Association of statin use in older people primary prevention group with risk of cardiovascular events and mortality: a systematic review and meta-analysis of observational studies

Abstract

Background Current evidence from randomized controlled trials on statins for primary prevention of cardiovascular disease (CVD) in older people, especially those aged > 75 years, is still lacking. We conducted a systematic review and meta-analysis of observational studies to extend the current evidence about the association of statin use in older people primary prevention group with risk of CVD and mortality. Methods PubMed, Scopus, and Embase were searched from inception until March 18, 2021. We included observational studies (cohort or nested case-control) that compared statin use vs non-use for primary prevention of CVD in older people aged ≥ 65 years; provided that each of them reported the risk estimate on at least one of the following primary outcomes: all cause-mortality, CVD death, myocardial infarction (MI), and stroke. Risk estimates of each relevant outcome were pooled as a hazard ratio (HR) with a 95% confidence interval (CI) using the random-effects meta-analysis model. The quality of the evidence was rated using the GRADE approach. Results Ten observational studies (9 cohorts and one case-control study; n = 815,667) fulfilled our criteria. The overall combined estimate suggested that statin therapy was associated with a significantly lower risk of all-cause mortality (HR: 0.86 [95% CI 0.79 to 0.93]), CVD death (HR: 0.80 [95% CI 0.78 to 0.81]), and stroke (HR: 0.85 [95% CI 0.76 to 0.94]) and a non-significant association with risk of MI (HR 0.74 [95% CI 0.53 to 1.02]). The beneficial association of statins with the risk of all-cause mortality remained significant even at higher ages (> 75 years old; HR 0.88 [95% CI 0.81 to 0.96]) and in both men (HR: 0.75 [95% CI: 0.74 to 0.76]) and women (HR 0.85 [95% CI 0.72 to 0.99]). However, this association with the risk of all-cause mortality remained significant only in those with diabetes mellitus (DM) (HR 0.82 [95% CI 0.68 to 0.98]) but not in those without DM. The level of evidence of all the primary outcomes was rated as “very low.” Conclusions Statin therapy in older people (aged ≥ 65 years) without CVD was associated with a 14%, 20%, and 15% lower risk of all-cause mortality, CVD death, and stroke, respectively. The beneficial association with the risk of all-cause mortality remained significant even at higher ages (> 75 years old), in both men and women, and in individuals with DM, but not in those without DM. These observational findings support the need for trials to test the benefits of statins in those above 75 years of age.

PoLA/CFPiP/PCS/PSLD/PSD/PSH guidelines on diagnosis and therapy of lipid disorders in Poland 2021

“…However, it should be noted that also in this analysis, individuals in secondary prevention comprised a majority [ 364 ]. A valuable supplement to the results discussed above is the latest meta-analysis of 10 observational studies which included over 815,000 patients aged over 65 years in primary prevention [ 365 ]. This analysis is the more valuable because in randomised trials primarily composite endpoints are assessed rather than the effect of a specific therapy on the components of these endpoints; usually, the number of elderly patients is very limited, not to mention the follow-up duration, usually up to 5 years (in this analysis, the follow-up ranged from 5 to 24 years) [ 365 ].…”

“…A valuable supplement to the results discussed above is the latest meta-analysis of 10 observational studies which included over 815,000 patients aged over 65 years in primary prevention [ 365 ]. This analysis is the more valuable because in randomised trials primarily composite endpoints are assessed rather than the effect of a specific therapy on the components of these endpoints; usually, the number of elderly patients is very limited, not to mention the follow-up duration, usually up to 5 years (in this analysis, the follow-up ranged from 5 to 24 years) [ 365 ]. The authors demonstrated that statin therapy in the elderly was associated with a significant 14% reduction in all-cause mortality, a 20% reduction in cardiovascular mortality, a 15% reduction in stroke, and a 26% numerical reduction (not statistically significant) in the risk of myocardial infarction.…”

“…The authors demonstrated that statin therapy in the elderly was associated with a significant 14% reduction in all-cause mortality, a 20% reduction in cardiovascular mortality, a 15% reduction in stroke, and a 26% numerical reduction (not statistically significant) in the risk of myocardial infarction. Importantly, this significant effect (reduction of all-cause mortality) was maintained regardless of age, also in patients > 75, > 80, and > 85 years of age (risk reduction of 12, 16, and 12%, respectively), in both women and men, but mainly in individuals with diabetes (18% risk reduction) [ 365 ].…”

Cardiovascular Risk Factors and Physical Activity for the Prevention of Cardiovascular Diseases in the Elderly

“…Regarding lipid-lowering agents, a body of evidence suggested that statins administered for primary prevention in patients aged 65 to 74 years (with hypertension and moderate dyslipidemia) do not confer any benefits, and in patients over 75 years, the benefits are insignificant [ 94 ]. However, a 2021 systematic review conducted by Awad et al concluded that statin use in older adults aged ≥65 years was associated by a 14% lower risk for mortality (all-cause) and a 20% reduction of the risk of cardiovascular death [ 95 ].…”

Statin Therapy in Very Old Patients: Lights and Shadows

“…Statin therapy was associated with a significantly lower risk of all-cause mortality (HR: 0.86 [95% CI 0.79–0.93]), ASCVD death (HR: 0.80 [95% CI 0.78–0.81]), and stroke (HR: 0.85 [95% CI 0.76–0.94]) and a non-significant association was found with risk of MI (HR 0.74 [95% CI 0.53–1.02]). The beneficial association of statins on the risk of all-cause mortality remained significant even among older individuals (>75 years old; HR 0.88 [95% CI 0.81–0.96]) ( 55 ).…”