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.

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