A large observational study has shown no benefit from statin therapy for primary prevention of atherosclerotic cardiovascular disease (CVD) or all-cause mortality in nondiabetic adults aged 75 and older. Atherosclerotic CVD was a composite of coronary heart disease (fatal and nonfatal angina, fatal and nonfatal myocardial infarction, or cardiac revascularization), and stroke (fatal and nonfatal ischemic stroke).

However, for those with type 2 diabetes, statins did reduce the risk for atherosclerotic CVD and death, but only up to age 85, the researchers report.

"Statin prescription in older populations needs a more refined adjustment to those persons who could benefit from it, like persons with type 2 diabetes, as evidenced in our results," lead investigator Rafel Ramos, MD, PhD, Jordi Gol Institute for Research in Primary Care, University of Girona, Spain, told the heart.org | Medscape Cardiology.

"This implies the need to individualize the decision-making process about statin treatment in old and very old populations," said Ramos. "We think that we need specific risk prediction tools for these older people, the result of which should be shared with patients in a comprehensible way so they can participate in the decision of taking statins or not.

"We also consider that the current risk threshold for statin indication (10% risk of atherosclerotic CVD at 10 years) might need reevaluation in this population," he added.

The study was published online September 5 in the BMJ.

Statin prescriptions to elderly patients have increased in recent decades, but evidence to support statin treatment in primary prevention for people aged 75 years or older is lacking.

Using data from the Catalan primary care system database, Ramos and colleagues identified 46,864 people aged 75 and older (mean age, 77; 63% women) with no history of CVD between 2006 and 2015. A total of 7502 individuals (16.0%) were taking a statin, and 7880 (16.8%) had type 2 diabetes. The median follow-up was 5.6 years.

In those without diabetes, statin treatment was not associated with a reduction in CVD or all-cause mortality in both old (75 to 84 years) and very old (85 and older) age groups, even though the risk for CVD in both groups was higher than the risk thresholds proposed for statin use in guidelines, the researchers report.

In individuals with diabetes, however, statin therapy was significantly associated with reductions in CVD (24%) and all-cause mortality (16%) in those aged 75 to 84 years. But this protective effect was substantially reduced after age 85 and disappeared in nonagenarians, they note.

Table. Outcomes Risk With and Without Diabetes

Endpoint Without Diabetes With Diabetes Age 75 - 84 CVD 0.94 (0.86 to 1.04) 0.76 (0.65 to 0.89) All-cause mortality 0.98 (0.91 to 1.05) 0.84 (0.75 to 0.94) Age 85+ CVD 1.00 (0.80 to 1.24) 0.82 (0.53 to 1.26) All-cause mortality 1.00 (0.90 to 1.11) 1.05 (0.86 to 1.28)

"These results do not support the widespread use of statins in old and very old populations, but they do support statin treatment in selected people such as those aged 75-84 with type 2 diabetes," write the authors.

The key strength of the study, they say, was the high-quality, internally validated database of electronic medical records that provided a large sample size and reflected real-life clinical conditions. However, the study was observational, so no firm conclusions can be drawn about cause and effect, and residual confounding cannot be ruled out, they note.

In a linked editorial, Aidan Ryan of University Hospital Southampton, United Kingdom, and colleagues say these observational findings are exploratory and should be tested further in randomized trials "to rule out any confounding and to study the effect of statins on CVD death, which were not recorded in the database used for this study."

They point out that an ongoing clinical trial in Australia, the Statins for Reducing Events in the Elderly (STAREE) trial, is comparing atorvastatin 40 mg with placebo for primary prevention in adults older than 70 years.

"The investigators hope to recruit 18,000 participants and aim to report findings in 2022," they write. "The challenge for investigators will be whether they can run the trial long enough to evaluate slowly progressive conditions such as cognitive impairment."

In the meantime, they say "patient preference remains the guiding principle while we wait for better evidence."

Observational data have shown that researchers and patients may have different priorities in the aims of treatment, the editorialists add. Patients older than 65 prioritized reductions in myocardial infarction and stroke over death, in contrast to both researchers and younger patients.

"Therefore, if in the process of shared decision making, older patients express a preference for extending longevity, then current evidence supporting statins for primary prevention remains limited," they conclude. "A patient preference for reduction in myocardial infarction or stroke, however, might help to tilt the balance in favor of statin prescription but the absolute risk reduction, number needed to treat to prevent a CVD event in older patients remains uncertain."

The study had no commercial funding. The authors and editorial writers have disclosed no relevant financial relationships.

BMJ. Published online September 5, 2018. Full text, Editorial