The average 80-year-old in the trial was taking five medications before anyone randomized them. That number, buried in the baseline characteristics of the SAGA/SITE study published this week in The Lancet Healthy Longevity, is the quiet engine behind a question that has divided cardiologists for a decade: when, if ever, is it safe to stop a statin?
The trial’s headline answer, reported in a healthy French population of 1,180 adults aged 75 and older with no history of cardiovascular disease, is reassuring: stopping the cholesterol-lowering drugs did not increase deaths over three years. Mortality was 7.2 percent among those who stopped versus 7.9 percent among those who continued, a difference that met the pre-specified threshold for non-inferiority. But the study is small, short, and underpowered, and the cardiologists asked to interpret it are nearly unanimous that it should not be read as a license to tear up prescriptions.
What the trial actually did
SAGA/SITE, which stands for Statins In The Elderly, is a multicenter, open-label, pragmatic, non-inferiority randomized trial run across 297 primary care practices in France. Between 2016 and 2020, researchers enrolled adults aged 75 or older who had been taking a statin for at least a year for primary prevention, meaning they had never had a heart attack, stroke, or other atherosclerotic event. Participants were randomized in a 5:4 ratio to either continue their statin or stop it, and followed for 36 months.
The primary endpoint was all-cause mortality at three years, with a non-inferiority margin of 5 percentage points. The result: 35 of 484 who stopped (7.2 percent) died versus 48 of 604 who continued (7.9 percent), an absolute difference of minus 0.68 percentage points with a confidence interval whose upper bound, 2.60 percent, stayed comfortably inside the margin. The composite of death or major cardiovascular events was also non-inferior, at 12.0 percent versus 11.4 percent.
What happened to their cholesterol was dramatic and immediate. In the discontinuation group, LDL cholesterol rose from a mean of 114.6 to 170.6 mg/dL within three months, an increase of roughly 50 percent, while total cholesterol climbed from 199 to 257 mg/dL. The continued group saw no change. The trial’s authors, led by Fabrice Bonnet of the University Hospital of Bordeaux, frame the finding as support for individualized decision-making: patients should talk to their doctors about whether they would be no worse off dropping the daily pill.
The trial fills a genuine gap. The randomized evidence for statins was built mostly on middle-aged populations; the link between cholesterol and cardiovascular events, as the authors note, weakens with age, and older adults accumulate competing risks, frailty, and polypharmacy. Deprescribing has become a clinical movement of its own, driven by the recognition that each additional daily pill carries costs, side effects, and interactions. Against that backdrop, a trial suggesting that stopping is safe could shift the default.
The authors are careful about their own limits. They note the study needs to be repeated with longer follow-up and extended to populations at higher cardiovascular risk or in poorer health. They also point to a curious secondary finding: stopping produced no measurable improvement in quality of life. SF-12 physical and mental scores were identical between groups at three years. For patients hoping to shed a pill and feel better, the trial offers no such payoff.
Why experts are pushing back
The reaction from the cardiology community, collected by the Science Media Centre, is notably sharper than the paper’s own conclusions. Bryan Williams, chief scientific and medical officer of the British Heart Foundation, called the trial modest, with roughly 1,100 participants, an average age of 80, and a majority of women, and warned it must not be read as evidence that statins no longer benefit older people. Decades of evidence, including meta-analyses of trials that included older patients, show the drugs save lives, he said, and the findings do not apply to secondary prevention, where the drugs are most clearly life-saving.
Robert Storey of the University of Sheffield listed five limitations: the trial is too small and too short, heart attacks were numerically more common among those who stopped (2.1 versus 1.4 percent), more than half the participants were over 80 with high competing mortality, stopping produced no quality-of-life or symptom benefit, and recruitment difficulties mean participants may not represent typical over-75s. He concluded the results have very limited applicability and carry a risk of promoting statin cessation in people who might benefit.
Others are blunter about the statistics. Borislava Mihaylova of Oxford called the trial substantially underpowered and said it should not inform clinical decision-making. Carlos Guijarro of the Spanish Society of Arteriosclerosis noted the study’s statistical power fell from an anticipated 90 percent to under 50 percent, on a par with flipping a coin, and contrasted it with a Lancet meta-analysis of 186,000 patients, including about 14,000 over 75, showing consistent benefit from statins, and with observational studies from Denmark and Italy linking discontinuation to roughly 30 percent higher cardiovascular morbidity and mortality.
Changing the conversation, not the default
The Lancet-commissioned commentary accompanying the paper makes the same point in its title: this trial changes the conversation, not the default. The commentary’s authors argue the most clinically informative finding is not that stopping was safe, but that stopping produced no patient-centered benefit, no improvement in quality of life, cognition, function, or symptoms. Deprescribing, in other words, is not inherently beneficial, and routine discontinuation is not justified.
The trial also underlines a structural problem in geriatric medicine: the people for whom polypharmacy is most acute are the people for whom the evidence is thinnest. SAGA/SITE planned to enroll 2,430 participants and managed 1,180, a shortfall that limited its power and its subgroups. Larger trials are underway, including STREAM in Europe and PREVENTABLE in the United States, which may take years to report.
For now, the practical guidance from every major voice in this debate is the same: patients over 75 should not stop statins on their own, and doctors should not reflexively discontinue them, but the question now has a randomized answer worth discussing at the next appointment. The trial did not prove that stopping is harmful, and it did not prove it helps. It proved that the question deserves to be asked out loud.
Sources
1. Fabrice Bonnet, Pierre Poulizac, Nicolas Rousselot, et al., “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,” The Lancet Healthy Longevity (2026), published online August 11, 2026. DOI: 10.1016/j.lanhl.2026.100884. PMID: 42580354.
2. Elizabeth Cooney, “Stopping statins in people over 75 at low risk for heart disease didn’t increase deaths,” STAT News, August 11, 2026. https://www.statnews.com/2026/08/11/stop-statins-age-75-lancet-study-suggests-safe-healthy-adults/
3. Science Media Centre, “Expert reaction to discontinuation of statins for primary prevention… in adults 75 or older,” August 11, 2026. https://www.sciencemediacentre.org/expert-reaction-to-discontinuation-of-statins-for-primary-prevention-of-atherosclerotic-cardiovascular-disease-in-adults-75-or-older/
4. Arya Nezhad, Parvaneh Rastgou, Michael G. Nanna, “Statin discontinuation in older adults: changing the conversation, not the default,” The Lancet Healthy Longevity (2026), DOI: 10.1016/j.lanhl.2026.100888.
5. SITE study protocol, BMC Trials (open access). https://pmc.ncbi.nlm.nih.gov/articles/PMC7169009
6. PubMed record: https://pubmed.ncbi.nlm.nih.gov/42580354/