Three Studies Find Statins Protect Against Cardiovascular Disease in High-Risk Groups

The 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults reported no evidence for using statins in people over 75 years of age. That paper sparked a still-ongoing debate about the benefits of initiating statin use in older people at risk for developing high cholesterol or cardiovascular disease. Out of an abundance of caution, some doctors have chosen to deprescribe statins.

Researchers at Brigham and Women’s Hospital are challenging this trend. According to geriatrician Ariela Orkaby, MD, MPH, of the Brigham’s Division of Aging, the issue is that populations at the highest risk of a cardiovascular event generally have not been included in statin trials.

To help fill this gap, Dr. Orkaby led three recent retrospective studies of statins in, respectively, older adults with chronic kidney disease, older adults with and without frailty, and adults with heart failure with preserved ejection fraction (HFpEF).

“We’re seeing a very consistent benefit for statins across these populations,” Dr. Orkaby says. “There’s more and more evidence emerging that we should reconsider deprescribing what is potentially a beneficial medication for so many.”

Study Involving People at End of Life Contributes to Misconception

Soon after the release of the 2013 guideline, a trial published in JAMA Internal Medicine found that the use of statins in people at end of life was not associated with improved outcomes.

Given that statins for primary prevention are not expected to have a benefit for about two-and-a-half years, Dr. Orkaby agrees that it is reasonable not to prescribe statins or any other preventative medication for this population. The problem, she says, is that the combination of this study and the 2013 guideline led many clinicians to stop prescribing statins altogether to older adults.

Before the end of the decade, the ACC and AHA had already reassessed their position. In their 2018 guideline, the organizations took a more neutral stance, stating, “In adults older than 75 years of age, it may be reasonable to stop statin therapy when functional decline (physical or cognitive), multimorbidity, frailty, or reduced life-expectancy limits the potential benefits of statin therapy.”

Findings from Dr. Orkaby’s trio of studies demonstrate statins have a protective effect even in people who haven’t had their first major cardiovascular event, which means there are still benefits to prescribing these medications for primary prevention of cardiovascular disease.

Reductions Seen in Mortality and Cardiovascular Events

The first of the papers, published in JAMA Network Open, was a study of 14,828 older U.S. veterans with chronic kidney disease. In a restricted analysis emulating a trial, the investigators found that starting statins was associated with a 9% reduction in mortality and a nonsignificant reduction in cardiovascular events.

“And yet when we extended out the analysis and included all the people we might see in clinical practice, we saw a significant reduction in both mortality and cardiovascular events,” Dr. Orkaby adds.

A second study, published in the Journal of the American Geriatrics Society, looked at a much larger group of older veterans without kidney disease, of whom 12.1% were frail. Among this group of 710,313 people, the researchers found that statins were associated with a 39% lower risk of mortality and a 14% lower risk of a first heart attack or stroke.

Just as people with frailty are more likely to have a heart attack or stroke, those who have cardiovascular disease are more likely to become frail. Dr. Orkaby observes that uncovering successful interventions to modify frailty can help break this cycle.

“Studies show that if you can gently and carefully bring down blood pressure in people with frailty, their frailty gets better, their walking gets better, and their risk of cardiovascular disease decreases,” she says. “Now we’re starting to ask the same questions about statins and cholesterol management. There’s very little data in this space, and we are among the first to explore this question.”

A third study, published in JACC: Advances, found that new statin use was associated with reduced all-cause mortality and major adverse cardiovascular events in veterans with HFpEF and without known cardiovascular disease.

“This is another high-risk group that has not been studied in a clinical trial and showed similar results as we saw in the other studies,” Dr. Orkaby says. “Also, in extending this paper out to look at hospitalizations, we were shocked to see a very significant reduction in heart failure-specific hospitalizations and all-class hospitalizations.”

PREVENTABLE Trial Breaking New Ground

Dr. Orkaby stresses that the conclusions of these three retrospective studies should be validated in new clinical trials. To that end, she serves as principal investigator for the Boston site of the nationwide PREVENTABLE trial, which is examining whether taking a statin could help older adults live well for longer by preventing dementia, disability, or heart disease.

Dr. Orkaby and her team recently received a major grant to extend the PREVENTABLE trial to test whether statins can prevent frailty. She hopes to have an answer to the question in five to 10 years.

For the time being, Dr. Orkaby would like to see clinicians consider more deliberately which of their older patients might benefit from a statin.

“We need to think about not just risk calculators that give us one window into the risk of cardiovascular events but also more globally about what else is going on with the patient that might further modify their risk,” she says. “Frailty, for example, is a risk factor for having a cardiovascular event, but it’s not in any of our risk assessments. So sometimes we have to take a step back, reassess, and at least start the conversation to see if it makes sense to offer the patient a statin.”

The Brigham is actively recruiting volunteers for the PREVENTABLE trial. Potential participants can learn more on this page.

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