Lipoprotein(a) Levels in Patients With Atherosclerotic Cardiovascular Diseases in Russia

Not yet recruiting

• Conditions: Atherosclerotic Cardiovascular Disease
• Interventions: Drug: Atorvastatin; Drug: Simvastatin; Drug: Rozuvastatin; Drug: Ezetimibe; Drug: Niacin; Drug: Ciprofibrate; Drug: Fenofibrate; Drug: Bezafibrate; Drug: Evolocumab; Drug: Alirocumab; Drug: Inclisiran

• Registration Number: NCT06858332
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This study has the purpose to answer how the Lipoprotein(a) (Lp(a)) level is distributed among Atherosclerotic cardiovascular disease (ASCVD) patients in Russia, and what is the connection between elevated levels of this parameter and the cardiovascular disease (CVD) risk.

Detailed Description

This study will consist of several phases (consecutive stages):

Phase I: a cross-sectional study of Lp(a) level with ASCVD patients

Phase II:

* A non-interventional, prospective, cohort study with the phase I patients

* A cross-sectional study of Lp(a) levels with relatives of phase I patients

* A non-interventional, prospective, cohort study with patients' relatives

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-18
• Study First Submitted QC: 2025-03-03
• Last Update Submitted: 2025-03-03
• Study First Posted: 2025-03-05
• Last Update Posted: 2025-03-05
• Study Start: 2025-03-31
• Primary Completion: 2027-09-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 2382

Inclusion Criteria

1. Written informed consent (signed and dated).

2. Males and females aged ≥18 years.

3. Presence of one of the following ASCVDs for at least 3 months within the 2 years prior to signing the informed consent to participate in this study:

   • history of MI;
   • history of IS and/or TIA;
   • IHD confirmed by coronary angiography (stenosis ≥50%);
   • any revascularization surgery (emergency or planned), including CABG, PCI, carotid endarterectomy or carotid/intracranial stenting;
   • peripheral artery disease (intermittent claudication with ankle-brachial index ≤0.90 and/or lower limb amputation or revascularization in case of lower limb ischemia).

Exclusion Criteria

1. Acute infectious and inflammatory diseases, such as COVID-19, in the month leading up to the Screening visit.
2. Lp(a)-lowering therapy/methods (Lp(a) apheresis with PCSK9 inhibitors, inclisiran prior to the Screening visit) in the medical history before the Screening visit.
3. Participation in any interventional clinical study with investigational or marketed medicinal products at the time of enrollment.
4. Participation in other real-world clinical studies.
5. Stages 4 and 5 of chronic kidney disease (glomerular filtration rate CKD-EPI <30 mL/min/1.73 m2) and/or hepatic disease (total bilirubin: 2 × ULN).

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
ASCVD patients	Atorvastatin	Patients aged 18 and above with a history of ASCVD including peripheral arterial revascularization
ASCVD patients	Simvastatin	Patients aged 18 and above with a history of ASCVD including peripheral arterial revascularization
ASCVD patients	Rozuvastatin	Patients aged 18 and above with a history of ASCVD including peripheral arterial revascularization
ASCVD patients	Ezetimibe	Patients aged 18 and above with a history of ASCVD including peripheral arterial revascularization
ASCVD patients	Niacin	Patients aged 18 and above with a history of ASCVD including peripheral arterial revascularization
ASCVD patients	Ciprofibrate	Patients aged 18 and above with a history of ASCVD including peripheral arterial revascularization
ASCVD patients	Fenofibrate	Patients aged 18 and above with a history of ASCVD including peripheral arterial revascularization
ASCVD patients	Bezafibrate	Patients aged 18 and above with a history of ASCVD including peripheral arterial revascularization
ASCVD patients	Evolocumab	Patients aged 18 and above with a history of ASCVD including peripheral arterial revascularization
ASCVD patients	Alirocumab	Patients aged 18 and above with a history of ASCVD including peripheral arterial revascularization
ASCVD patients	Inclisiran	Patients aged 18 and above with a history of ASCVD including peripheral arterial revascularization
Relatives of the ASCVD patients	Atorvastatin	A first-degree relative of the ASCVD patient (patient's parents and children) with Lp(a) ≥125 nmol/L.
Relatives of the ASCVD patients	Simvastatin	A first-degree relative of the ASCVD patient (patient's parents and children) with Lp(a) ≥125 nmol/L.
Relatives of the ASCVD patients	Rozuvastatin	A first-degree relative of the ASCVD patient (patient's parents and children) with Lp(a) ≥125 nmol/L.
Relatives of the ASCVD patients	Ezetimibe	A first-degree relative of the ASCVD patient (patient's parents and children) with Lp(a) ≥125 nmol/L.
Relatives of the ASCVD patients	Niacin	A first-degree relative of the ASCVD patient (patient's parents and children) with Lp(a) ≥125 nmol/L.
Relatives of the ASCVD patients	Ciprofibrate	A first-degree relative of the ASCVD patient (patient's parents and children) with Lp(a) ≥125 nmol/L.
Relatives of the ASCVD patients	Fenofibrate	A first-degree relative of the ASCVD patient (patient's parents and children) with Lp(a) ≥125 nmol/L.
Relatives of the ASCVD patients	Bezafibrate	A first-degree relative of the ASCVD patient (patient's parents and children) with Lp(a) ≥125 nmol/L.
Relatives of the ASCVD patients	Evolocumab	A first-degree relative of the ASCVD patient (patient's parents and children) with Lp(a) ≥125 nmol/L.
Relatives of the ASCVD patients	Alirocumab	A first-degree relative of the ASCVD patient (patient's parents and children) with Lp(a) ≥125 nmol/L.
Relatives of the ASCVD patients	Inclisiran	A first-degree relative of the ASCVD patient (patient's parents and children) with Lp(a) ≥125 nmol/L.

Primary Outcome Measures

Name	Time	Method
Percentage of patients (%) with Lp(a) ≥125 nmol/L	Baseline	Percentage of patients (%) with Lp(a) ≥125 nmol/L at baseline
The difference in the number of patients with cardiovascular events (%) between the groups	24 months	The difference in the number of patients (%) with new cardiovascular events between the groups of patients with elevated Lp(a) ≥125 nmol/L and Lp(a) \<125 nmol/L

Secondary Outcome Measures

Name	Time	Method
Percentage of patients (%) with at least one CVD, and ASCVD number in different subgroups stratified by Lp(a) level	Baseline	Percentage of patients (%) with at least one CVD by Lp(a) level: ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L; \*CVD - Cardiovascular disease; ASCVD - Atherosclerotic cardiovascular disease
Percentage of ASCVD patients (%) in accordance with the Lp(a) level	Baseline	Percentage of ASCVD patients (%) by Lp(a) level: ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L
Age of patients at the time of the first ASCVD in different subgroups in accordance with the Lp(a) level	Baseline	Age of patients at the time of the first ASCVD in different subgroups by Lp(a) level: ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L
Percentage of patients (%) with disability groups I, II, and III in different subgroups stratified by the Lp(a) level	Baseline	Percentage of patients (%) with disability groups I, II, and III in different subgroups stratified by the Lp(a) level: ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L
Age of assignment of any disability group in different subgroups by the Lp(a) level	Baseline	Age of assignment of any disability group in different subgroups by the Lp(a) level: ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L
Duration of temporary incapacity (sick leave) following the onset of CVE in different subgroups based on Lp(a) level	Baseline	Duration of temporary incapacity (sick leave) following the onset of CVE (cardiovascular event) in different subgroups based on Lp(a) level: ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L
Percentage of patients (%) without an official disability status who had to completely stop working after developing CVE in different subgroups based on Lp(a) level	Baseline	Percentage of patients (%) without an official disability status who had to completely stop working after developing CVE (cardiovascular event) in different subgroups based on Lp(a) level: ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L
Lp(a) distribution level by a ASCVD type	Baseline	Percentage of patients with peripheral artery disease (PAD), ischemic stroke (IS), ischemic heart disease by the Lp(a) level\*; \*≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L
Percentage (%) of ASCVD patients with elevated Lp(a) levels by gender and age (20-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90 years)	Baseline	Percentage (%) of ASCVD patients with elevated Lp(a) levels by gender and age (20-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90 years)
Percentage of patients (%) with hemodynamically significant coronary atherosclerosis (stenosis ≥50%) in different subgroups by the Lp(a) level	Baseline	Percentage of patients (%) with hemodynamically significant coronary atherosclerosis (stenosis ≥50%) in different subgroups by the Lp(a) level ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L
Percentage of ASCVD patients (%) with elevated Lp(a) levels in groups stratified by the number of coronary arteries with hemodynamically significant stenosis in patients with relevant available data	Baseline	Percentage of ASCVD patients (%) with elevated Lp(a) levels in groups stratified by the number of coronary arteries with hemodynamically significant stenosis in patients with relevant available data
Percentage (%) of ASCVD patients with an elevated Lp(a) level classified depending on the presence of multifocal atherosclerosis, ischemic heart disease, and peripheral artery disease	Baseline	Percentage (%) of ASCVD patients with an elevated Lp(a) level classified depending on the presence of multifocal atherosclerosis, ischemic heart disease, and peripheral artery disease
Percentage of ASCVD patients (%) with elevated Lp(a) levels classified into groups with different numbers of MI events	Baseline	Percentage of ASCVD patients (%) with elevated Lp(a) levels classified into groups with different numbers of myocardial infarction (MI) events
Percentage of ASCVD patients (%) with elevated Lp(a) levels classified into groups with different numbers of IS and TIA events	Baseline	Percentage of ASCVD patients (%) with elevated Lp(a) levels classified into groups with different numbers of ischemic stroke (IS) and transient ischemic attack (TIA) events
Percentage of ASCVD patients (%) with elevated Lp(a) levels classified into groups with different types of hospitalization (planned/emergency)	Baseline	Percentage of ASCVD patients (%) with elevated Lp(a) levels classified into groups with different types of hospitalization (planned/emergency)
Percentage (%) of ASCVD patients with elevated Lp(a) levels classified by the first cardiovascular event (CVE)	Baseline	Percentage (%) of ASCVD patients with elevated Lp(a) levels classified by the first CVE (any of the following: myocardial infarction, ischemic stroke, transient ischemic attack, percutaneous coronary intervention, etc.)
Percentage of ASCVD patients (%) with elevated Lp(a) levels by the PCI number (planned/emergency)	Baseline	Percentage of ASCVD patients (%) with elevated Lp(a) levels by the percutaneous coronary intervention (PCI) number (planned/emergency)
Percentage of patients (%) with the first CVE (MI or IS) (before the Screening visit) in different subgroups by the Lp(a) level	Baseline	Percentage of patients (%) with the first CVE (MI or IS) (before the Screening visit) in different subgroups by the Lp(a) level ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L
Percentage of patients (%) with several CVEs (MI or IS) (before the Screening visit) in different subgroups by the Lp(a) level	Baseline	Percentage of patients (%) with several CVEs (MI or IS) (before the Screening visit) in different subgroups by the Lp(a) level ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L
Number of recurrent CVEs in different subgroups by the Lp(a) level	Baseline	Number of recurrent CVEs in different subgroups by the Lp(a) level ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L
Percentage of patients (%) with unstable angina, manifestations of TIA, PCI, and CABG in medical history (before the Screening visit) in different subgroups by the Lp(a) level	Baseline	Percentage of patients (%) with unstable angina, manifestations of transient ischemic attack (TIA), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG) in medical history (before the Screening visit) in different subgroups by the Lp(a) level ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L
Percentage of patients (%) with multiple CVE, such as unstable angina, TIA, PCI, and CABG (before or after the index/screening visit), in different subgroups based on Lp(a) level	Baseline	Percentage of patients (%) with multiple CVE, such as unstable angina, transient ischemic attack (TIA), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG) (before or after the index/screening visit), in different subgroups based on Lp(a) level ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L
Percentage of patients (%) with severe CVE (MI, IS) (after the index/screening visit) based on the Lp(a) level in different subgroups	3, 9, 12, 18, and 24 months	Percentage of patients (%) with severe CVE (MI, IS) based on the Lp(a) level ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L at 3, 9, 12, 18, and 24 months
Number of patients with recurrent CVEs (more than one event during the follow-up period) and the mean number of recurrent complications in the post-index visit period	3, 9, 12, 18, and 24 months	Number of patients with recurrent CVEs (more than one event during the follow-up period) and the mean number of recurrent complications at 3, 9, 12, 18, and 24 months
Percentage of patients (%) with cardiovascular deaths after the index/screening visit in different subgroups by the Lp(a) level	3, 9, 12, 18, and 24 months	Percentage of patients (%) with cardiovascular deaths in different subgroups by the Lp(a) level ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L at 3, 9, 12, 18, and 24 months
Percentage of patients who died after the index/screening visit in different subgroups by the Lp(a) level	3, 9, 12, 18, and 24 months	Percentage of patients who died in different subgroups by the Lp(a) level ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L at 3, 9, 12, 18, and 24 months
Percentage of patients (%) who needed emergency medical care or visited a medical facility during the period following the index/screening visit in different subgroups by the Lp(a) level	3, 9, 12, 18, and 24 months	Percentage of patients (%) who needed emergency medical care or visited a medical facility in different subgroups by the Lp(a) level ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L at 3, 9, 12, 18, and 24 months
Number of emergency visits or visits to a medical facility following the index/screening visit in various subgroups by the Lp(a) level	3, 9, 12, 18, and 24 months	Number of emergency visits or visits to a medical facility in various subgroups by the Lp(a) level ≤25 nmol/L, 25-75 nmol/L, 75-125 nmol/L, 125-188 nmol/L, 188-250 nmol/L, ≥250 nmol/L at 3, 9, 12, 18, and 24 months
Percentage of ASCVD patients (%) who achieved the target LDL-C level with the current lipid-lowering therapy	3, 9, 12, 18, and 24 months	Percentage of ASCVD patients (%) who achieved the target LDL-C level with the current lipid-lowering therapy
Percentage of ASCVD patients (%) receiving lipid-lowering therapy, who experienced a change in Lp(a) levels	3, 9, 12, 18, and 24 months	Percentage of ASCVD patients (%) receiving lipid-lowering therapy, who experienced a change in Lp(a) levels
Number of first-degree relatives (%) of patients with Lp(a) ≥125 nmol/	Baseline	Number of first-degree relatives (%) of patients with Lp(a) ≥125 nmol/L
Difference between groups in the number of relatives (%) with CVD complications during the 2-year observation period	24 months	The difference in the number of relatives (%) with new cardiovascular events between the groups of patients with elevated Lp(a) ≥125 nmol/L and Lp(a) \<125 nmol/L