Researchers Call for Better Risk Stratification Methods in Older Individuals With Hypercholesterolemia

The National Lipid Association and American Geriatrics Society have released a Joint Scientific Statement regarding the management of hypercholesterolemia in adults older than 75 years without a history of atherosclerotic cardiovascular disease (ASCVD), reviewing current evidence and offering recommendations for clinical decision-making in this population.¹

“Older persons have many competing medical and social needs, so treating high cholesterol in those without cardiovascular disease may not always be straightforward for clinicians and patients,” said Vera Bittner, MD, MSPH, MNLA, co-chair of the scientific statement, in a news release. “We hope to help provide as much clarity as possible.”²

Challenges of Treating Hypercholesterolemia in Older Adults

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High cholesterol is a known risk factor for heart disease and is incredibly common. In 2018, 25.2 million Medicare beneficiaries were prescribed LDL-C–lowering therapies.³ The risk of developing ASCVD increases with age, and elevated low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) are predictive of incident atherosclerotic cardiovascular events in individuals aged 75 and older; however, risk prediction in this population is challenging, as most current risk calculators lack specificity for this age group and do not adjust for comorbidities, functional status, frailty, and cognition, which all significantly impact prognosis.¹

In addition to limited risk prediction ability, data on the use of statins to lower LDL-C in older adults without ASCVD are also limited, and the authors of the Joint Scientific Statement noted that most primary prevention trials have included primarily younger participants. The body of available data suggests that statin therapy in older adults may reduce atherosclerotic cardiovascular events, and benefits may outweigh the risks, such as statin-associated muscle symptoms and incidence of type 2 diabetes.¹

The authors also noted that the US population is continuing to age, resulting in a growing population of individuals over 75 years of age living without diagnosed cardiovascular disease. However, deciding whether and how to treat high cholesterol in this patient population can be challenging due to lack of clinical trial data, comorbidities, polypharmacy, and competing goals of care.¹

Joint Scientific Statement

In the Joint Scientific Statement, investigators asked 8 questions regarding the association between LDL-C and ASCVD, how ASCVD risk should be assessed, the effects of statin therapy, and considerations for clinicians regarding statin use.¹

When weighing the potential concerns of statin therapy against the benefits, the authors noted that older adults are more susceptible to iatrogenic risks from medications due to age-related changes in metabolism, body composition, mitochondrial energetics, and cognition. However, meta-analyses and observational data have not found an increased risk of statin-associated muscle symptoms in those older than 75 years compared to younger individuals. Additionally, although statin therapy does lead to a small increase in the risk of new-onset type 2 diabetes, the risk is outweighed by reductions in major cardiovascular events, according to the authors.¹

Comorbidities and life expectancy can vary widely, and individual considerations must be considered when deciding whether to treat a patient with statin therapy. For instance, frailty ranges in prevalence from 7% in community-dwelling older adults to over 50% of patients in long-term care facilities. The authors noted that numerous tools are available to help assess geriatric conditions, and decision aids can be useful for assessing patient preferences.¹

Among adults older than 75 years without established ASCVD, specific strategies can be used to initiate, monitor, and intensify statin therapy when indicated. Shared decision-making should be employed to seek the patient’s participation, encourage them to be active participants in exploring treatment options, and reach a decision together. Safety and efficacy monitoring among older adults follows conventional standards of care.¹

Deprescribing is also an important consideration and is an essential component of high-quality care for older adults with multiple comorbidities who are susceptible to medication-related harms. The general principles of deprescribing include viewing it as a routine part of care to improve patient well-being and shared decision-making.¹

Future Directions

Several ongoing clinical trials will help improve the body of knowledge for statin benefit in older adults without a history of ASCVD and will provide further guidance for clinicians. These include the STAREE trial with approximately 10,000 participants and the PREVENTABLE trial, which is currently enrolling 20,000 community-dwelling US adults.¹

The STAREE trial, conducted in Australia, has enrolled adults aged 70 years and older to evaluate the effects of atorvastatin 40 mg daily compared to placebo in patients without ASCVD, diabetes, or dementia. Over an anticipated 6 years of follow-up, researchers intend to assess disability-free survival, major cardiovascular events, dementia, stroke, heart failure, cancer, hospitalization or institutionalization, and quality of life. The study is expected to be complete in December 2025.⁴

Meanwhile, the PREVENTABLE trial is currently enrolling 20,000 US adults aged at least 75 years without ASCVD, dementia, or disability. Like STAREE, this trial will evaluate the effects of atorvastatin 40 mg daily versus placebo for 5 years and for similar patient-oriented outcomes. Secondary outcomes include physical performance, frailty, heart failure, and quality of life. PREVENTABLE is expected to be complete in December 2026.⁵

Conclusion

The updated Joint Scientific Statement underscores the complexities inherent in managing hypercholesterolemia in older adults. Although the established link between elevated LDL-C and ASCVD remains pertinent, the statement emphasizes the need for nuanced clinical judgment beyond traditional risk calculators.

Pharmacists, as integral members of the health care team, are uniquely positioned to synthesize patient-specific factors such as comorbidities, polypharmacy, functional status, and individual preferences alongside the available evidence. By engaging in thorough medication reviews and patient counseling, pharmacists can play a crucial role in optimizing statin therapy, mitigating potential iatrogenic risks, and ultimately contributing to personalized and effective cardiovascular disease prevention strategies in this growing population.

REFERENCES

1. Bittner V, Linnebur SA, Dixon DL, et al. Managing hypercholesterolemia in adults older than 75 years without a history of atherosclerotic cardiovascular disease: an Expert Clinical Consensus from the National Lipid Association and the American Geriatrics Society. J Clin Lipidol. 2025;19(2):215-237. doi:10.1016/j.jacl.2024.09.005

2. National Lipid Association and American Geriatrics Society Release Joint Scientific Statement on Managing Hypercholesterolemia in Older Adults Without History of Atherosclerotic Cardiovascular Disease. News release. American Geriatrics Society. April 10, 2025. Accessed April 30, 2025. https://www.americangeriatrics.org/media-center/news/national-lipid-association-and-american-geriatrics-society-release-joint#:~:text=April%2010%2C%202025%20%E2%80%94%20The%20National,making%20in%20this%20unique%20population

3. Linnebur SA, Bittner V. Editorial for “managing hypercholesterolemia in adults older than 75 years without a history of atherosclerotic cardiovascular disease: an Expert Clinical Consensus from the National Lipid Association and American Geriatrics Society.” J Am Ger Soc. 2025. doi:10.1111/jgs.19452

4. STAREE. Monash University. Accessed April 30, 2025. https://www.monash.edu/medicine/staree/home

5. PREVENTABLE. Accessed April 30, 2025. https://www.preventabletrial.org/home.cfm