Effects of Icosapent Ethyl on Coronary Plaque, Inflammation, and Ventricular Remodeling

Impact of Icosapent Ethyl on Ventricular Remodeling, Inflammation, and Coronary Plaque Stability in Patients With Acute or Chronic Coronary Syndrome: A Prospective, Observational, Real-World Study

Even with standard treatments like statins, patients with coronary artery disease often face a residual risk of further heart events. This risk is largely driven by ongoing inflammation and unstable fatty plaques in the heart's blood vessels. Icosapent ethyl (IPE) is a highly purified prescription medication known to improve cardiovascular outcomes, but its detailed effects on the heart's structure and inflammation in everyday clinical practice need further exploration.

This study is a prospective, observational, real-world study designed to evaluate the effectiveness of IPE in patients with Acute Coronary Syndrome (ACS) or Chronic Coronary Syndrome (CCS). The study plans to enroll 420 patients who will be followed for 12 months. Based on their routine clinical prescriptions, participants will be grouped into a control group (receiving standard cardiovascular care, including statins) and an exposure group (receiving standard care plus IPE).

Throughout the 1-year follow-up, researchers will conduct regular blood tests and advanced heart imaging. The main goal is to determine if adding IPE to standard therapy leads to a more significant reduction in inflammation. Additionally, the study will observe how IPE affects the stability of coronary plaques and the healing process of ventricular remodeling in a real-world clinical setting.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease; Inflammation; Ventricular Remodeling; Chronic Coronary Syndrome; Atherosclerosis Cardiovascular Disease; Acute Coronary Syndromes (ACS)

• Study Type: Observational
• Enrollment (Estimated): 420

Contacts and Locations

• Study Contact: Name: Yueying Wang; Phone Number: +86 18202513787; Email: wangyueying9228@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult patients (aged 18 years and older) diagnosed with either acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) who present to the cardiology inpatient wards or outpatient clinics of the participating medical centers. These are real-world patients who have elevated fasting triglyceride levels (>= 1.7 mmol/L) and are routinely receiving standard-of-care cardiovascular therapies, including statin therapy. Depending on their routine clinical prescriptions determined by their treating physicians, they are either receiving Icosapent ethyl (IPE) as an add-on therapy or continuing with standard of care alone.

Description

Inclusion Criteria:

• Age 18 years and older, of any sex.

  • Definite diagnosis of chronic coronary syndrome (CCS) according to the Chinese Guidelines for the Diagnosis and Management of Patients with Chronic Coronary Syndrome, or acute coronary syndrome (ACS) according to the 2025 ACC/AHA/ACEP/NAEMSP/SACI Guideline for the Management of Acute Coronary Syndromes.
  • Laboratory evaluation showing fasting triglycerides (TG) >= 1.7 mmol/L.
  • Ability to fully understand the study purpose, voluntary participation, and provision of signed written informed consent.

Exclusion Criteria:

• Women who are planning a pregnancy, currently pregnant, or lactating.

  • Known hypersensitivity or allergic reaction to the active ingredient of icosapent ethyl (IPE) or any of its excipients (applicable to patients in the exposure cohort).
  • Diagnosed with major life-threatening conditions such as malignant tumors, end-stage lung disease, or advanced neurodegenerative diseases, with a life expectancy of less than 12 months.
  • Concurrent participation in any other interventional clinical trial involving investigational drugs or medical devices.
  • Any other condition or severe non-compliance that, in the judgment of the investigator, makes the patient unsuitable for enrollment in this study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Exposure Cohort; atients with acute or chronic coronary syndrome who are prescribed Icosapent ethyl (IPE) in addition to their standard of care (including statin therapy).
Control Cohort; Patients with acute or chronic coronary syndrome receiving standard of care (including statin therapy) only, without Icosapent ethyl.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Systemic Inflammatory Markers (hs-CRP, IL-6, and sST2)	Evaluate the relative and absolute changes in systemic inflammation and cardiac stress markers, including high-sensitivity C-reactive protein (hs-CRP), Interleukin-6 (IL-6), and soluble suppression of tumorigenicity 2 (sST2).	Baseline, 1 month, 6 months, and 12 months
Change from Baseline in Vulnerable Plaque Markers (Lp-PLA2 and UACR)	Evaluate the changes in cardiovascular and microvascular vulnerability markers, specifically Lipoprotein-associated phospholipase A2 (Lp-PLA2) and Urinary albumin-to-creatinine ratio (UACR).	Baseline, 1 month, 6 months, and 12 months
Change from Baseline in Lipid Profile Parameters	Assess changes in lipid metabolism parameters, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB), and Lipoprotein(a) [Lp(a)].	Baseline, 1 month, 6 months, and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Echocardiographic Parameters of Ventricular Remodeling	Evaluate structural and functional changes of the left ventricle by calculating Left Ventricular End-Diastolic Volume (LVEDV) and Left Ventricular End-Systolic Volume (LVESV) via transthoracic echocardiography.	Baseline, 1 month, 6 months, and 12 months
Change from Baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP)	Evaluate changes in the myocardial wall stress and heart failure biomarker NT-proBNP.	Baseline, 1 month, 6 months, and 12 months
Change in Coronary Plaque Morphology and Stenosis Evaluated by Coronary CTA	Change in Coronary Plaque Maximum Thickness Evaluated by CTA (Unit: mm)	Baseline and 9 or 12 months
Change in Coronary Plaque Morphology and Stenosis Evaluated by Coronary CTA	Change in Coronary Plaque Length Evaluated by CTA (Unit: mm)	Baseline and 9/12 months
Change in Coronary Plaque Morphology and Stenosis Evaluated by Coronary CTA	Change in Coronary Plaque Area Evaluated by CTA (Unit: mm^2)	Baseline and 9/12 months
Change in Coronary Plaque Morphology and Stenosis Evaluated by Coronary CTA	Change in Degree of Coronary Luminal Stenosis Evaluated by CTA (Unit: percentage)	Baseline and 9/12 months
Change in Coronary Plaque Morphology and Stenosis Evaluated by Coronary CTA	Change in Proportion of Hypoechoic Plaque Components Evaluated by CTA (Unit: percentage)	Baseline and 9/12 months
Change from Baseline in Glucose Metabolism Parameters in the Diabetic Subpopulation	Evaluate changes in Fasting Blood Glucose (FBG) among participants with a history of diabetes.	Baseline, 1 month, 6 months, and 12 months
Change from Baseline in Glucose Metabolism Parameters in the Diabetic Subpopulation	Evaluate changes in Insulin (INS) among participants with a history of diabetes.	Baseline, 1 month, 6 months, and 12 months
Change from Baseline in Glucose Metabolism Parameters in the Diabetic Subpopulation	Evaluate changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) among participants with a history of diabetes.	Baseline, 1 month, 6 months, and 12 months
Change from Baseline in Glucose Metabolism Parameters in the Diabetic Subpopulation	Evaluate changes in Hemoglobin A1c (HbA1c) among participants with a history of diabetes.	Baseline, 1 month, 6 months, and 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Adverse Cardiovascular Events (MACE)	Assess the between-group differences in the composite incidence of MACE, defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, heart failure hospitalization, and unplanned revascularization.	Up to 12 months
Adverse Events (AEs) and Serious Adverse Events (SAEs)	Safety endpoint evaluating the occurrence of all-cause adverse events, serious adverse events, and specific safety events of interest (including clinical bleeding events) during the study medication period.	Up to 12 months

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Publications and helpful links

General Publications

• Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019 Jan 3;380(1):11-22. doi: 10.1056/NEJMoa1812792. Epub 2018 Nov 10.

Study record dates

Study Major Dates

• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): May 30, 2029

Study Registration Dates

• First Submitted: May 25, 2026
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 11, 2026

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Anatomical; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Pathological Conditions, Signs and Symptoms; Inflammation; Coronary Artery Disease; Acute Coronary Syndrome; Ventricular Remodeling
• Other Study ID Numbers: 2026-358

Plan for Individual participant data (IPD)

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

IPD Plan Description

De-identified individual participant data (IPD) that underlie the results reported in the primary publication, along with the study protocol and statistical analysis plan, will be shared.

Data will be available upon reasonable request to the Principal Investigator, beginning 6 months and ending 36 months following article publication.

To gain access, researchers must submit a methodologically sound proposal for secondary analysis or meta-analysis. The proposal will be reviewed by the study steering committee. If approved, data sharing will be strictly subject to a formal data-sharing agreement and must comply with the ethical regulations of the participating institutions. No specific IPD will be shared unconditionally.

Drug and device information, study documents

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