Statins Handed a Victory in Healthy Older People in STAREE

For the first time, a major randomized trial was able to show that primary prevention statins did have a place for healthy older adults.

Statin therapy with daily atorvastatin 40 mg was clearly favored over placebo in people 70 and older when tallying the composite of death from cardiovascular causes, nonfatal myocardial infarction (MI) or stroke, or coronary revascularization over 6 years in the large STAREE trial (10.9 vs 15.5 events per 1,000 person-years, HR 0.70, 95% CI 0.61-0.82), reported Sophia Zoungas, MBBS, PhD, of Monash University in Melbourne, Australia, at the European Society of Cardiology (ESC) meeting held this year in Munich, Germany.

Zoungas highlighted the consistency of the benefit between those ages 70-74 and older, as well as subgroups defined by LDL cholesterol level, blood pressure, body mass index, and kidney function at baseline. The effects of statin therapy were also clear despite substantial crossovers, dose titrations, and adherence issues in STAREE, a pragmatic trial mimicking real-world practice.

“The effects were especially notable and are probably conservative given the substantial percentage of participants who discontinued the trial regimen, as well as the greater use of open-label statins in the placebo group than in the atorvastatin group,” Zoungas and colleagues noted in their study manuscript, simultaneously published in the New England Journal of Medicine.

In STAREE, statin therapy was not enough to tip the scale on disability-free survival, however, as it failed to significantly lower the risk of combined death from any cause, dementia, or persistent physical disability (21.6 vs 23.0 events per 1,000 person-years, HR 0.94, 95% CI 0.84-1.05).

As for its cardiovascular benefits, statin therapy had the largest effects reducing MIs and coronary revascularization events. Deaths from cardiovascular causes were too few to support any between-group difference, the STAREE trialists noted, adding that this was also an older population prone to the competing risk of death from other causes.

“What we hope to see, now that we have provided such strong evidence, are updated treatment guidelines to help clinicians make use of this new finding,” Zoungas said in a press release.

On account of the limited data before STAREE, moderate-intensity statin therapy had been given a weak class IIb recommendation for the oldest old in this year’s American lipid guidelines.

Statins have long been a contentious topic for healthy elderly individuals with no history of cardiovascular disease, diabetes, dementia, or other life-limiting conditions. The controversy concerns their balance of efficacy and safety in this group: Whatever the potential cardioprotective benefits of statin therapy, there is also much concern over possible side effects such as muscle pain.

STAREE provided some reassurance on that front. Overall serious adverse events occurred at the same 2.7% rate between atorvastatin and placebo groups. Notably, there were small excesses in medically important adverse events related to:

• Musculoskeletal or connective tissue events: 1.1% with atorvastatin vs 0.9% with placebo
• Hepatobiliary events: 1.4% vs 0.3%
• Diabetes-related events: 1.1% vs 0.7%

“I think it’s a conversation that a person needs to have with their treating physician, weighing up the risks and benefits, and understanding whether they will be able to tolerate a statin,” Zoungas said during an ESC press conference.

STAREE had nearly 10,000 participants randomized 1:1 to atorvastatin or placebo. Individuals started on a single 20-mg dose of atorvastatin, then were uptitrated to 40 mg as tolerated.

Eligible patients were relatively healthy people 70 years or older living independently and registered as patients in primary care settings across Australia. The cohort averaged 74.7 years of age and was about evenly split between the sexes. At baseline, mean total cholesterol was 211 mg/dL, mean LDL cholesterol was 127 mg/dL, and mean HDL cholesterol was 62 mg/dL.

Following a median 5.9 years follow-up, total cholesterol fell by 53 mg/dL versus 18 mg/dL between atorvastatin and placebo groups, respectively, with LDL cholesterol dropping by 48 mg/dL versus 16 mg/dL.

In the atorvastatin group, 80.2% of patients were still taking atorvastatin at 1 year, 66.1% at 3 years, and 55.6% at 5 years. The large number of statin discontinuations in this trial was most commonly attributed to “participant unwilling” (15.6%) rather than adverse events (7.2%) or an unacceptable side-effect profile (6.1%), study authors reported.

“Combined with data from real-world studies showing 5-year adherence of only 25 to 50%, our findings highlight the point that tackling persistence with statin use remains critical to future prescribing effectiveness for primary prevention in older adults,” Zoungas and colleagues wrote.

On the other hand, statin use in the placebo group reached 3.5%, 12.1%, and 19.4% at 1, 3, and 5 years.

The STAREE investigators acknowledged that their results may have limited generalizability given that participants were predominantly white, with English as their first language, and the trial did not include frail people and those with coexisting medical conditions.

Other important statin studies are still to come, namely the U.S.-based PREVENTABLE (also testing atorvastatin 40 mg against placebo in older adults) and the recently completed STREAM from Europe (reporting on statin deprescribing in multimorbid elders).

“I think further studies may look at a higher [statin] dose or combination therapy to ascertain the safety of that as well,” Zoungas said at ESC.