Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®

NCT ID: NCT04313270

Last Updated: 2021-03-08

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 25 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-12-01
• Study Completion Date: 2025-12-01

Brief Summary

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®.

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.

Conditions

Hypercholesterolemia, Familial

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with FH starting a treatment with Evolocumab®

Evolocumab

Intervention Type: DRUG

12 weeks of treatment with Evolocumab

Interventions

Evolocumab

12 weeks of treatment with Evolocumab

Intervention Type: DRUG

Eligibility Criteria

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.)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federico II University

OTHER

Sponsor Role: lead

Responsible Party

Matteo Di Minno

Associate Professor of Internal Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Matteo Di Minno

Napoli, , Italy

Site Status: RECRUITING

Countries

Italy

Facility Contacts

Matteo Di Minno, MD

Role: primary

dario.diminno@hotmail.it

+390817464323

References

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.

Reference Type: DERIVED

PMID: 34991937 (View on PubMed)

Other Identifiers

2015/261

Identifier Type: -

Identifier Source: org_study_id