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

An Observational Longitudinal Multicenter Prospective Study to Evaluate Treatment Patterns in High, Very High and Extreme Cardiovascular Risk Patients With Hypercholesterolemia, Including Familial Hypercholesterolemia, Over a 1-Year Follow- Up

TRAP-HC is a multicenter, observational, longitudinal, prospective study designed to evaluate real-world treatment patterns and lipid-lowering therapy (LLT) management in patients with hypercholesterolemia, including familial hypercholesterolemia (FH), who are at high, very high, or extreme cardiovascular risk. Approximately 2,500 adult patients will be enrolled across up to 15 Italian LIPIGEN network centers and followed for 12 months as part of routine clinical practice.

The study aims to assess LDL-C goal attainment according to current European guidelines, evaluate changes in lipid profiles over time, and investigate treatment adherence, persistence, and therapeutic modifications in response to clinical needs. Data collected during routine visits will include lipid parameters, cardiovascular history, concomitant therapies, safety outcomes, and patient-reported adherence measures.

By providing real-world evidence on the management of hypercholesterolemia in high-risk populations, the study seeks to identify current gaps between guideline recommendations and clinical practice and to support optimization of cardiovascular risk reduction strategies.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypercholesterolaemia; Familial Hypercholesterolaemia; CVD Risk

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 2500

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (≥18 years) with hypercholesterolemia, including those diagnosed with familial hypercholesterolemia (clinical or genetic FH), or patients at high, very high or extreme CVD risk with a baseline visit during a six-month enrollment window.

Description

Inclusion Criteria:

• Age ≥ 18 years
• Diagnosis of hypercholesterolemia (including clinical or genetic FH) OR high/very high/extreme CV risk
• Baseline visit within enrollment window (six months)

Exclusion Criteria:

• Significant secondary dyslipidemia (e.g. hypertriglyceridemia)
• Treatment changes due to non-hypercholesterolemia conditions

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with hypercholesterolemia or patients at high, very high or extreme CVD risk; Adult patients (≥18 years) with hypercholesterolemia, including those diagnosed with familial hypercholesterolemia (clinical or genetic FH), or patients at high, very high or extreme CVD risk with a baseline visit during a six-month enrollment window.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LDL-C Levels	Distance from LDL-c goal according to EAS/ESC guidelines and the type of lipid lowering approach will be analyzed.	Baseline, 6 months and 12 months
Lipid Profile	This includes total cholesterol, HDL-C, and triglycerides. A measure of cumulative lipid exposure such as "Cholesterol Years" will be determined whenever available. The aim is to evaluate the overall impact of lipid- lowering therapies (LLTs) on the lipid profile and cardiovascular risk reduction.	Baseline, 6 months and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to Lipid-Lowering Therapies (LLTs)	Adherence will be assessed according to patients -report and the prescription data collected with Morisky Medication Adherence Scale - 8 items (MMAS-8). Total scores range from 0 to 8, with higher scores indicating better medication adherence. A score of 8 indicates high adherence, scores of 6 to <8 indicate medium adherence, and scores <6 indicate low adherence.	Baseline, 6 months and 12 months
Changes in Treatment Regimens	The evolution of LLT regimens will be monitored. Any modifications to the therapies, including dose adjustments or changes in medication, will be recorded and analyzed. Any drug discontinuation and change of treatment will be registered based on patients report.	6 months and 12 months
Patient Attitudes	Surveys conducted as per routine will capture insights into patient attitudes toward hypercholesterolemia treatments.	Baseline and 12 months
Clinical Practices	Surveys conducted as per routine will capture insights into new therapeutic evidence.	Baseline and 12 months

Collaborators and Investigators

• Sponsor: Fondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi)
• Collaborators: CMV-Stat S.r.l.

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 12, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 26, 2026

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cardiovascular risk; LDL Cholesterol; Real-world evidence; Lipid-Lowering Therapy; LDL-C goal attainment; Lipid Profil; Adherence to Lipid-Lowering Therapies; Changes in Treatment Regimens; Patient Attitudes and Clinical Practices
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hypercholesterolemia; Hyperlipoproteinemia Type II
• Other Study ID Numbers: TRAP-HC