Discontinuation of statins for primary prevention of atherosclerotic cardiovascular disease in adults aged 75 years or older (SAGA/SITE): a multicentre, open-label, pragmatic, non-inferiority randomised trial
Abstract
BACKGROUND: Statins are among the most widely used drugs; however, their benefits for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in individuals aged 75 years or older without the disease remain uncertain. We aimed to assess the non-inferiority of statin cessation in terms of all-cause mortality under real-life conditions in individuals aged 75 years or older who were prescribed statins for the primary prevention of ASCVD. METHODS: We performed a multicentre, open-label, parallel-group, phase 3 randomised controlled trial in 297 primary care offices. Individuals who were aged 75 years or older, were prescribed any statin for at least 1 year for the primary prevention of ASCVD, had no history of ASCVD, and could provide informed consent were randomly assigned (in an unbalanced 5:4 ratio) to continue or stop their statin treatment and were followed up for 36 months. Participants were excluded if they had a progressive disease with a life expectancy of 3 months or less, were diagnosed with dementia, had known homozygous or double heterozygous familial hypercholesterolaemia, or were unable to provide informed consent. Randomisation was computer-generated and implemented via a central electronic system; masking was not done. The primary endpoint was all-cause mortality at 3 years, analysed in participants according to the primary estimand (participants who met all key eligibility criteria and were randomly assigned to statin discontinuation or continuation less than 90 days after inclusion). Missing data were handled using multiple imputation. The non-inferiority margin was 5% for the absolute between-group difference in mortality. This trial is registered with ClinicalTrials.gov, NCT02547883 (completed). FINDINGS: Between June 15, 2016, and Jan 7, 2020, 1180 participants were randomly assigned, and 1160 participants were included in the analysis of the primary estimand. 639 participants were randomly assigned to the statin continuation group, and 521 participants were assigned to the statin discontinuation group. The median age was 80 years (IQR: 78-84), and 775 (66·8%) of 1160 participants were women; 342 (29·5%) of 1160 participants had diabetes, and 896 (77·2%) of them had hypertension. At 36 months, 48 (7·9%) of 604 participants in the statin continuation group and 35 (7·2%) of 484 participants in the statin discontinuation group had died. The absolute difference in all-cause mortality between groups was -0·68% (95% CI -3·95 to 2·60). Statin discontinuation was non-inferior to continuation for 3-year all-cause mortality as the upper bound of the between group difference 95% CI did not exceed the prespecified non-inferiority margin. Adverse events occurred in 461 (73·1%) of 631 participants in the continuation group, and in 390 (74·0%) of 527 in the discontinuation group. Non-cardiovascular adverse events occurred in 456 (72·3%) of 631 participants in the continuation group and 383 (72·7%) of 527 in the discontinuation group. INTERPRETATION: In persons aged 75 years or older receiving statins for primary prevention and with no previous history of ASCVD, discontinuation of statins was non-inferior to continuation in terms of all-cause mortality over 3 years. These findings support individualised decision-making regarding statin discontinuation in older adults. FUNDING: French Ministry of Health within the framework of the Medico Economical Research Program (PRME) 2014.
Related
- Prevention of SARS-CoV-2 transmission during a large, live, indoor gathering (SPRING): a non-inferiority, randomised, controlled trial
- Protective effects of icariin in atherosclerotic cardiovascular disease: mechanistic basis, post-ischemic protection and translational limitations
- Longitudinal treatment selection under irreversible discontinuation: History-aware prediction and trajectory-aware learning in peanut-allergy prevention
- Revisiting the genetic support of leukotriene pathway drug targets in atherosclerotic cardiovascular disease.
- Impaired CD4+ T cell response to apolipoprotein B-100 peptide P210 in atherosclerotic cardiovascular disease is reversed by P210-conjugated nanoparticles
BibTeX
@article{bonnet2026discontinuation,
title = {{Discontinuation of statins for primary prevention of atherosclerotic cardiovascular disease in adults aged 75 years or older (SAGA/SITE): a multicentre, open-label, pragmatic, non-inferiority randomised trial}},
author = {Fabrice Bonnet and Pierre Poulizac and Nicolas Rousselot and Thierry Couffinhal and Gaël Galli and Driss Berdaï and Marie-Anne Vandenhende and Marine Rousset and Roxane Coueron and Antoine Bénard and Jean-Philippe Joseph and Christophe Adam and Brice Aimé and Brigitte Alexandre and Karim Allaoui and Marc Amendola and Cécile Angoulvant and Pierrick Archambault and Matthieu Ariza and Mickael Asselin and Véronique Athanase and Audrey Atlan-Cottin and Delphine Aubert-Le Grimellec and Pierre Aubois and Anne-Laure Aubriot and Alain Aumarechal and Anne Balere-Jousse and Julie Ballandras and Aurélien Baradel and Jan Baran and Alain Bardoux and Anne Bastien and Veronique Benon and Samy Benzidi and Philippe Beria and Clement Bernard and Olivier Bertaux and Yves Bertin and Jean-Christian Bientz and Arnaud Blanc and Paul Blanchard and François Bloede and Pierre Bobey and Emmanuel Boige and Marie Bord and Jean-Yves Borgne and Ségolène Boucly and Serge Bouhana and Sylvain Bouquet and Odile Bourgeois and Claire Bourgeoisat and Monique Bourges-Duhamel and Claire Bouteville and Philippe Boutin and Céline Bouton and Emilie Boutte and Betty Brayer and Sophie Brenuchot and Nicolas Breton and Séverine Broli},
journal = {The Lancet. Healthy longevity},
year = {2026},
month = aug,
doi = {10.1016/j.lanhl.2026.100884},
url = {https://u-bordeaux.hal.science/hal-05732420v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Discontinuation of statins for primary prevention of atherosclerotic cardiovascular disease in adults aged 75 years or older (SAGA/SITE): a multicentre, open-label, pragmatic, non-inferiority randomised trial
AU - Fabrice Bonnet
AU - Pierre Poulizac
AU - Nicolas Rousselot
AU - Thierry Couffinhal
AU - Gaël Galli
AU - Driss Berdaï
AU - Marie-Anne Vandenhende
AU - Marine Rousset
AU - Roxane Coueron
AU - Antoine Bénard
AU - Jean-Philippe Joseph
AU - Christophe Adam
AU - Brice Aimé
AU - Brigitte Alexandre
AU - Karim Allaoui
AU - Marc Amendola
AU - Cécile Angoulvant
AU - Pierrick Archambault
AU - Matthieu Ariza
AU - Mickael Asselin
AU - Véronique Athanase
AU - Audrey Atlan-Cottin
AU - Delphine Aubert-Le Grimellec
AU - Pierre Aubois
AU - Anne-Laure Aubriot
AU - Alain Aumarechal
AU - Anne Balere-Jousse
AU - Julie Ballandras
AU - Aurélien Baradel
AU - Jan Baran
AU - Alain Bardoux
AU - Anne Bastien
AU - Veronique Benon
AU - Samy Benzidi
AU - Philippe Beria
AU - Clement Bernard
AU - Olivier Bertaux
AU - Yves Bertin
AU - Jean-Christian Bientz
AU - Arnaud Blanc
AU - Paul Blanchard
AU - François Bloede
AU - Pierre Bobey
AU - Emmanuel Boige
AU - Marie Bord
AU - Jean-Yves Borgne
AU - Ségolène Boucly
AU - Serge Bouhana
AU - Sylvain Bouquet
AU - Odile Bourgeois
AU - Claire Bourgeoisat
AU - Monique Bourges-Duhamel
AU - Claire Bouteville
AU - Philippe Boutin
AU - Céline Bouton
AU - Emilie Boutte
AU - Betty Brayer
AU - Sophie Brenuchot
AU - Nicolas Breton
AU - Séverine Broli
PY - 2026
DA - 2026/08/31
JO - The Lancet. Healthy longevity
DO - 10.1016/j.lanhl.2026.100884
UR - https://u-bordeaux.hal.science/hal-05732420v1
AB - BACKGROUND: Statins are among the most widely used drugs; however, their benefits for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in individuals aged 75 years or older without the disease remain uncertain. We aimed to assess the non-inferiority of statin cessation in terms of all-cause mortality under real-life conditions in individuals aged 75 years or older who were prescribed statins for the primary prevention of ASCVD. METHODS: We performed a multicentre, open-label, parallel-group, phase 3 randomised controlled trial in 297 primary care offices. Individuals who were aged 75 years or older, were prescribed any statin for at least 1 year for the primary prevention of ASCVD, had no history of ASCVD, and could provide informed consent were randomly assigned (in an unbalanced 5:4 ratio) to continue or stop their statin treatment and were followed up for 36 months. Participants were excluded if they had a progressive disease with a life expectancy of 3 months or less, were diagnosed with dementia, had known homozygous or double heterozygous familial hypercholesterolaemia, or were unable to provide informed consent. Randomisation was computer-generated and implemented via a central electronic system; masking was not done. The primary endpoint was all-cause mortality at 3 years, analysed in participants according to the primary estimand (participants who met all key eligibility criteria and were randomly assigned to statin discontinuation or continuation less than 90 days after inclusion). Missing data were handled using multiple imputation. The non-inferiority margin was 5% for the absolute between-group difference in mortality. This trial is registered with ClinicalTrials.gov, NCT02547883 (completed). FINDINGS: Between June 15, 2016, and Jan 7, 2020, 1180 participants were randomly assigned, and 1160 participants were included in the analysis of the primary estimand. 639 participants were randomly assigned to the statin continuation group, and 521 participants were assigned to the statin discontinuation group. The median age was 80 years (IQR: 78-84), and 775 (66·8%) of 1160 participants were women; 342 (29·5%) of 1160 participants had diabetes, and 896 (77·2%) of them had hypertension. At 36 months, 48 (7·9%) of 604 participants in the statin continuation group and 35 (7·2%) of 484 participants in the statin discontinuation group had died. The absolute difference in all-cause mortality between groups was -0·68% (95% CI -3·95 to 2·60). Statin discontinuation was non-inferior to continuation for 3-year all-cause mortality as the upper bound of the between group difference 95% CI did not exceed the prespecified non-inferiority margin. Adverse events occurred in 461 (73·1%) of 631 participants in the continuation group, and in 390 (74·0%) of 527 in the discontinuation group. Non-cardiovascular adverse events occurred in 456 (72·3%) of 631 participants in the continuation group and 383 (72·7%) of 527 in the discontinuation group. INTERPRETATION: In persons aged 75 years or older receiving statins for primary prevention and with no previous history of ASCVD, discontinuation of statins was non-inferior to continuation in terms of all-cause mortality over 3 years. These findings support individualised decision-making regarding statin discontinuation in older adults. FUNDING: French Ministry of Health within the framework of the Medico Economical Research Program (PRME) 2014.
SN - 2666-7568
ER -