For the first time, a large randomized trial demonstrated that primary‑prevention statin therapy can benefit healthy older adults.
Statin therapy with daily atorvastatin 40 mg clearly outperformed placebo in participants aged 70 and older when measuring the composite endpoint of cardiovascular death, non‑fatal myocardial infarction, stroke, or coronary revascularization over six years in the STAREE study (10.9 versus 15.5 events per 1,000 person‑years; hazard ratio 0.70, 95 % CI 0.61‑0.82). Sophia Zoungas, MBBS, PhD, of Monash University in Melbourne, Australia, presented these findings at the European Society of Cardiology meeting held this year in Munich, Germany.
Zoungas emphasized that the benefit was consistent across the 70‑74 age bracket and older subgroups, as well as among participants stratified by baseline LDL cholesterol, blood pressure, body mass index, and kidney function. The therapeutic effect remained evident despite considerable crossover, dose adjustments, and adherence challenges inherent to this pragmatic trial that mirrors real‑world practice.
“The observed effects are notable and likely conservative, given the substantial proportion of participants who stopped the assigned regimen and the higher use of open‑label statins in the placebo arm compared with the atorvastatin arm,” Zoungas and colleagues wrote in their manuscript, simultaneously published in the New England Journal of Medicine.
In STAREE, statin therapy did not significantly improve disability‑free survival, as it failed to reduce the combined risk of death from any cause, dementia, or persistent physical disability (21.6 versus 23.0 events per 1,000 person‑years; HR 0.94, 95 % CI 0.84‑1.05).
Regarding cardiovascular outcomes, the greatest reductions were seen in myocardial infarction and coronary revascularization events. Cardiovascular mortality was too low to detect a between‑group difference, a limitation the investigators attributed to the advanced age of the cohort and competing risks of non‑cardiovascular death.
“We hope that this robust evidence will prompt updated treatment guidelines, enabling clinicians to apply these findings in practice,” Zoungas said in a press release.
Prior to STAREE, moderate‑intensity statin therapy had received only a weak Class IIb recommendation for the oldest old in the current American lipid guidelines, reflecting the scarcity of data.
Statins have long been debated for healthy elderly individuals without prior cardiovascular disease, diabetes, dementia, or other life‑limiting conditions. The controversy centers on weighing potential cardioprotective benefits against safety concerns, particularly muscle‑related adverse effects.
STAREE offered some reassurance on safety: overall serious adverse events occurred at an identical 2.7 % rate in both the atorvastatin and placebo groups. Slight excesses were noted in certain medically important adverse events:
- Musculoskeletal or connective‑tissue events: 1.1 % with atorvastatin versus 0.9 % with placebo
- Hepatobiliary events: 1.4 % versus 0.3 %
- Diabetes‑related events: 1.1 % versus 0.7 %
“Deciding whether to start a statin should involve a conversation between the patient and their physician, weighing risks and benefits and considering tolerance,” Zoungas remarked during an ESC press conference.
STAREE enrolled nearly 10,000 participants, randomized 1:1 to atorvastatin or placebo. Treatment began with a single 20‑mg dose of atorvastatin, which was titrated up to 40 mg as tolerated.
Eligible individuals were relatively healthy people aged 70 years or older living independently and receiving primary‑care across Australia. The cohort averaged 74.7 years of age and was roughly balanced by sex. At baseline, mean total cholesterol was 211 mg/dL, mean LDL cholesterol 127 mg/dL, and mean HDL cholesterol 62 mg/dL.
After a median follow‑up of 5.9 years, total cholesterol decreased by 53 mg/dL in the atorvastatin group compared with 18 mg/dL in the placebo group; LDL cholesterol fell by 48 mg/dL versus 16 mg/dL, respectively.
In the atorvastatin arm, 80.2 % of patients remained on therapy at one year, 66.1 % at three years, and 55.6 % at five years. The majority of discontinuations were due to participant unwillingness (15.6 %), rather than adverse events (7.2 %) or an unacceptable side‑effect profile (6.1 %).
“Combined with real‑world data showing only 25‑50 % five‑year adherence, our results underscore that maintaining persistence with statin use is essential for future effectiveness of primary prevention in older adults,” Zoungas and colleagues noted.
Conversely, statin use in the placebo group rose to 3.5 % at one year, 12.1 % at three years, and 19.4 % at five years.
The investigators acknowledge that the findings may have limited generalizability because the trial population was predominantly white, English‑speaking, and excluded frail individuals or those with significant comorbidities.
Other noteworthy statin investigations are forthcoming, including the U.S.–based PREVENTABLE trial (also testing atorvastatin 40 mg versus placebo in older adults) and the recently completed STREAM study from Europe, which examines statin deprescribing in multimorbid elders.
“Future research might explore higher statin doses or combination regimens to further assess safety,” Zoungas added at the ESC meeting.