Study offers guidance on stopping statins in older adults without cardiovascular disease

Key takeaways:

• In older adults with multimorbidity but no cardiovascular disease, stopping statins was noninferior to continuing them at 2 years.
• Risk increased with longer follow-up.
• The results point to the need for individualized decisions.

CHICAGO — For older adults with several chronic conditions but no known cardiovascular disease, discontinuing statin therapy may be a reasonable choice, according to findings from the STREAM trial.

In nearly 1,900 adults age 70 years and older who were randomly assigned either to stop or keep taking a statin, stopping the drug was noninferior to continued treatment for time to major cardiovascular events or death at 2 years, said Nicolas Rodondi, MD, director of the Institute of Primary Health Care at the University of Bern in Switzerland. He presented the results during a late-breaking science session at the American Heart Association Scientific Sessions, and the study was published at the same time in The New England Journal of Medicine.

With follow-up extended to 4 years, however, the researchers saw a higher cardiovascular risk among a small number of older adults in the discontinuation group, Rodondi said.

The study found no meaningful differences between the two groups in quality of life, pain, falls, sarcopenia risk or medication adherence.

“This is an important piece of an evolving puzzle about statins for primary prevention ... in older adults,” Karen Alexander, MD, professor of medicine at Duke University, said during a press conference discussion of the trial. “Deprescribing is something our patients are very interested in. We often get asked: ‘Which drugs can I stop?’”

STREAM results

The open-label, randomized STREAM trial enrolled older adults with a mean age of 77.5 years, 46.9% of whom were women, who had at least two chronic conditions and were taking a statin for primary prevention of cardiovascular disease. One-third had diabetes, 90% had hypertension, 10% were current smokers, about one-third had a family history of cardiovascular disease and roughly 29% had cancer. Half of the participants were recruited by general practitioners.

The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal ischemic stroke or death from any cause.

At 2 years, mean event-free survival was 96.5 weeks in the statin discontinuation group and 98.5 weeks in the continuation group, a difference of 2 weeks between groups (95% CI, –3.7 to –0.3; P < .001 for noninferiority), the researchers reported.

“For every 40 individuals who discontinued statins, there was one additional cardiovascular event over 2 years,” Rodondi said.

At a maximum follow-up of 4 years (median, 103 weeks), the discontinuation group had higher rates of MI (1.6% vs. 0.6%), ischemic stroke (2.2% vs. 0.8%) and all-cause death (9.8% vs. 8%).

Serious adverse events were similar in both groups.

Based on STREAM, statin discontinuation in this population appears “generally safe,” but the decision should be centered on the individual patient, Rodondi said.

“If you have a very sick, old patient with a lot of other severe chronic conditions [and] likely not a long life expectancy, the 2-week difference [in event-free survival] might not be worth continuing to take a statin if they have other issues. ... For an older adult [who is] very healthy, with some other chronic conditions ... it may be wise to discuss [a plan] to continue a statin.”

“Although international guidelines generally support statin therapy in older adults with chronic conditions, some international guidelines recommend considering statin discontinuation in these persons or in selected circumstances, such as limited life expectancy,” the researchers wrote in NEJM. “Recent surveys also found that both older adults and general practitioners ranked lipid-modifying agents among the top candidates for deprescribing; our findings provide information for shared decision-making about cautious statin discontinuation when statins are used for primary prevention only. Although deprescribing inappropriate drugs in older adults appears to be safe, the results of our trial suggest that additional randomized trials of discontinuation are needed for specific drugs; the use of other cardiovascular preventive medications over the period of follow-up should also be assessed, because these cointerventions can bias results.”

‘Acceptable risk’

Commenting on the findings, Alexander said STREAM should not be read as a signal to stop primary prevention medicines broadly. “This was a noninferiority trial, and the noninferiority margin was set at 5.2 fewer weeks free of cardiovascular events at 2 years. And they did not [exceed] that noninferiority margin, which was great.

“That could be interpreted from that definition as safe. However, there were 2 to 2.4 fewer weeks free from the cardiovascular composite events with statin discontinuation. So, it was not as though there were no cardiovascular events accumulating, and you saw the rate at 4 years was higher in those who discontinued statins for cardiovascular events.”

Press conference moderator Amit Khera, MD, MSc, clinical chief of cardiology and director of preventive cardiology and epidemiology at the Peter O’Donnell Jr. School of Public Health at UT Southwestern Medical Center, said the investigators used the word “safe” to describe the results. “I might say ‘acceptable risk’ ... there was at least acceptable risk in deprescribing in the right population.”

Alexander added that another important point is that stopping statins did not make participants feel better.

In STREAM, “these were people who were tolerating statins; they were selected to be randomized to stop. And those who stopped them didn’t feel any better. ... There are lots of reasons why people who are older don’t feel good, but it would seem as though stopping statins is not going to be the answer. ... Where I would head next, is I would say, ‘let’s talk about your likely benefit from statins, because we know that if you’ve got a lot of benefits, stopping them could contribute to more events in the next 2 years,” Alexander said.

Alexander said decisions about stopping statins in this population should be made through shared decision-making.

“To do shared decision-making, we have to have evidence, and they provided us ... some really important evidence in the STREAM trial about what to expect when one deprescribes,” Khera said.

Sources/Disclosures

Source:

Rodondi N, et al. LBS.03. Late-breaking science: Hot topics in CVD prevention. Presented at: American Heart Association Scientific Sessions.

Disclosures: Rodondi reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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