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Intensifying lipid-lowering with evinacumab to reduce coronary plaque in homozygous familial hypercholesterolemia

Assessing the Impact of Intensification of Lipid Lowering Therapy With Guidelines-based Evinacumab Administration on Coronary Plaque Volumes Measured by Coronary Computed Tomography Angiography (CCTA) in Patients With Homozygous Familial Hypercholesterolemia (HoFH): A Real World, Prospective and Retrospective, Observational Study

Observational Fondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi) · NCT07447648

This project will test whether adding evinacumab to existing lipid-lowering therapy can shrink or slow coronary plaque buildup in people with homozygous familial hypercholesterolemia using CCTA imaging.

Quick facts

Study typeObservational
Enrollment52 (estimated)
Ages12 Years and up
SexAll
SponsorFondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi) Academic / other
Drugs / interventionsEvinacumab
Locations13 sites (Paris and 12 other locations)
Trial IDNCT07447648 on ClinicalTrials.gov

What this trial studies

This is a multicenter, international, observational study using both retrospective and prospective data to compare HoFH patients who received intensified lipid-lowering that includes evinacumab with those on conventional therapy. Coronary computed tomography angiography (CCTA) is used to quantify total plaque volume and differentiate plaque types at baseline and 18–24 months follow-up. Participants are recruited from about 25 European centers and include adolescents and adults meeting consensus diagnostic criteria for HoFH, with specific imaging availability requirements. The study leverages real-world clinical care to describe how adding an ANGPTL3 antibody affects plaque burden outside of randomized trials.

Who should consider this trial

Good fit: Ideal candidates are patients with a clinical or genetic diagnosis of HoFH aged ≥12 years (≥18 in some countries) who started evinacumab within the past 24 months, remained on stable background lipid therapy, and have both baseline and 18–24 month follow-up CCTA available.

Not a fit: Patients without baseline or follow-up CCTA, those who have not received evinacumab as an add-on to stable lipid therapy, or those with clinical conditions that preclude reliable CCTA assessment are unlikely to be included or derive direct information from this study.

Why it matters

Potential benefit: If successful, this work could show that adding evinacumab to existing therapy reduces coronary plaque burden and potentially lowers future cardiovascular risk for patients with HoFH.

How similar studies have performed: Randomized trials and registries have shown evinacumab produces large LDL-C reductions in HoFH, but systematic, real-world imaging evidence of its effect on coronary plaque volume remains limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria (intensified treatment group - Evinacumab):

1. Willing and able to provide written informed consent form/assent form for the use of retrospective and prospective data.
2. Male or female patients aged ≥12 years old at time of enrolment (exception for Italy and France ≥18 years).
3. Clinical or genetic diagnosis of Homozygous Familial Hypercholesterolemia (HoFH) according to the consensus statement by Cuchel et al, 2023; EHJ (14).
4. Patients who initiated Evinacumab (at the approved dosage and administration) within 24 months before enrolment as add-on to lipid-lowering treatment (with statins, ezetimibe, PCSK9i and/or other agents or treatment) at stable dose for at least 30 days before Evinacumab initiation, as per routine clinical care and no change in dosing is anticipated.
5. Availability of a baseline CCTA performed at least 6 months prior or 1 month after Evinacumab initiation and a follow-up CCTA performed 18-24 months after Evinacumab initiation.
6. LDL-cholesterol ≥ 140 mg/dl (3.5 mmol/L) despite lipid-lowering treatment.

Inclusion criteria (conventional treatment group - No Evinacumab)

1. Willing and able to provide written informed consent form/assent form for the use of retrospective and prospective data.
2. Male or female patients aged ≥12 years old at time of enrolment (exception for Italy and France ≥18 years).
3. Clinical or genetic diagnosis of Homozygous Familial Hypercholesterolemia (HoFH) according to the consensus statement by Cuchel et al, 2023; EHJ (14).
4. Patients with HoFH on standard lipid-lowering therapy (statins, ezetimibe, PCSK9i and/or other agents or treatment) at stable dose for at least 30 days before a baseline CCTA and with a follow-up CCTA after 18-24 months from the baseline one.

   * Required lipid lowering therapies: statin, ezetimibe and PCSK9 directed therapy (unless discontinuation due to \<15% LDL-cholesterol reduction).
   * Optional additional lipid-lowering therapies:
   * Lipoprotein apheresis, at stable intervals for at least 3 months.
   * Lomitapide, at stable dose for at least 3 months.
5. LDL-cholesterol ≥ 140 mg/dl (3.5 mmol/L) despite lipid-lowering treatment.

Exclusion criteria (intensified treatment group - Evinacumab)

1. Patients participating in a clinical trial with an investigational drug within the last 6 months.
2. Patients treated outside of Evinacumab approved indication.
3. Inability to access adequate retrospective clinical data from medical records.
4. Inability or unwillingness to provide informed consent/assent or refusal to participate.
5. Previous multi-vessel coronary artery bypass grafting (CABG). Patients with single-vessel CABG are not excluded.
6. Pregnancy at the time of the LLT administration.
7. Moderate to severe renal impairment, or end-stage renal disease (ESRD) undergoing kidney transplantation or chronic renal replacement therapy.

Exclusion criteria (conventional treatment group - No Evinacumab)

1. Participation in any interventional clinical trial involving investigational drugs within the last 6 months.
2. Inability to access adequate retrospective clinical data from medical records.
3. Inability or unwillingness to provide informed consent/assent or refusal to participate.
4. Previous multi-vessel coronary artery bypass grafting (CABG). Patients with single-vessel CABG are not excluded.
5. Moderate to severe renal impairment, or end-stage renal disease (ESRD) undergoing kidney transplantation or chronic renal replacement therapy.
6. Pregnancy at the time of the LLT administration.

Where this trial is running

Paris and 12 other locations

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Homozygous Familial HypercholesterolemiaCoronary Computed Tomography AngiographyEvinacumabCardiovascular DiseaseLDL CholesterolLipid-Lowering TherapyLipid Metabolism DisordersAtherosclerosis
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.