Age Shouldn’t Be a Barrier to Statin Therapy, Meta-analysis Suggests

Age does not appear to be a limiting factor when it comes to the benefits of statin therapy, according to a new study from the Cholesterol Treatment Trialists’ (CTT) Collaboration.

In a large meta-analysis of 28 trials and 186,854 patients, statin therapy, or the use of a more intensive statin regimen versus a less intensive statin, was associated with 21% lower risk of major vascular events for every 1.0-mmol/L (38.67-mg/dL) reduction in LDL cholesterol, a finding that was observed across all age groups. Overall, the proportional reduction in events declined slightly with increasing age, but the trend was not statistically significant, investigators reported recently in the Lancet.

Colin Baigent, BMBCh (University of Oxford, England), one of the lead CTT researchers, said these new data should encourage physicians to think about statins as a means to promote disability-free aging.

“It’s not just about preventing death, although that’s obviously one thing,” Baigent told TCTMD. “Older people are often focused around avoiding disability. We know that statins prevent ischemic stroke and prevent heart attacks, and we know heart attacks can lead to heart failure in the long term. I would see offering statins to older people as one mechanism for promoting healthy aging. There’s nothing like one of those events to change somebody from a healthy elderly person into a disabled one.”

In an editorial, Bernard Cheung, MB BChir, and Karen Lam, MBBS (both from University of Hong Kong, China), state that the meta-analysis reinforces the message that statins should be considered for prevention in people at risk, including the elderly. Even if the relative risk reduction in patients 75 years and older is less than expected, their high baseline risk usually justifies initiating statins.

“Among trial participants older than 75 years, the absolute risk reduction in major vascular events was roughly 0.5% per year per 1-mmol/L decrease in LDL cholesterol,” they write. “This risk reduction would be expected to be higher in high-risk patients.” As such, the CTT meta-analysis makes the case for statin therapy in at-risk individuals regardless of their age, provided the benefits outweigh the harms and the patient accepts long-term treatment, say Cheung and Lam.    

Potential For Real Gains in Older Patients

The meta-analysis, published January 31, 2019, and conducted in collaboration with Australia’s University of Sydney NHMRC Clinical Trials Center, focused on the influence of advancing age on major vascular endpoints in 28 trials. In 23 of those studies, a statin was compared with placebo or usual care, while an intensive statin regimen was compared against a standard statin regimen in five other trials. Twenty percent of participants were 66-70 years, 15% were 71-75 years, and 8% were older than 75 years.

Among the most-elderly patients, those older than 75 years, use of a statin or the more intensive regimen was associated with a significant 13% reduction in risk of major vascular events for every 1.0-mmol/L reduction in LDL cholesterol. When investigators excluded trials that included patients with heart failure and dialysis, each 1-mmol/L reduction in LDL cholesterol was associated with an 18% reduction in major vascular events among this elderly population.  

Overall, major coronary events were reduced by 24%, although there was a statistically significant trend toward lesser benefit with increasing age (P = 0.009). Still, even among those older than 75 years, statin therapy was associated with a significant 18% reduction in major coronary events. Stroke and coronary revascularization were also reduced by 16% and 25%, respectively, with each 1-mmol/L reduction in LDL cholesterol, and this benefit did not differ significantly by age.

Investigators also stratified patients into primary and secondary prevention. For those with vascular disease, statin therapy reduced the risk of major vascular events by 20% and the benefit was consistent across all age groups. Among those without vascular disease, statin therapy reduced major vascular events by 25%, though there was a statistically significant trend toward smaller proportional reductions in risk with advancing age (P = 0.05). For example, statins were associated with a significant 22% reduction in vascular events among primary prevention patients younger than 55 years, but there was no reduction observed in those 70 years and older.      

If we aren’t taking advantage of what we know about the efficacy and safety of statins in the elderly, then we’re missing the point. We should be doing what we can with the tools we already have available to us. Colin Baigent

To TCTMD, Baigent said that an elderly patient with vascular disease has a higher absolute risk of major vascular events than a younger patient with similar risk factors. Despite this, not all older patients necessarily receive a statin.  

“They might get treated, but they might not receive an intensive dose of statin,” he said. “We know that more is better when it comes to statin therapy, so it’s trying to get the message out there that the reduction in risk is similar as it is in younger patients. . . . There is a real potential for gains in older people who have vascular disease.”

For primary prevention, Baigent said there weren’t enough events in the older subgroups to get definitive answers. While it would be helpful to have more evidence of the benefits of statins in the very elderly without any history of vascular disease, the overall evidence available is that the “treatment effects are definite and evident across all ages,” he observed. Moreover, given that statins are relatively safe drugs with rare side effects, it’s reasonable to assume they’d be effective in those older than 75 years. There is an ongoing clinical trial investigating the benefits and risks of statins in subjects 70 years and older in Australia, but results are a number of years away.

For Baigent, his personal opinion is to offer statins to elderly primary-prevention patients for the promotion of healthy living. Epidemiologists, trialists, and physicians are often focused on middle-aged patients given the desire to reduce the burden of cardiovascular disease but overlook older individuals, he said.

“The demographic of people at risk for cardiovascular disease is overwhelmingly elderly,” he continued. “If we aren’t taking advantage of what we know about the efficacy and safety of statins in the elderly, then we’re missing the point. We should be doing what we can with the tools we already have available to us.” 

Statins Underutilized in the Elderly

Seth Martin, MD (Johns Hopkins University, Baltimore, MD), who was not involved in the study, said that in secondary prevention, it’s clear that statins show a consistent benefit with LDL lowering across the age groups. Nonetheless, it’s humbling to see there remain certain patient populations, such as the very elderly without vascular disease, where there are limited data despite decades of statin research, he commented.

US guidelines for the management of cholesterol exclude patients 75 years and older, mainly because of the sparse data in these older patients. Martin said that when treating an older patient without preexisting cardiovascular disease, he will have a frank discussion concerning their clinical risk, aware that the absolute risk of cardiovascular events is higher in the elderly. In such instances, shared decision-making is critical.

“Often these patients will be on a number of medications already, either blood-pressure medications, anticoagulants for atrial fibrillation, or other noncardiovascular agents, so part of the conversation is about where they currently are, such as their preferences for starting an additional medication if indicated,” said Martin. “But I’m counseling them to take this seriously because statins are, all in all, underutilized in the elderly population, and this is something that should be high up on the list of their health priorities, especially given their older age.”

While cardiovascular risk reduction is often a high priority for many elderly patients, other comorbidities, such as cancer or advanced heart failure, could impact their decision to start an additional medication.

In some patients, Martin might request a coronary artery calcium (CAC) test to potentially rule out the need for statin therapy, as per the new 2018 cholesterol guidelines. A CAC score of zero in a 70-year-old patient would be “remarkable,” although it’s more common than you’d think, said Martin. The discussion with the patient would also include a look at their diet and lifestyle to determine if changes could be made to lower their cardiovascular risk.