Primary Prevention Benefits of Lowering LDL Also Apply to the Elderly

The primary prevention benefits of lowering LDL cholesterol were similar between statin users under and over the age of 70 years, a Danish nationwide cohort study found.

Each 1 mmol/L reduction in LDL cholesterol achieved was associated with a lower risk of major vascular events in older (HR 0.77, 95% CI 0.71-0.83) and younger individuals alike (HR 0.76, 95% CI 0.71-0.80) after 2.5 years of follow-up, starting 1 year after the start of lipid-lowering therapy with statins alone or with other agents.

Events prevented regardless of the age cutoff were a composite of acute coronary syndrome, nonhemorrhagic stroke, and coronary revascularization — all similarly reduced in a separate analysis using a cutoff of 75 years, reported researchers led by Niklas Andersson, MD, of Statens Serum Institut in Copenhagen, Denmark.

“Of note, any potential clinical benefit should be balanced against the potential of harm, and this study did not assess the safety of lipid-lowering treatment according to age,” the study authors cautioned in the Journal of the American College of Cardiology.

Given that the study’s observational study design left room for residual confounding, more robust evidence is anticipated from the ongoing large STAREE trial — scheduled for completion in 2025 — that includes patients over 70 without atherosclerotic cardiovascular disease (CVD) randomized to atorvastatin (Lipitor) or placebo.

Widely accepted as secondary prevention in the elderly, lipid lowering is more controversial in primary prevention due to concerns about cognitive impairment and muscle damage in this population — and limited evidence.

“Evidence from clinical trials of treatments lowering LDL cholesterol has shown that the relative risk of major vascular events is reduced by about one-fifth per each 1 mmol/L lowering of LDL cholesterol. For older individuals, however, data to support the benefit of LDL cholesterol-lowering treatment for cardiovascular risk reduction are sparse because elderly people are generally underrepresented in the individual trials,” Andersson and colleagues noted.

As a result, U.S. and European guidelines only weakly endorse statins for primary prevention in older people. The U.S. Preventive Services Task Force deems the evidence insufficient to recommend initiating statin use in this setting past age 76.

The findings from the present Danish study are in contrast to a 2019 Cholesterol Treatment Trialists’ Collaboration meta-analysis reporting an attenuation of benefit of statin therapy for primary prevention of CVD in people older than 75 years.

“Balancing risk and benefit is particularly crucial in primary prevention, and more so in the older population, where conditions such as statin-induced myalgias can have a disproportionate impact,” commented Safi Khan, MD, MS, of Houston Methodist DeBakey Heart and Vascular Center, in an accompanying editorial.

“Ultimately, physicians must have comprehensive discussions with patients about the potential harms and benefits of LDL-[cholesterol] reduction therapy to guide informed personalized treatment choices,” he wrote.

For the study, Andersson’s group relied on Danish registries to identify people who initiated lipid-lowering medications from 2008 to 2017 with no history of atherosclerotic CVD. Eligible individuals were required to have a pair of LDL cholesterol measurements around the time they started therapy, usually statins alone or in combination with other lipid-lowering drugs.

The final cohort included 49,155 people ages 50-69 (53% women, mean age 60.2 years) and 16,035 older peers over 70 (57.5% women, mean age 75.5 years).

In both groups, nearly 80% initiated lipid-lowering treatment of moderate intensity. The overall cohort reached a median LDL cholesterol reduction of 1.7 mmol/L, corresponding to median percentage LDL cholesterol reductions of approximately 45% in both age groups.

Lipid lowering conferred no reduction in mortality for either the young or the old.

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