Don’t Avoid Statins in Elderly, Frail Patients: Two Retrospective Studies Argue

Statins reduce the risk of adverse cardiovascular events among older adults regardless of chronic kidney disease and frailty status, according to two new retrospective studies of US veterans. Researchers say their findings should encourage physicians to not be reluctant to give the lipid-lowering drugs to these populations.

The risks and benefits of statins in elderly adults is an ongoing conversation in preventive cardiology, particularly given the potential side effects of the medications and the pill burden in patients with concomitant conditions. Concerns about nonadherence to other drugs or the perception that statin benefits take too long to accrue has led many physicians to deprescribe or avoid them entirely in older patients, especially individuals with chronic kidney disease.

Save for patients “at the very end of life,” said Ariela R. Orkaby, MD, MPH (VA Boston Healthcare System, MA), who served as a co-author on both studies, statins should not be deprescribed in the elderly.

“For the vast majority of people with chronic kidney disease, even living with frailty, they're not dying imminently,” she told TCTMD. “They may have a life expectancy of 2, 3, 4, or 5 years, and we don't want them to develop a heart attack or stroke; we don't want them to die prematurely of cardiovascular disease from a preventable condition.”

Richard Bach, MD (Washington University School of Medicine, St. Louis, MO), who wasn’t involved in either study, agreed. “The attitude that if the disease is already advanced, one won't necessarily benefit from a statin or that the risk of adverse side effects outweighs the potential benefit is wrong headed thinking, essentially,” he told TCTMD. “These patients who are at high risk have substantial benefit.”

The attitude that if the disease is already advanced, one won't necessarily benefit from a statin or that the risk of adverse side effects outweighs the potential benefit is wrong headed thinking. Richard Bach

For the first study, which was published online last week in the Journal of the American Geriatrics Society, Orkaby and colleagues included 710,313 US veterans (mean age 75.3 years; 98% male) without known CVD or prior statin use who were enrolled between 2002 and 2012. Overall, 12.1% were considered frail.

After a mean follow-up period of 8 years, there were fewer deaths and incidents of MACE per 1,000 person-years, regardless of frailty status, among those who used statins compared to those who did not.

Outcomes Per 1,000 Person-Years

Additionally, statin use was associated with lower risks of all-cause mortality (HR 0.61; 95% CI 0.60-0.61) and MACE (HR 0.86; 95% CI 0.85-0.87) with no significant interactions by frailty.

In the second paper, published online last week in JAMA Network Open, Odeya Barayev, MD, MBA (Ben Gurion University of the Negev, Be’er Sheva, Israel), Orkaby and colleagues retrospectively included 14,828 US veterans, focusing on those diagnosed with either stage 3 or 4 chronic kidney disease (CKD) and no prior atherosclerotic cardiovascular disease or statin use. Mean age at CKD diagnosis was 76.9 years, and 99% of the population were men.

Patients who had initiated statins had a lower risk of all-cause mortality on propensity score-adjusted analysis than those who had not over a mean follow-up period of 3.6 years (HR 0.91; 95% CI 0.85-0.97). Those on statins also saw a trend toward lower MACE risk (HR 0.96; 95% CI 0.91-1.02).

Orkaby said the results went beyond what she anticipated. “I wasn't expecting among frail older adults to see as strong of a protective association as we saw,” she said. “I expected it to attenuate. And we actually got the opposite, which, as I've been thinking through it, reflects the highest risk group of people—people who are frail and older.”

‘Misunderstanding’ Drives Statin Choices

Orkaby acknowledged the growing idea that statins may cause harm in some patients, although she said it is often “overstated.” This concern has led to a “misunderstanding” among physicians, wherein some have been deprescribing statins in older adults, especially those with frailty, dementia, and CKD, she explained. “A lack of data does not imply no benefit or harm. And rather, we now have emerging studies . . . that show in a real-world setting, there's no reason to believe that statins won't continue to be as effective as they were in the healthiest people enrolled in trials.”

Bach echoed the fact that multiple studies have observed increased event rates when statins are withheld, especially in those at high risk. “I am not a fan of feeling that that needs to be done,” he said. While elderly patients “need individualized therapy,” it would not be appropriate to systematically avoid statins in this population due to concerns over polypharmacy or drug-drug interactions, Bach added.

In the future, he said the guidelines should endorse more liberal use of statins in the elderly. “There has been a lack of data, and that lack of data has confounded guideline endorsement for more-aggressive lipid lowering in the elderly,” Bach said. “But I am convinced that the elderly are at high risk [and] that when we withhold effective therapies, whether it's preventive therapies or treatments, from the elderly because of our fear of adverse consequences, that may not benefit most from an absolute risk reduction standpoint.”

As such, he encouraged further study in elderly populations, challenging as that might be. “Now that we have multiple strategies for lowering lipids, more so than just statin therapy, I would love to see more widespread application of different approaches to lowering lipids aggressively in this population to see whether application to this, what I would consider a very-high-risk group, actually can improve outcomes and reduce mortality,” Bach said.

Stop using age as a reason not to do things in our work. Ariela R. Orkaby

Orkaby said she would also like to see more research aimed at better understanding the relationship between frailty and cardiovascular disease. “Are the drugs that we're giving, like statins, preventing cardiovascular disease and can they also make a difference for a healthy aging overall?” she asked. “If we can prevent heart attacks and strokes using these common meds, which are frankly cheap and safe, can they also do more good for the rest of the body?”

For now, clinicians need to “stop using age as a reason not to do things in our work and rather to look beyond that and understand what do our patients look like beyond that chronological number,” Orkaby stressed.