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 | Maged Mohammed | Mahmoud Mohamed Zaki | Abdelrahman I. Abushouk | Gregory Y. H. Lip | Michael J. Blaha | Carl J. Lavie | Peter P. Toth | J. Wouter Jukema | Naveed Sattar & Maciej Banach on behalf of the Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group and the International Lipid Expert Panel (ILEP)

First published: |



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.


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.


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.”


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.

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Authors’ contributions

Conceptualization: Kamal Awad, Maciej Banach; Data curation: Kamal Awad, Maged Mohammed, Mahmoud Mohamed Zaki; Formal analysis: Kamal Awad, Maciej Banach; Methodology: Kamal Awad, Maged Mohammed, Mahmoud Mohamed Zaki, Maciej Banach; Project administration: Maciej Banach; Writing – original draft: Kamal Awad, Maged Mohammed, Mahmoud Mohamed Zaki; Writing – review and editing: Kamal Awad, Maged Mohammed, Mahmoud Mohamed Zaki, Abdelrahman I. Abushouk, Gregory Y. H. Lip, Michael J. Blaha, Carl J. Lavie, Peter P. Toth, J. Wouter Jukema, Naveed Sattar, Maciej Banach. The authors read and approved the final manuscript.



Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.


Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
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. 
Author details 
1 Faculty of Medicine, Zagazig University, Zagazig, Egypt.
2 Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
3 Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK.
4 The Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD, USA.
5 John Ochsner Heart and Vascular Institute, Ochsner Clinical School-the University of Queensland School of Medicine, New Orleans, LA, USA.
6 Preventive Cardiology, CGH Medical Center, Sterling, IL, USA.
7 Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands and Netherlands Heart Institute, Utrecht, the Netherlands.
8 Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
9 Head Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz (MUL), Lodz, Poland.
10 Polish Mother’s Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.
11 Cardiovascular Research Centre, University of Zielona Gora, Zielona Gora, Poland.

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