PCSK9 Inhibitors in the Progression of Aortic Stenosis

Study Overview
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Brief Summary
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Investigators plan evaluate whether PCSK9 inhibitors, a medication that can lower lipoprotein(a) and control dyslipidemia, can inhibit the progression of aortic stenosis, through a randomized controlled trial.

Detailed Description
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Aortic valve disease is the most common form of heart valve disease and is a major burden to society. Aortic valve disease is also expected to become more prevalent with the aging. Among aortic diseases, 'aortic stenosis (AS)', which is a narrowing of the aortic valve, and leads to symptoms of heart failure and sometimes death. For treatment of AS, the valve in replaced in a surgical to percutaneous method. Regardless of the method, valve replacement has its potential costs and complications that is an important issue that needs to be solved. Therefore, controlling the progression of AS and increasing the efficacy of medical therapy before valvular replacement is needed, is an important medico-social problem. Regarding the pathophysiology of AS, an elevation of lipoprotein(a) and dyslipidemia have been reported to be associated with the progression of cardiovascular calcification. PCSK9 inhibitors, which is a medication that can control both lipoprotein(a) and dyslipidemia may be a effective medication to control the progression of AS. Therefore, investigators will perform a randomized control trial, to compare the effect of PCSK9 inhibitors vs. placebo in its influence to AS progression.

Official Title
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Proprotein Convertase Subtilisin Kexin Type 9 Inhibitor in Aortic Stenosis

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Drug: PCSK9 Inhibitor [EPC]
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient agrees to participate in this study by signing the informed consent form. Alternatively, a legally authorized patient representative may agree to the patient's participation in this study and sign the informed consent form. The patient has a working diagnosis of aortic stenosis (mild to moderate), and has fair treatment compliance. Exclusion Criteria: Age under 19 years old Hypersensitivity to PCSK9 inhibitor LDL cholesterol < 70mg/dL at baseline Poor treatement compliance (The patient will need to visit the out-patient clinic every 2-weeks for medication) Positive pregnancy test or is known to be pregnant Any other reason the investigator deems the subject to be unsuitable for the study (e.g., Active malignant tumor, Any life-threatening condition with life expectancy less than 6months, etc.) Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the investigator, would preclude safe completion of the study

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, Double blind, Multi-center, Randomized clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PCSK9 inhibitor<br>Patients will receive bi-weekly PCSK9 inhibitor . | Drug: PCSK9 Inhibitor [EPC]<br>* Patients will receive PCSK9 inhibitor by a biweekly injection<br>|
| Placebo Comparator: Placebo<br>Patients will receive bi-weekly placebo. | Drug: Placebos<br>* Patients will receive Placebo by a biweekly injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of the Calcium score measured by cardiac CT (Agatston score) and by NaF PET | Calcium score progression in the PCSK9 inhibitor group and placebo group | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of inhibition in calcium score progression (Agatston score) by the presence of Lp(a) SNPs |  | 2 years | 
| Mean change in Lp(a) levels between treatment arms | Lp(a) levels will be measured in blood chemistry | 2 years | 
| Mean change in lipid panel (LDL, HDL, TG, Cholesterol) level | Lipid panels will be measured in blood chemistry | 2 years | 
| Aortic valve area measured by echocardiography |  | 2 years | 
| Aortic valve peak velocity measured by echocardiography |  | 2 years | 
| Any death event |  | 2 years | 
| Any cardiac death event |  | 2 years | 
| Any myocardial infarction event |  | 2 years | 
| Any revascularization for coronary artery disease |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aortic valve stenosis, PCSK9 inhibitor