Table 2.

Studies examining statins for primary prevention in older adults since 2016

Study	Population age	Dose of statin	Outcomes	Effect estimate (95% CI); p value	Conclusion	Study limitations
Analyses of randomized controlled trials
Ridker et al. [13]
Meta-analysis:   HOPE-3 and JUPITER   N = 30,507   Median follow-up:   6 years (H3), 2 years (J)	N = 13,517 age < 65 years N = 8208 age 65–69 years N = 8781 age ≥ 70 years Mean age: 66 years	Rosuvastatin 10 mg (H3, N = 6361) Rosuvastatin 20 mg (J, N = 8901) vs. placebo (N = 15,245)	Pooled estimates of ASCVD eventsa Age < 65 years Age 65–69 years Age ≥ 70 years	Hazard ratios: 0.75 (0.57–0.97) 0.51 (0.38–0.69) 0.74 (0.61–0.91)	Statin use associated with a significant lower risk of pooled ASCVD events from both trial groups, regardless of age	Few participants > 75 years
Han et al. [2]
Post hoc analysis:   ALLHAT-LLT   N = 2867   Mean follow-up: 5 years	N = 2141 age 65–74 years N = 726 age ≥ 75 years Median age: 71 years	Pravastatin 40 mg daily (N = 1467) vs. usual care (N = 1400)	All-cause mortality Age 65–74 years Age ≥ 75 years CVD deaths Age 65–74 years Age ≥ 75 years CHD deaths Age 65–74 years Age ≥ 75 years Stroke deaths Age 65–74 years Age ≥ 75 years	Hazard ratios: 1.18 (0.97–1.42); 0.09 1.08 (0.85–1.37); 0.55 1.34 (0.98–1.84); 0.07 1.14 (0.86–1.52); 0.36 1.02 (0.72–1.45); 0.91 1.39 (0.84–2.32); 0.20 0.97 (0.65–1.44); 0.87 0.94 (0.58–1.51); 0.79 0.99 (0.49–2.00); 0.97 1.36 (0.67–2.78); 0.40 1.08 (0.46–2.54); 0.87 2.27 (0.59–8.79); 0.23	No benefit for all-cause mortality or CHD events in the statin group, nonsignificant trend toward increased all-cause mortality observed in those aged ≥ 75 years in the statin group	High rates of crossover between the placebo and intervention groups, leading to minimal LDL-C differences between groups Participants initially started on low-dose pravastatin and titrated upward, a method that was changed mid-study
Retrospective cohort study
Orkaby et al. [9]
Retrospective analysis:   Physicians’ Health Study   N = 2260   Median follow-up: 7 years	N = 1174 age 70–76 years N = 796 age ≥ 76 years Median age: 77 years	Any dose of statin taken for ≥ 181 days in the past year vs. statin < 181 days (N = 1130 matched pairs)	Major CV eventsb All-cause mortality CHD onlyc Stroke onlyd	Hazard ratios: 0.86 (0.70–1.06); 0.17 0.82 (0.69–0.98); 0.03 0.95 (0.74–1.21); 0.66 0.70 (0.45–1.09); 0.12	Statin use associated with a significant lower risk of mortality in older male physicians ≥ 70 years of age, nonsignificant lower risk of CVD events	Unmeasured confounding due to the retrospective design
Huesch [33]
SPRINT N = 3019 Median follow-up: 3 years	N = 3054 age ≥ 70 years Median age: 77 years	Any dose of statin (N = 1334) vs. no statin (N = 1685)	Primary composite event rate reductione Time reduction to composite eventf	Absolute risk reductions: 0.018 (−0.005 to 0.040); 0.13 84.6 (−50.7 to 220.0); 0.22	In those aged ≥ 70 years, no significant difference in the primary composite event rate Nonsignificantly faster time to event in the statin user group; this persisted when the age was lowered to ≥ 65 years	Unmeasured confounding due to the retrospective design Original trial did not randomize based on statins vs. none
Ramos et al. [11]
Catalan, Spain   Primary care system data   N = 46,864   Median follow-up: 8 years	N = 38,557 age 75–84 years N = 8307 age ≥ 85 years Median age: 77 years	Any dose of statin (N = 7502) vs. no statin (N = 39,362), grouped by the presence of DMII vs. none	Incidence of ASCVD DMII statin vs. none	Hazard ratios:	No significant reduction in ASCVD or all-cause mortality in patients aged ≥ 75 years without DMII For diabetic patients aged ≥ 75 years, statin use was associated with significant reductions in ASCVD and all-cause mortality; this decreased after age 85 years and disappeared in nonagenarians	Unmeasured confounding due to the retrospective design Few participants aged ≥ 85 years taking statins, limiting power to detect benefit in this age group
			Age 75–84 years	0.76 (0.65–0.89)
			Age ≥ 85 years	0.82 (0.53–1.26)
			No DMII statin vs. none
			Age 75–84 years	0.98 (0.91–1.05)
			Age ≥ 85 years	0.93 (0.82–1.06)
			All-cause mortality DMII statin vs. none
			Age 75–84 years	0.84 (0.75–0.94)
			Age ≥ 85 years	1.05 (0.86–1.28)
			No DMII statin vs. none
			Age 75–84 years	0.94 (0.86–1.04)
			Age ≥ 85 years	0.97 (0.90–1.05)
Bezin et al. [34]
French health Insurance system data   N = 7286   Median follow-up: 5 years	All participants aged ≥ 75 years Median age: 80 years	Statin new userg vs. nonuser, grouped by: primary prevention with modifiable risk factorsh, and primary prevention without modifiable risk factors (N = 3642 matched pairs)	Incidence of ACS or all-cause mortality Primary risk factors Primary without	Hazard ratios: 0.93 (0.89–0.96); < 0.01 1.01 (0.86–1.18); 0.92	Statin use significantly associated with lower risk of ACS or all-cause mortality in primary prevention with modifiable risk factors No significant difference in primary prevention without modifiable risk factors	Unmeasured confounding due to the retrospective design
Kim et al. [32]
Cardiology outpatients   Seoul, Korea   N = 1559   Median follow-up: 5 years	All participants aged > 75 years Median age: 78 years	New users of statins (took statins during > 80% of the follow-up period) vs. nonuser (N = 639 matched pairs)	Cumulative incidence of MACCEi Cumulative all-cause mortality	Hazard ratios: 0.59 (0.41–0.85); 0.005 0.56 (0.34–0.93); 0.024	Statin use was significantly associated with a lower risk of CV events and all-cause death	Unmeasured confounding due to the retrospective design Low event rate due to the sample size

CI confidence interval, H3 Hope-3 Trial, J Jupiter trial, ASCVD atherosclerotic cardiovascular disease, ALLHAT-LLT Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, CVD cardiovascular disease, CHD coronary heart disease, SPRINT Systolic Blood Pressure Intervention Trial, DMII diabetes mellitus type II, MACCE major adverse cardiovascular and cerebrovascular events, LDL-C low-density lipoprotein-cholesterol, ACS acute coronary syndrome

^aNonfatal myocardial infarction, nonfatal stroke, or cardiovascular death

^bMyocardial infarction, mortality from myocardial infarction, stroke, mortality from stroke, coronary artery bypass graft or percutaneous intervention

^cMyocardial infarction, mortality from myocardial infarction, coronary artery bypass graft or percutaneous intervention

^dStroke or mortality from stroke

^eComprising myocardial infarction, other acute coronary syndrome, stroke, heart failure, or cardiovascular-related death

^fA reduction in time to event implies a higher hazard rate

^gNew user was defined as a first-identified patient dispensed a statin who had not been dispensed a statin in the previous year

^hPrimary prevention with modifiable risk factors included participants without a history of coronary heart disease but with at least one of the following: diabetes, dispensing of antihypertensive drugs, antiplatelet agents, or anticoagulants

ⁱComposite outcome of cardiovascular death, nonfatal myocardial infarction, coronary revascularization, and nonfatal ischemic stroke or transient ischemic attack