The LDL-C Gap in Statin-Treated Patients: A Population-Level Problem with Economic Consequences

Despite guideline-based statin therapy, a substantial proportion of U.S. adults with or at risk for atherosclerotic cardiovascular disease (ASCVD) remain above their low-density lipoprotein cholesterol (LDL-C) targets. A large retrospective cohort analysis by Ortiz et al., published in the Journal of Medical Economics, highlights the clinical and economic implications of persistent LDL-C elevation across primary and secondary prevention populations.

Using Merative MarketScan administrative claims linked with laboratory data from 2017 to 2021, the study assessed LDL-C goal attainment, cardiovascular event rates, and healthcare resource use across more than 260,000 statin-treated patients. These findings were extrapolated to national estimates to characterize unmet needs in primary prevention, secondary prevention (stratified by risk), and untreated hypercholesterolemia cohorts.

Patients were followed for two years and stratified by LDL-C targets defined by prevention category:

• <100 mg/dL for primary prevention,
• <70 mg/dL for not very high-risk secondary prevention,
• <55 mg/dL for very high-risk secondary prevention.

Findings on LDL-C Target Failure

Among nearly 125,000 statin-treated patients who failed to meet LDL-C goals, the modeled national impact was considerable:

• 43 million patients in primary prevention with 40% above goal
• 9.8 million in very high-risk secondary prevention with 78% above goal
• 9.1 million in not very high-risk secondary prevention with 60% above goal
• An additional 9.5 million untreated patients with 84% above goal

Failure to meet LDL-C goals was clearly linked to worse outcomes. Among statin-treated patients, 28% of those above goal experienced a cardiovascular event compared to 14% among those at goal. Myocardial infarction rates were nearly three times higher in the above-goal group (14% vs. 5%).

Similarly, event rates for stroke, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) were also elevated in patients who did not achieve their LDL-C targets.

Correlation Between LDL-C and Healthcare Costs

The analysis found a graded increase in healthcare utilization across risk strata:

• Emergency department visits: 63% in secondary prevention vs. 43% in primary prevention
• Inpatient stays: 49% vs. 20%
• Long-term care use: 11% vs. 3%

Annualized healthcare costs were also markedly higher:

• $6,300 per patient in primary prevention
• $14,100 in secondary prevention overall (+124%)
• Up to $17,900 in very high-risk secondary prevention (+83% vs. not very high-risk group)

Medical costs were particularly pronounced—158% higher in secondary vs. primary prevention—while pharmacy costs were approximately 60% higher.

Gaps in Treatment Intensification

Despite widespread failure to reach LDL-C goals, uptake of adjunctive therapies remained low. In a comparable registry population, only 5.9% of patients used ezetimibe, and just 1.7% used PCSK9 inhibitors. Barriers to broader adoption include tolerability concerns, high cost, limited familiarity with non-statin options, and persistent treatment inertia.

Emerging therapies such as bempedoic acid and the CETP inhibitor obicetrapib show potential to further lower LDL-C but are not yet widely adopted. Modeling studies suggest that combinations of statins with newer agents could substantially close the LDL-C gap, but observational data suggest that these targets are not yet being met in routine care.

Study Limitations and Clinical Implications

The study is limited by its retrospective design and reliance on claims data, which may not fully capture reasons for treatment decisions or patient adherence. Clinical outcomes were associated with LDL-C levels, but causality cannot be established.

Nonetheless, the linkage between LDL-C target failure, increased cardiovascular events, and elevated healthcare costs is compelling. A significant proportion of statin-treated patients in both primary and secondary prevention remain above LDL-C targets, with clear implications for cardiovascular risk and healthcare spending.

Closing the LDL-C gap may require greater uptake of adjunctive therapies, system-level interventions to address treatment inertia, and consideration of novel agents for high-risk patients. For clinicians, achieving LDL-C targets remains a central lever in reducing cardiovascular risk and mitigating the cumulative burden of care in high-risk populations.

Reference

Ortiz N, Shehata J, Smart J, et al. Assessment of unmet clinical needs and healthcare resource use among statin-treated patients with or at risk of developing atherosclerotic cardiovascular disease. J Med Econ. 2025;28(1):1616–1625. doi:10.1080/13696998.2025.2558314