PCSK9 inhibitoRs for Early Passivation of coRonary athEroSclerotic plaqueS in Acute Coronary Syndromes (REPRESS)

PCSK9 inhibitoRs for Early Passivation of coRonary athEroSclerotic plaqueS in Acute Coronary Syndromes (REPRESS): Study Protocol for a Multicenter Randomized Controlled Trial

In this prospective, multicenter, open-label trial, 212 ACS patients will be randomized 1:1 to either the "PCSK9i early" intensified therapy group (initial addition of PCSK9i to moderate-intensity statin) or the guideline-directed medical therapy group for 6 months. Serial OCT imaging of non-culprit arteries (20-70% stenosis) is performed at baseline and 6 months. The primary endpoint is the absolute change in minimum fibrous cap thickness at 6 months, and secondary endpoints including changes in lumen area, lipid arc, macrophage infiltration, LDL-C reduction, and target LDL-C achievement.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: PCSK9 inhibitor (PCSK9i)

• Study Type: Interventional
• Enrollment (Estimated): 212
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhongxiu Chen; Phone Number: 18030708238; Email: czxlfb1988@163.com
• Study Contact Backup: Name: Yong He; Phone Number: 18980602038; Email: heyongmd@wchscu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female, age ≥ 18 years at screening
• Acute coronary syndrome who underwent PCI of the culprit lesions.
• Non-culprit vessel (target vessel) meets the following criteria after culprit vessel PCI:
• Target vessel diameter > 2.5 mm, suitable for OCT examination
• Target vessel with angiographically estimated stenosis (diameter stenosis 20-70%)
• Target vessel must be native coronary arteries, vessel segment without previous PCI
• Target vessel cannot be a venous or arterial bridge vessel
• Ability to cooperate the requirements of the study and to offer written informed consent
• Willingness to complete follow-up visits and examinations as required by the schedule
• Life expectancy > 1 year

Exclusion Criteria:

• Left main disease of non-culprit artery, defined as ≥ 50% reduction in lumen diameter of the left main coronary artery via angiographic visual estimation
• Thrombotic target lesion, severe calcification or tortuosity lesions unfavorable for OCT examination
• Coronary artery anatomy that prevents complete imaging of the segment of interest (including at least 5 mm of both edges of the stenosis)
• True bifurcation lesions requiring stenting
• TIMI flow < 2 of the culprit-related arteries after PCI
• Unstable clinical status (cardiogenic shock, hemodynamic or electrical instability)
• Advanced heart failure (New York cardiac class III-IV)
• Ischaemic stroke within the past 6 months or cerebral haemorrhage at any time in the past
• Severe valvular disease or valvular disease that may require surgery or percutaneous valve replacement
• Diffuse coronary artery lesions or the presence of ≥ 1 untreated non-culprit lesion (non-culprit flow-restricting lesion planned for near-term, phase II PCI)
• Target vessel with coronary artery bypass grafting or PCI
• Planned major surgery requiring interruption of dual-antiplatelet therapy
• Statin intolerance and patients unsuitable for statin therapy with alanine aminotransferase greater than 3 times the upper limit of normal or creatine kinase greater than 3 times the upper limit of normal (not attribute to an acute MI) or greater
• Familial hypercholesterolaemia
• Prior (within 180 days prior to the first study visit) exposure to PCSK9i, either as an experimental or marketed drug
• Female subjects of childbearing potential, defined as all female subjects who are physiologically capable of becoming pregnant, unless such female subjects are using an effective method of contraception during the trial
• Women who are pregnant or breastfeeding or intend to become pregnant
• Comorbidities with malignancies, active infections, or major hematologic, metabolic, or endocrine disorders are judged unsuitable by the investigator
• Severe hepatic insufficiency (Child-Pugh class C)
• Severe renal dysfunction (estimated glomerular filtration rate < 30 mL/min/1.73 m2)
• Current enrollment in another investigational device or drug study
• Poor adherence and unable to complete the expected follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: "PCSK9i early" intensified therapy group; Initial addition of PCSK9i to moderate-intensity statin	Drug: PCSK9 inhibitor (PCSK9i); Patients randomized to the "PCSK9i early" intensified therapy group will receive initial treatment with a PCSK9 inhibitor-either evolocumab 140 mg or alirocumab 75 mg, both administered subcutaneously every two weeks with the initial dose given during hospitalization and subsequent doses self-administered at home-or inclisiran sodium 300 mg (equivalent to 284 mg inclisiran), administered by healthcare professionals at baseline and again at the 3-month study visit. All patients will receive moderate-intensity statin, including atorvastatin 20 mg or rosuvastatin 10 mg. The intervention will be initiated during hospitalization for the index ACS event, within 24 hours of randomization, irrespective of baseline LDL-C levels or prior statin use.
No Intervention: Guideline-directed medical therapy group; Stepwise lipid-lowering strategies based on the 2025 American College of Cardiology/American Heart Association guidelines for ACS, Chinese Lipid Management Guidelines (2023), and Expert Consensus on Clinical Pathways for Lipid Management in Chinese Patients with ACS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in the minimum fibrous cap thickness of target lesions	Absolute change in the minimum fibrous cap thickness of target lesions from baseline to 6 months.	At 6 months post randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in minimum fibrous cap thickness of target vessels	Percent change in minimum fibrous cap thickness of target vessels from baseline to 6 months.	At 6 months post randomization
Absolute change in mean minimum fibrous cap thickness across target vessels	Absolute change in mean minimum fibrous cap thickness across target vessels from baseline to 6 months.	At 6 months post randomization
Absolute changes in minimum lumen area of target vessels	Absolute changes in minimum lumen area of target vessels from baseline to 6 months.	At 6 months post randomization
Absolute changes in maximum lipid arc of target vessels	Absolute changes in maximum lipid arc of target vessels from baseline to 6 months.	At 6 months post randomization
Presence of macrophage infiltration in target vessels	Presence of macrophage infiltration in target vessels from baseline to 6 months.	At 6 months post randomization
Proportion of patients with OCT-identified vulnerable plaques	Proportion of patients with OCT-identified vulnerable plaques (defined as FCT < 75 µm plus at least two of three features: lipid arc > 180°, MLA < 3.5 mm², and macrophage infiltration) from baseline to 6 months.	At 6 months post randomization
Change in total cholesterol	Change in total cholesterol from baseline to 3 and 6 months.	At 3 months and 6 months post randomization
Change in apolipoprotein B	Change in apolipoprotein B from baseline to 3 and 6 months.	At 3 months and 6 months post randomization
Change in lipoprotein(a)	Change in lipoprotein(a) from baseline to 3 and 6 months.	At 3 months and 6 months post randomization
Change in triglycerides	Change in triglycerides from baseline to 3 and 6 months.	At 3 months and 6 months post randomization
Change in very low-density lipoprotein cholesterol	Change in very low-density lipoprotein cholesterol from baseline to 3 and 6 months.	At 3 months and 6 months post randomization
Change in low-density lipoprotein cholesterol	Change in low-density lipoprotein cholesterol from baseline to 3 and 6 months.	At 3 months and 6 months post randomization
Change in high-density lipoprotein cholesterol	Change in high-density lipoprotein cholesterol from baseline to 3 and 6 months.	At 3 months and 6 months post randomization
Proportion of patients achieving predefined LDL-C targets	Proportion of patients achieving predefined LDL-C targets (< 1.4 mmol/L) from baseline to 3 and 6 months.	At 3 months and 6 months post randomization
Adherence to lipid-lowering therapy	Adherence (proportion of days covered) to lipid-lowering therapy (statin, cholesterol absorption inhibitor, and PCSK9i) from baseline to 3 months and 6 months.	At 3 months and 6 months post randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of major adverse cardiovascular events (MACEs)	MACEs are defined as the composite of cardiac death, nonfatal myocardial infarction, nonfatal stroke, and ischemia-driven revascularization.	At 6 months and 12 months post randomization
Incidence of bleeding events	Bleeding events are defined according to the Academic Research Consortium (ARC) criteria.	At 6 months and 12 months post randomization
Change in high-sensitivity C-reactive protein	Change in high-sensitivity C-reactive protein from baseline to 3 and 6 months.	At 3 months and 6 months post randomization
Change in Interleukin-6 (IL-6)	Change in IL-6 levels from baseline to 3 and 6 months.	At 3 months and 6 months post randomization
Change in tumor necrosis factor-alpha (TNF-α)	Change in TNF-α levels from baseline to 3 and 6 months.	At 3 months and 6 months post randomization
Change in absolute T-cell count	Change in absolute T-cell count from baseline to 3 and 6 months.	At 3 months and 6 months post randomization
Change in absolute B-cell count	Change in absolute B-cell count from baseline to 3 and 6 months.	At 3 months and 6 months post randomization
Change in absolute natural killer (NK) cell count	Change in absolute NK cell count from baseline to 3 and 6 months.	At 3 months and 6 months post randomization

Collaborators and Investigators

• Sponsor: West China Hospital
• Investigators: Principal Investigator: Yong He, Department of Cardiology, West China Hospital of Sichuan University

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: January 11, 2025
• First Submitted That Met QC Criteria: January 18, 2025
• First Posted (Actual): January 24, 2025

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Coronary Artery Disease
• Other Study ID Numbers: WestChinaH-CVD-009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD that will be shared include anonymized data on baseline characteristics, primary and secondary outcome measures.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No