SAGA/SITE study - discontinuation of statins for primary prevention of atherosclerotic cardiovascular disease in adults aged 75 years or older

Study design:

• 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
• 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

Study 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
• 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
  • 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

Study authors stated:

“..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..”

Reference:

1. Bonnet F et al; SAGA/SITE Study Group. 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. Lancet Healthy Longev. 2026 Jul;7(7):100884.