An Observational Study to Evaluate Treatment Patterns in High, Very High and Extreme Cardiovascular Risk Patients With Hypercholesterolemia, Including Familial Hypercholesterolemia

TRAP-HC is a multicenter, prospective, longitudinal observational study designed to evaluate real-world treatment patterns in adult patients with hypercholesterolemia, including familial hypercholesterolemia (FH), who are at high, very high, or extreme cardiovascular risk. The study aims to generate real-world evidence on lipid control and optimization of lipid-lowering therapies (LLTs) in order to improve cardiovascular risk reduction strategies in high-risk populations.

Cardiovascular disease remains the leading cause of mortality worldwide, and elevated low-density lipoprotein cholesterol (LDL-C) is a major causal determinant of atherosclerotic cardiovascular disease (ASCVD). Current European guidelines recommend a ≥50% reduction in LDL-C levels and the achievement of stringent LDL-C targets in patients at high, very high, and extreme cardiovascular risk. Nevertheless, real-world evidence indicates that a substantial proportion of patients fail to achieve recommended therapeutic goals despite the availability of effective lipid-lowering therapies. European observational studies have shown that approximately 80% of high- and very high-risk patients do not achieve LDL-C targets, with monotherapy still widely used in clinical practice. These findings highlight the need for improved therapeutic strategies and optimization of lipid management in routine care.

The primary objective of the study is to evaluate the evolution of lipid-lowering treatment strategies over a 12-month follow-up period, with particular focus on therapeutic modifications implemented in response to LDL-C levels, the proportion of patients achieving recommended LDL-C targets, and the factors associated with successful target attainment, including baseline cholesterol levels, treatment type, demographic characteristics, comorbidities, and genetic predisposition. The study will also assess patient adherence to prescribed therapies, including treatment persistence, prescription refill patterns, and therapy discontinuation.

Approximately 2,500 adult patients will be enrolled across up to 15 Italian centers affiliated with the LIPIGEN network, all specialized in the management of dyslipidemias. Approximately 85% of the study population is expected to consist of non-FH patients whose cardiovascular risk will be classified according to current clinical guidelines, considering factors such as age, sex, LDL-C levels, blood pressure, smoking status, and other cardiovascular risk markers.

The study is observational and non-interventional in nature; therefore, no treatment assignment or protocol-driven therapeutic modification will be performed by investigators. All patients will continue to receive standard clinical care according to routine medical practice. Patient recruitment is expected to occur over a 6-month enrollment period, followed by a 12-month observational follow-up for each participant. Data routinely collected during clinical practice will be recorded approximately every 6 months when available.

At baseline, the study will collect demographic data, anthropometric measurements, cardiovascular history, major adverse cardiovascular events (MACE), diagnosis of familial hypercholesterolemia, relevant comorbidities, lipid profile parameters, liver and renal function tests, creatine kinase levels, and current or previous lipid-lowering therapies. Physical examination findings and vital signs will also be recorded.

During follow-up visits, lipid profile changes, treatment modifications, adherence to therapy, adverse events (AEs), and serious adverse events (SAEs) will be documented according to routine clinical practice. All data will be entered into an electronic Case Report Form (eCRF), and quality control procedures will be implemented to ensure data accuracy and completeness.

Eligible participants include adult patients (≥18 years) diagnosed with hypercholesterolemia, either clinical or genetic familial hypercholesterolemia, as well as non-FH patients classified as being at high, very high, or extreme cardiovascular risk. Patients with significant secondary dyslipidemias, including hypertriglyceridemia, or those undergoing treatment modifications for conditions unrelated to hypercholesterolemia, will not be enrolled.

The primary statistical analysis will evaluate changes in LDL-C levels over time using repeated-measures ANOVA, adjusting for covariates such as age, sex, and baseline LDL-C values. Secondary analyses will evaluate adherence to lipid-lowering therapies using the Proportion of Days Covered (PDC) methodology and mixed-effects logistic regression models, while treatment modifications will be analyzed using logistic regression methods. Exploratory subgroup analyses according to age, sex, cardiovascular risk category, and FH status will also be performed.

The planned sample size of approximately 2,500 patients is expected to provide 80% statistical power to detect a mean LDL-C reduction of 10 mg/dL over 1 year, assuming a standard deviation of 25 mg/dL and a significance level of 5%.

The study will be conducted in compliance with applicable Italian and European regulations for observational research, including GDPR requirements and the principles of ICH GCP adapted for non-interventional studies. As a non-profit observational study, the research will be conducted exclusively for scientific and public health purposes and not for promotional or commercial use.