Optimizing Lipid Lowering Drug Use Could Yield Major Clinical, Public Health Benefits

New research is shedding light on a significant gap between the number of patients for whom cholesterol-lowering drugs such as statins are guideline-recommended and the actual number of patients who take them, highlighting the clinical and public health benefits of aligning hypercholesterolemia treatment with guidelines.1

The simulation study used cross-sectional National Health and Nutrition Examination Survey (NHANES) data representing 131 million US adults and found actual lipid lowering therapy (LLT) use was significantly lower than the proportion of eligible patients for all therapies, including statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i). Fully guideline concordant care led to expected additional overall median LDL-C reductions ranging from 37.2-48.5 mg/dL, yielding a 21–27% relative reduction in the risk of major cardiovascular events.1

“High cholesterol is an important chronic health condition that silently claims far too many lives —there are millions of people walking around with this condition that don't even know they have it, and then when it is recognized it too often goes undertreated. Evidence-based action is critical to close the gap and prevent devastating cardiovascular events,” senior author Seth Martin, MD, MHS, a practicing cardiologist and professor at the Johns Hopkins University School of Medicine, said in a statement.2

Investigators note that although prior research has quantified undertreatment, these analyses leave several questions unanswered, including whether such gaps have narrowed with changes in the diagnosis and treatment of high cholesterol, as well as the magnitude of health care gains with improved LDL-C treatment.1

To project anticipated improvements in treatment and outcomes under full implementation of US and European pharmacologic treatment recommendations, investigators conducted a simulation study using cross-sectional data from NHANES from January 2013 through March 2020.1

Among the cohort, investigators estimated the number of individuals eligible to receive versus currently receiving lipid lowering therapy (LLT) after applying the following major guidelines and pathways:

• the 2018 American Heart Association (AHA)/American College of Cardiology (ACC) guideline
• The 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline
• The 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering

Additionally, they estimated the expected reduction in LDL-C and major cardiovascular events.1

A total of 4980 NHANES participants 40–75 years of age were eligible for inclusion, representing 131.1 million US noninstitutionalized adults. The median LDL-C in the weighted population was 114 mg/dL with 28% of individuals using any LLT, including statins, ezetimibe, or PCSK9i.1

Investigators included 11% of patients in the secondary prevention cohort, defined as individuals with clinical cardiovascular disease, including those who self-reported coronary heart disease, angina/angina pectoris, myocardial infarction, or stroke; all other individuals were considered part of the primary prevention cohort, which constituted 89% of the study population.1

Among 116.3 million adults eligible for primary prevention in NHANES, 23% received some LLT, primarily statins. Investigators noted many more patients were eligible for any LLT based on the 2018 US guideline (47%), the 2019 EU guideline (87%), and the 2022 US pathway (47%) than were receiving LLT.1

Among 14.8 million adults eligible for secondary prevention LLT according to all 3 recommendations, approximately 10.1 million individuals (68%) received any LLT. In addition to marked underuse of statins, investigators pointed out non-statin therapies were underutilized for secondary prevention when applying all 3 recommendations, citing 0.7 million of 14.8 million individuals (4%) received ezetimibe compared with recommendations that 4.8–11.2 million individuals should receive such treatment.1

They additionally noted no adults in the secondary prevention cohort received PCSK9i therapy for secondary prevention, as compared with their estimation that 12% of patients under the 2018 US guideline, 42% of patients under the 2022 US pathway, and 53% of patients under the 2019 EU guideline should receive this therapeutic class, representing 1.8–7.9 million US adults.1

Further analysis revealed the additional overall median LDL-C reduction expected under fully guideline concordant care was 37.2 (interquartile range [IQR], 6.7–57.6) mg/dL, 48.5 (IQR, 33.0–69.9) mg/dL, and 46.8 (IQR, 7.2–67.6) mg/dL based on the 2018 US guideline, 2019 EU guideline and the 2022 US pathway, respectively, yielding a 21–27% relative reduction in risk of major cardiovascular events.1

“These results add to a growing body of evidence that there are important shortcomings in the quality of care for common and costly chronic diseases such as high cholesterol, and that addressing those shortcomings would yield major public health benefits,” lead author G. Caleb Alexander, MD, a practicing internist and professor in the Johns Hopkins Bloomberg School of Public Health’s Department of Epidemiology, said in a statement.2

References

1. Alexander GC, Curran J, Victores A, et al. US Public Health Gains from Improved Treatment of Hypercholesterolemia: A Simulation Study of NHANES Adults Treated to Guideline-Directed Therapy. J GEN INTERN MED (2025). https://doi.org/10.1007/s11606-025-09625-0

2. Johns Hopkins Bloomberg School of Public Health. Tens of thousands of heart attacks and strokes could be avoided each year if cholesterol-lowering drugs were used according to guidelines. EurekAlert! June 30, 2025. Accessed July 10, 2025. https://www.eurekalert.org/news-releases/1089372