Proactive, short-term PCSK9 inhibition after PCI in patients with coronary artery disease at high residual risk: rationale and design of the randomized HANYANG-PICK trial.

BACKGROUND: Despite advances in stent design and PCI optimization, stent failure remains clinically relevant in patients with coronary artery disease. This process is primarily driven by vascular injury and maladaptive healing, leading to neointimal hyperplasia, neoatherosclerosis, and recurrent ischemic events. A subset of patients remains vulnerable despite angiographically successful PCI, reflecting residual risk not fully captured by procedural assessment alone. Novel strategies to reduce this residual risk are therefore warranted. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, beyond potent LDL-C reduction, have demonstrated plaque-stabilizing effects. Preclinical data suggest that PCSK9 promotes proinflammatory cytokine release, vascular smooth muscle cell proliferation, and impaired endothelial repair-mechanisms implicated in adverse vascular responses after PCI.

AIM: To determine whether proactive, short-term evolocumab improves outcomes in patients with coronary artery disease at high residual risk after PCI.

METHODS: The HANYANG-PICK trial is a prospective, randomized, open-label, multicenter study enrolling patients with post-PCI maxLCBI4mm ≥200 on NIRS-IVUS. Participants will be randomized 1:1 to standard care or standard care plus evolocumab 140 mg subcutaneously within 24 h of PCI and at 2 weeks. The primary endpoint is the composite of all-cause death, myocardial infarction, stroke, or any clinically driven revascularization at 12 months.

ETHICS AND DISSEMINATION: The protocol has been approved by the Institutional Review Board of all participating centers. Written informed consent will be obtained from all participants. Results will be disseminated in peer-reviewed journals and at scientific conferences.

CONCLUSIONS: The HANYANG-PICK trial is an exploratory, hypothesis-generating randomized study designed to test whether proactive, short-term PCSK9 inhibition initiated during the early post-PCI period can reduce adverse outcomes in patients with high residual risk identified by post-PCI intravascular imaging.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT07084259, Identifier NCT07084259.