MUNICH — Atorvastatin reduced the risk of major cardiovascular (CV) events, predominantly nonfatal events, by 30% compared with placebo in adults aged 70 years or older without known cardiovascular disease, diabetes, or dementia in the large randomized STAREE trial.

However, nearly 6 years of treatment did not significantly improve disability-free survival — a composite of death, dementia, or persistent physical disability.

“STAREE is the first large-scale trial of a statin for primary prevention to show cardiovascular benefit in people aged 70 years and older,” lead investigator Sophia Zoungas, MBBS, PhD, of Monash University in Melbourne, Australia, said before her presentation at the European Society of Cardiology (ESC) Congress 2026.

“Whilst we show no benefit on disability-free survival, this remains an important outcome for older people and the purpose of further research,” she noted, adding that “the data also underscore the safety of use of statins in older people.”

The findings address a long-standing evidence gap around starting statins for primary prevention in older adults, who have been underrepresented in previous CV outcome trials. Fewer than one quarter of participants in trials underpinning previous pooled analyses were older than 70 years, Zoungas noted.

The findings were simultaneously published in The New England Journal of Medicine.

Evidence Gap in Older Adults

Statins are well established in reducing myocardial infarction (MI) and ischemic stroke in patients at high CV risk, including those with diabetes or established cardiovascular disease. But whether statins should be initiated for primary prevention in older adults has remained uncertain, particularly beyond age 75. 

“The STAREE trial was designed because there was equipoise, or uncertainty, around the benefits of statins as people get older,” Zoungas said. “There was clearly insufficient evidence to recommend statins for primary prevention in people aged 70 and older, and clinical guidelines have not been able to make strong recommendations [in this group of patients].”

STAREE was an investigator-initiated, double-blind, randomized, placebo-controlled trial conducted through general practices across Australia. A total of 9971 independently living adults aged 70 years or older without CV disease, diabetes, or dementia were randomized 1:1 to atorvastatin 40 mg once daily or placebo. 

The mean age of patients was 74.7 years, 51.9% were women, and 40% were aged 75 years or older. The trial had two primary endpoints. Major cardiovascular events were defined as CV death, nonfatal MI or stroke, or coronary revascularization, or persistent physical disability. 

Reduction in Major CV Events

After a median follow-up of 5.9 years, a major CV event occurred in 297 participants assigned atorvastatin compared with 412 receiving placebo, corresponding to a 30% relative reduction in risk (HR, 0.70; 95% CI, 0.61-0.82; P < .001). 

The cardiovascular benefit appeared similar in participants aged 70-74 years and those aged 75 years or older and was consistent across subgroups defined by baseline LDL cholesterol, blood pressure, body mass index, and kidney function.

The effect appeared to be driven predominantly by reductions in nonfatal events. MI occurred less frequently with atorvastatin than placebo (HR, 0.57; 95% CI, 0.43-0.75), as did coronary revascularization (HR, 0.57; 95% CI, 0.45-0.72). Stroke was numerically less frequent, but the confidence interval crossed 1 (HR, 0.87; 95% CI, 0.68-1.11). Cardiovascular mortality did not differ between groups (HR, 1.00; 95% CI, 0.72-1.37).

Mean LDL cholesterol at baseline was approximately 127 mg/dL (3.27 mmol/L). By the end of follow-up, LDL cholesterol had fallen by a mean of 48 mg/dL in the atorvastatin group compared with 16 mg/dL in the placebo group. 

No Improvement in Disability-Free Survival

The CV benefit did not translate into a statistically significant improvement in the trial’s other primary endpoint. Death, dementia, or persistent physical disability occurred in 637 atorvastatin-treated participants and 676 placebo-treated participants (HR, 0.94; 95% CI, 0.84-1.05; P = .25). 

Investigators highlighted this disconnect as a notable finding, writing that “explanations for this result might include the fact that 80% of the deaths in our trial were from noncardiovascular causes.” This may have diluted the effect of preventing cardiovascular events on overall disability-free survival.

There was no evidence that atorvastatin either increased or decreased dementia. Dementia occurred at rates of 10.6 and 10.3 events per 1000 person-years in the atorvastatin and placebo groups, respectively (HR, 1.03; 95% CI, 0.87-1.21). 

“We didn’t see any difference in incident dementia in the atorvastatin and placebo groups,” Zoungas said. “We can’t say there was any harm or any benefit from atorvastatin for that outcome.”

Safety and Tolerability

Musculoskeletal, hepatobiliary, and diabetes-related adverse events were more common with atorvastatin, but serious adverse events were uncommon and occurred in 2.7% of participants in both groups. 

Asked about using statins in older patients who may already experience muscle or joint symptoms, Zoungas noted that approximately half of STAREE participants reported a musculoskeletal issue at baseline. “I think it’s a conversation that a person needs to have with their physician, weighing up the risks and benefits and understanding whether they will be able to tolerate a statin,” she said.

Participants initially received atorvastatin 20 mg daily, increasing to 40 mg after 4 weeks if tolerated; subsequent dose reductions or re-escalation were permitted to manage side effects.

Adherence declined over time, with 80.2% of atorvastatin-treated participants still taking assigned therapy at 1 year, 66.1% at 3 years, and 55.6% at 5 years. The investigators noted that the treatment effect may therefore be conservative, particularly because open-label statin use was more common in the placebo group.

The authors cautioned that participants were predominantly White and English-speaking and were relatively healthy, independently living older adults. The findings therefore may not be generalizable to frailer older people or those with more comorbidities. 

“With the world’s population aging at an unprecedented rate, answering fundamental questions about healthy longevity has become a universal imperative,” Zoungas said. “We hope to see updated guidelines to help clinicians make use of these new findings.”

Discussant François Mach, MD, head of cardiology at Geneva University Hospital in Switzerland, described STAREE as filling an evidence gap clinicians had been waiting years to address. 

“I really think that an evidence gap has been filled,” he said, highlighting the nearly 10,000 participants, almost 6 years of follow-up, and a 30% reduction in major cardiovascular events. But he stressed an important distinction: the benefit was in preventing cardiovascular events, predominantly nonfatal events, rather than extending life. “Not cardiovascular death, not all-cause death,” he said. “STAREE demonstrates cardiovascular event prevention, not prolonged survival.”

For clinical practice, Mach said the results mean that “age alone should no longer be used as a reason to withhold statin therapy for primary prevention,” adding that lipid guidelines would need to be adapted accordingly. 

However, “STAREE does not mean that every person 70 years or older should automatically receive statin treatment,” he cautioned. Decisions should instead take account of “life expectancy, competing risk, treatment burden, and patient priorities.” He also noted that frail, multimorbid, and very old adults were underrepresented in STAREE, concluding that the remaining questions are “which older adults should we treat, for how long?” and whether preventing an event ultimately gives them “a more meaningful life.”

Zoungas has reported previous payments to an institution (Monash University) from AstraZeneca, Boehringer Ingelheim, Eli Lilly Australia, GlaxoSmithKline, Novo Nordisk, and Sanofi for participation in advisory boards, steering committees, and educational meetings not related to the current study. Mach has reported no relevant financial relationships.