乌鸦传媒

With growing evidence that lipid-lowering treatment is beneficial for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) in older people, is it time for a bigger push for statins in the elderly?

Statins are commonly used to reduce the risk of first and recurrent ASCVD events in the general population. Widely accepted as secondary prevention in the elderly, their use is more controversial in primary prevention, given feared side effects such as cognitive impairment, falls, neuropathy, and muscle damage in this population.

Statins can be especially helpful given that more people are living longer -- the number of people ages 65 and older is projected to swell to in the U.S. in the year 2060 -- and older age itself is associated with greater risks of heart disease and stroke.

In a 2020 analysis of the primary prevention cohort, people ages 70 to 100 years with elevated LDL cholesterol had the highest absolute risk of myocardial infarction and ASCVD -- and the lowest number needed to treat to prevent one event -- out of any other age group.

Although more definitive answers about statins aren't expected until completion of ongoing trials in older adults -- namely and , scheduled for 2023 and 2027, respectively -- there are existing studies suggesting that lipid-lowering treatment works just as well in the elderly as the non-elderly, said cardiac critical care specialist Marc Sabatine, MD, MPH, of Brigham and Women's Hospital and Harvard Medical School in Boston.

He emphasized the safety of lipid-lowering therapies, citing his group's showing no increase in neurological events, cancer, or hemorrhagic stroke in a study cohort of close to a quarter of a million older people -- 8.8% of whom were at least 75 years old.

While the majority of the available data on cholesterol reduction centers around statins, the benefits look equally good for ezetimibe (Zetia) and PCSK9 inhibitors, Sabatine told 乌鸦传媒.

But is it enough to push the guidelines more in favor of lipid lowering in the elderly?

These therapies are currently underutilized in older patients, noted interventional cardiologist Deepak Bhatt, MD, MPH, also of Brigham and Women's Hospital and Harvard Medical School.

The American College of Cardiology/American Heart Association noted that statin use is "reasonable" in older people for the secondary prevention of recurrent ASCVD events. When it comes to primary prevention, however, the recommendations give a weaker indication for lipid-lowering treatments, putting greater emphasis on shared decision making -- factoring in concerns about polypharmacy, life expectancy, and frailty -- in the elderly.

Similarly, their stated that statins should be first-line treatment for primary prevention of ASCVD in people with high LDL cholesterol or diabetes -- but only for those ages 40 to 75.

"The rationale for that is not clear. The data speak to the fact that the elderly benefit just as much. An additional point is the event rate in the elderly tends to be higher -- you can talk about the same relative risk reduction, but if the baseline risk is higher, then the absolute risk reduction should be even larger," Sabatine argued.

"The point I would make is that for any patient, one needs to consider what the paramount problems are. That's not to say there couldn't be elderly patients that have other issues going on, metastatic cancer for example, where the imperative to lower LDL cholesterol may not be there. For the typical patient, it doesn't make any sense to down-titrate or restrict statins or lipid-lowering therapy on the basis that they're 75 years old. There's zero logic for that," he added.

"Biological age is more important than chronological age, and in the right patients, lipid-lowering therapy can prevent heart attacks and strokes, as well as reduce the need for coronary revascularization procedures. Even if death from these causes is not a major concern to a patient, these conditions can lead to marked disability, which virtually everyone would want to avoid," Bhatt said.

For older patients who are particularly concerned about polypharmacy and side effects, he suggested ezetimibe as an option.

How exactly one might weigh the potential benefits and risks of a lipid-lowering medication in the elderly is unclear, however -- the pooled cohort equations, the standard way of determining ASCVD risk, are valid only up to age 79. Most risk calculators would have older people in a blanket category, eligible for statins by virtue of their age alone.

Without a comprehensive screening tool that stratifies ASCVD risk in old age, clinicians are left with coronary artery calcium (CAC) scoring and biomarkers such as N-terminal pro-brain natriuretic peptide, troponin, and high-sensitivity C-reactive protein for determining whether statins are needed. A CAC score of zero is said to have strong negative predictive value, indicating a person is not likely to benefit from statins for ASCVD prevention over the next 10 years, according to the guidelines.

Then there is the conundrum of how to account for frailty, cognition, and functional status. Several tools have been developed for assessing frailty, for instance, with none being clearly better than the others.

"I do think there is a need for more research in older patients, especially those who appear objectively to be frail. Likely, multidisciplinary intervention is needed in a substantial percentage of frail patients," said Bhatt.

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