Impact of Optimal Pharmacotherapy on Lipid Profile and Qualitative Features of Atherosclerotic Plaques

NCT ID: NCT05639218

Last Updated: 2023-11-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-06-29

Study Completion Date

2023-12-31

Brief Summary

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Lipid accumulation, with mostly emphasized role of low-density lipoprotein cholesterol (LDL-C), is the pathogenetic cornerstone of atherosclerotic cardiovascular disease. Standard hypolipidemic therapy, based on statins and ezetimibe, does not always decrease LDL-C levels enough to achieve therapeutic goals. A novel and promising direction is inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) in hepatocytes, subsequently reducing LDL-C receptor degradation and increasing intracellular LDL-C uptake.

Aim of this study is to evaluate the effect of optimal hypolipidemic pharmacotherapy, including PCSK9 inhibitors and inclisiran, on plasma lipid profile and qualitative features of atherosclerotic plaques in very-high cardiovascular risk patients.

This study enrolls patients with an established atherosclerotic cardiovascular disease, receiving PCSK9 inhibitors or inclisiran as add-on treatment to statins in maximally tolerated dose and/or ezetimibe.

Effect of hypolipidemic pharmacotherapy is evaluated by analysis of plasma lipid profile parameter changes and qualitative features of atherosclerotic plaques using Near-Infrared Spectroscopy Intravascular Ultrasound Imaging (NIRS-IVUS) method.

Results of the study would be sufficient for complementing evidence regarding therapeutic strategy in very-high cardiovascular risk patients.

Detailed Description

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Background:

Lipid accumulation in artery walls is the pathogenetic cornerstone of atherosclerosis. The most commonly studied risk factor of atherosclerotic cardiovascular disease is low-density lipoprotein cholesterol (LDL-C), nevertheless other plasma lipids have an established role as well. LDL-C is considered the primary target for cardiovascular risk reduction, with therapeutic goal \<1.4 mmol/l in very-high cardiovascular risk patients with established atherosclerotic cardiovascular disease. Standard hypolipidemic therapy, based on statins and ezetimibe, is not always effective enough. Novel and promising direction is proprotein convertase subtilisin/kexin type 9 (PCSK9) - protease that binds LDL receptors in hepatocytes, subsequently promoting their lysosomal degradation. This process leads to reduced intracellular LDL-C uptake and increased LDL-C concentration in plasma. PCSK9 inhibitors - monoclonal antibodies evolocumab and alirocumab are successfully used in clinical practice, with a proven effectiveness in clinical trials ODYSSEY and FOURIER. An innovative medication is inclisiran - small interfering ribonucleic acid (siRNA) molecule that interferes with translation of messenger RNA (mRNA) of PCSK9 in hepatocytes as a result of complementary binding. Subsequently levels of synthesized PCSK9 are reduced, resulting in positive impact on plasma lipid profile. Inclisiran has demonstrated remarkable efficacy and safety profile in ORION clinical trials, being registered in European Medicines Agency since year 2020. Real-world data regarding optimal lipid-lowering pharmacotherapy, including experience with new medications, is of great clinical interest, studying effect on plasma lipid profile, as well as qualitative features of atherosclerotic plaques using Near-Infrared Spectroscopy Intravascular Ultrasound Imaging (NIRS-IVUS) method.

Aim:

Aim of this study is to evaluate effect of optimal hypolipidemic pharmacotherapy on plasma lipid profile and and qualitative features of atherosclerotic plaques in very-high cardiovascular risk patients receiving PCSK9 inhibitors or inclisiran as add-on treatment to statins in maximally tolerated dose and/or ezetimibe.

Study design:

Prospective observational study.

Study population:

Very-high cardiovascular risk patients with an established atherosclerotic cardiovascular disease, receiving PCSK9 inhibitors or inclisiran as add-on treatment to statins in maximally tolerated dose and/or ezetimibe in the context of optimal hypolipidemic pharmacotherapy, in whom NIRS-IVUS investigation has been performed.

Data acquisition:

Patients fulfilling eligibility criteria and agreeing to participate in the study are included. Baseline demographic and medical data is acquired, with subsequent follow-up ambulatory visits after 3 and 6 months after PCSK9 inhibitor or inclisiran therapy initiation. After 15 months since inclusion, follow-up with NIRS-IVUS performed is foreseen. For analysis of obtained data MS Excel and IBM SPSS Statistics software is used.

Clinical implications:

Results of this study would be of high clinical interest for complementing evidence and improving outcomes regarding therapeutic strategy in very-high cardiovascular risk patients with an established atherosclerotic cardiovascular disease.

Conditions

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Atherosclerotic Cardiovascular Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Inclisiran

Patients are receiving PCSK9 inhibitors or inclisiran in the context of optimal hypolipidemic pharmacotherapy

Intervention Type DRUG

Other Intervention Names

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PCSK9 inhibitor

Eligibility Criteria

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Inclusion Criteria

* Very high cardiovascular risk - documented atherosclerotic cardiovascular disease
* On maximally tolerated statin and/or ezetimibe therapy for at least 1 month LDL-C treatment target \<1.4 mmol/l not achieved
* Receiving PCSK9 inhibitor or inclisiran as add-on treatment to maximally tolerated statin dose and/or ezetimibe in the context of optimal pharmacotherapy
* NIRS-IVUS performed (written informed consent for the procedure signed according to regulations in the hospital)
* Available blood test results - plasma lipid profile
* Patient agrees to participate in the study (signed informed consent)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pauls Stradins Clinical University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Karlis Trusinskis

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Karlis Trusinskis, MD

Role: PRINCIPAL_INVESTIGATOR

Pauls Stradins Clinical University Hospital

Locations

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Pauls Stradins Clinical University Hospital

Riga, , Latvia

Site Status

Countries

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Latvia

Other Identifiers

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PCSK9I-0621

Identifier Type: -

Identifier Source: org_study_id