa L, et al. (2020) Association of statin use with all-cause and cardiovascular mortality in us veterans 75 years and older. JAMA 324(1): 68-78.
9. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, et al. (2018) Guideline on the management of blood cholesterol. a report of the american college of cardiology/american heart association task force on clinical practice guidelines. Journal of the American College of Cardiology 73(24): 3168-3209.