PCSK9 inhibitoRs for Early Passivation of coRonary athEroSclerotic plaqueS in acute coronary syndromes (REPRESS): study protocol for a multicentre randomised controlled trial.

The REPRESS trial will randomise 212 patients with ACS in a 1:1 ratio to early intensified lipid-lowering or guideline-directed medical therapy.

• Patients will be randomised to either PCSK9 inhibitor added to moderate-intensity statin therapy or guideline-directed medical therapy.
• The treatment duration is 6 months.
• The trial is prospective, multicentre, and open-label in design.
• Ethics approval was granted by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University (2024 Review No 1943).
• The trial is registered as NCT06791031.

The primary endpoint of the REPRESS trial is the absolute change in minimum fibrous cap thickness within a matched target arterial segment from baseline to 6 months.

• Serial OCT imaging of non-culprit coronary arteries with 20-70% stenosis will be performed at baseline and 6 months.
• The primary endpoint will be analysed using analysis of covariance (ANCOVA), adjusting for treatment group, baseline LDL-C stratification (≥1.8 vs <1.8 mmol/L), and baseline minimum fibrous cap thickness.
• OCT-derived plaque characteristics in non-culprit coronary lesions are the focus of imaging assessment.

Secondary endpoints include multiple OCT-derived plaque characteristics as well as lipid-lowering outcomes.

• Secondary endpoints include changes in minimum lumen area, maximum lipid arc, and presence of macrophage infiltration.
• LDL-C reduction and achievement of LDL-C targets are also secondary endpoints.
• Secondary continuous outcomes will be analysed similarly to the primary endpoint using ANCOVA.
• Categorical outcomes will be compared using chi-square, Fisher's exact test, or logistic regression, as appropriate.

The trial addresses an evidence gap regarding the effect of early PCSK9 inhibitor initiation on non-culprit coronary atherosclerotic plaques in ACS patients.

• The 'strike early and strike strong' lipid-lowering strategy emphasises rapid reduction of LDL-C in patients with ACS.
• PCSK9 inhibitors are increasingly used alongside statins to achieve guideline-recommended LDL-C targets after ACS.
• Despite substantial LDL-C reductions with early PCSK9i initiation, their effects on non-culprit coronary atherosclerotic plaques remain unclear.
• Non-culprit lesions with 20-70% stenosis are specifically targeted for evaluation.