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Meta-Analysis
.2021 Jun 22;19(1):139.
doi: 10.1186/s12916-021-02009-1.

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

Affiliations
Meta-Analysis

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

Kamal Awad et al. BMC Med..

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.

Keywords: Mortality; Myocardial infarction; Older; Primary prevention; Statins; Stroke.

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Conflict of interest statement

Gregory Y. H. Lip: consultant for Bayer/Janssen, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo; speaker for BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are directly received personally; Michael J. Blaha: grants; FDA, NIH, AHA, Aetna Foundation, Amgen Foundation; advisory board/consultant; Amgen, Sanofi, Regeneron, Kowa, Novartis, Novo Nordisk, Bayer, 89Bio, Akcea, Gilead; Carl J. Lavie: speaker and consultant for Regeneron, Sanofi, Amgen, and Esperion on non-statin lipid medications; Peter P. Toth: speakers bureau; Amarin, Amgen, Esperion, Novo-Nordisk; consultant; Amarin, Amgen, bio 89, Kowa and Novartis; J. Wouter Jukema/his department has received research grants from and/or was a speaker (with or without lecture fees) on a.o.(CME accredited) meetings sponsored by Amgen, Athera, Astra-Zeneca, Biotronik, Boston Scientific, Dalcor, Daiichi Sankyo, Lilly, Medtronic, Merck-Schering-Plough, Pfizer, Roche, Sanofi Aventis, The Medicine Company, the Netherlands Heart Foundation, CardioVascular Research the Netherlands (CVON), the Netherlands Heart Institute and the European Community Framework KP7 Programme; Naveed Sattar has consulted for Amgen, Astrazeneca, Boehringer Ingelheim, Eli-Lilly, MSD, Novo Nordisk, Pfizer and Sanofi, and received Grant income from Boehringer Ingelheim; Maciej Banach: speakers bureau; Abbott/Mylan, Abbott Vascular, Actavis, Akcea, Amgen, Biofarm, KRKA, MSD, Polpharma, Sanofi-Aventis, Servier and Valeant; consultant to Abbott Vascular, Akcea, Amgen, Daichii Sankyo, Esperion, Freia Pharmaceuticals, Lilly, MSD, Polfarmex, Resverlogix, Sanofi-Aventis; Grants from Sanofi and Valeant; Kamal Awad, Maged Mohammed, Mahmoud Mohamed Zaki, and Abdelrahman I. Abushouk have no conflict of interest.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram of study screening and selection. LLT, lipid-lowering treatment; OR, odds ratio; HR, hazard ratio; CHD, coronary heart disease; CVD, cardiovascular disease. *No additional eligible studies were found by manual search
Fig. 2
Fig. 2
Forest plots displaying the results of the meta-analysis of observational studies that compared statin use with non-use in older people aged ≥ 65 years and without cardiovascular disease—A in terms of all-cause mortality andB in terms of cardiovascular death. HR, hazard ratio; CI, confidence interval; CV, cardiovascular
Fig. 3
Fig. 3
Forest plot displaying the results of the meta-analysis of observational studies that compared statin use with non-use in older people aged ≥ 65 years and without cardiovascular disease in terms of stoke. HR, hazard ratio; CI, confidence interval
Fig. 4
Fig. 4
Forest plots displaying the results of the meta-analysis of observational studies that compared statin use with non-use in older people aged ≥ 65 years and without cardiovascular disease in terms of myocardial infarction—A before removing the study by Jun et al. andB after removing the study by Jun et al. HR, hazard ratio; CI, confidence interval; MI, myocardial infarction
Fig. 5
Fig. 5
Forest plot displaying the results of the subgroup analysis (according to age, sex, diabetes mellitus, and risk of bias) of observational studies that compared statin use with non-use in older people aged ≥ 65 years and without cardiovascular disease in terms of all-cause mortality. HR, hazard ratio; HCI, higher confidence interval; LCI, lower confidence interval. *Number of included participants. **The exact number of statin users in the study by Lemaitre et al. was not reported and not added to the presented number
See this image and copyright information in PMC

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