Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®

Protein convertase subtilisin kexin type 9 (PCSK-9) inhibitors demonstrated efficacy in cholesterol reduction and in the prevention of cardiovascular events. The investigators will evaluate changes in lipid profile, oxidation markers and subclinical atherosclerosis in patients with familial hypercholesterolemia (FH) during 12 weeks of treatment with a PCSK-9 inhibitor, Evolocumab®.

Study Overview

• Status: Recruiting
• Conditions: Hypercholesterolemia, Familial
• Intervention / Treatment: Drug: Evolocumab

Detailed Description

Several studies emphasize the role of high levels of low-density lipoprotein cholesterol (LDL-C) as the main causative factor in atherosclerosis development. Among patients with hypercholesterolemia, those with very high levels of LDL-C exhibit increased prevalence of subclinical atherosclerosis and a higher atherosclerosis progression, thus leading to a significantly higher CV risk. Endothelial dysfunction is the earliest stage of the atherosclerotic process and even a trigger of CV events. Flow-mediated dilation (FMD) is widely accepted as an accurate and non-invasive method to assess vascular reactivity and, in turn, as a surrogate marker of subclinical atherosclerosis and an independent predictor of CV events. It's well known that hypercholesterolemia has been associated with decreased endothelial function and increased oxidative stress. Although statin treatment represented for years the gold standard as lipid lowering therapy, the target LDL-C is not always achieved, mainly among patients with very high levels of LDL-C. More recently, PCSK-9 inhibitors demonstrated efficacy in LDL-C reduction, in the prevention from CV events and in atherosclerotic burden regression. Some data showed an effect of PCSK-9 inhibitors on endothelial function, but no evidence is available on effect on LDL subfractions. Small dense LDL (sd-LDL) are considered an emerging risk factor for cardiovascular disease due to a greater atherogenic potential [ ] and are important markers for predicting CV risk.

• Study Type: Observational
• Enrollment (Anticipated): 25

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Recruiting
    • Matteo Di Minno
    • Contact: Matteo Di Minno, MD; Phone Number: +390817464323; Email: dario.diminno@hotmail.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

consecutive patients attending the lipid clinic of the Department of Clinical Medicine and Surgery, Federico II University Hospital with very high levels of LDL-C (above the 95th percentile when compared with a sex- and age-matched general population), normal triglyceride levels and presumed autosomal dominant transmission of hypercholesterolemia in the family were screened for inclusion in the present study

Description

Inclusion Criteria:

• diagnosis of FH (clinical and/or genetic)
• eligibility of patients to start a treatment with PCSK-9 according to 2016 ESC guidelines.

Exclusion Criteria:

• age < 18 years
• inability to understand or sign the informed consent
• high level of transaminases ( >3x upper normal limit)
• hypertriglyceridemia ( >150 mg/dl)
• end-stage renal disease (filtration rate < 30 ml/min/mq)
• current malignant disease or a diagnosis of malignancy in the 2 years prior to the first visit
• previous exposure to PCSK-9 inhibitors
• presence of hypercholesterolemia secondary to other causes (hypothyroidism, hormone therapies, corticosteroids etc.)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with FH starting a treatment with Evolocumab®	Drug: Evolocumab; 12 weeks of treatment with Evolocumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subclinical atherosclerosis	evaluation of subclinical atherosclerosis in patients receiving Evolocumab	12 weeks

Collaborators and Investigators

• Sponsor: Federico II University

Publications and helpful links

General Publications

• Iannuzzo G, Buonaiuto A, Calcaterra I, Gentile M, Forte F, Tripaldella M, Di Taranto MD, Giacobbe C, Fortunato G, Rubba PO, Di Minno MND. Association between causative mutations and response to PCSK9 inhibitor therapy in subjects with familial hypercholesterolemia: A single center real-world study. Nutr Metab Cardiovasc Dis. 2022 Mar;32(3):684-691. doi: 10.1016/j.numecd.2021.10.025. Epub 2021 Nov 11.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2017
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: March 15, 2020
• First Submitted That Met QC Criteria: March 17, 2020
• First Posted (Actual): March 18, 2020

Study Record Updates

• Last Update Posted (Actual): March 8, 2021
• Last Update Submitted That Met QC Criteria: March 4, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Atherosclerosis; Hyperlipoproteinemia Type II; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Evolocumab
• Other Study ID Numbers: 2015/261

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No