What question did this study set out to answer?

This trial aims to evaluate the effects of early LDL-C reduction with PCSK9 inhibitors in patients with acute coronary syndrome on plaque characteristics.

March 21, 2026Open Access

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

Key Points

This trial aims to evaluate the effects of early LDL-C reduction with PCSK9 inhibitors in patients with acute coronary syndrome on plaque characteristics.
Prospective, multicentre, open-label trial
Randomisation of 212 patients with ACS to either PCSK9 inhibitors plus statin or standard therapy for 6 months
Serial optical coherence tomography imaging of non-culprit coronary arteries
Primary endpoint: change in minimum fibrous cap thickness
Secondary endpoints: changes in lumen area, lipid arc, macrophage presence, LDL-C reduction.
Primary endpoint focuses on the change in fibrous cap thickness from baseline to 6 months
Expected improvements in plaque characteristics with early PCSK9i treatment
Secondary analyses will assess additional metrics of LDL-C reduction, plaque composition, and overall cardiovascular health.

Abstract

Introduction The ‘strike early and strike strong’ lipid-lowering strategy emphasises rapid reduction of low-density lipoprotein cholesterol (LDL-C) in patients with acute coronary syndrome (ACS). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are increasingly used alongside statins to achieve guideline-recommended LDL-C targets after ACS. However, despite substantial LDL-C reductions with early PCSK9i initiation, their effects on non-culprit coronary atherosclerotic plaques remain unclear. This study aims to assess the impact of early intensive LDL-C lowering with PCSK9i added to moderate-intensity statin therapy on optical coherence tomography (OCT)-derived plaque characteristics in non-culprit coronary lesions in patients with ACS. Methods and analysis In this prospective, multicentre, open-label trial, 212 patients with ACS will be randomised 1:1 to an early intensified lipid-lowering strategy (PCSK9i added to moderate-intensity statin) or guideline-directed medical therapy for 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 is the absolute change in minimum fibrous cap thickness within a matched target arterial segment from baseline to 6 months. Secondary endpoints include changes in minimum lumen area, maximum lipid arc, presence of macrophage infiltration, LDL-C reduction and achievement of LDL-C targets. The primary endpoint will be analysed using analysis of covariance, adjusting for treatment group, baseline LDL-C stratification (≥1.8 vs <1.8 mmol/L), and baseline minimum FCT. Secondary continuous outcomes will be analysed similarly, while categorical outcomes will be compared using chi-square, Fisher’s exact test or logistic regression, as appropriate. Ethics and dissemination Ethics approval was granted by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University (2024 Review No 1943). Results will be disseminated via peer-reviewed publications and presentations at academic conferences. Trial registration number NCT06791031 .

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