Objective To explore the clinical characteristics and prognostic factors of acute coronary syndrome (ACS) in patients receiving immune checkpoint inhibitor (ICI) treatment, and to inform safer medication practices in oncology.

Methods A retrospective analysis was conducted on 41 patients happened ACS during ICI treatment or follow-up at The Fourth Hospital of Hebei Medical University between January 2020 and January 2025. The clinical features, prognosis, and prognostic risk factors associated with ICI-ACS were analyzed.

Results Among 41 ICI-ACS patients, 21(51.2%) experienced other immune-related adverse events with 2 ICI-associated myocarditis. Twenty-eight patients (68.3%) presented with multi-vessel coronary artery disease, often accompanied by a high thrombotic burden. Fifteen patients (36.6%) subsequently developed major adverse cardiovascular events (MACEs), with acute heart failure being the most common (22.0%, 9/41). Multivariate logistic regression analysis revealed targeted therapies and elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) level were associated with a worse prognosis of ICI-ACS patients.

Conclusions ICI-ACS is relatively rare but serious, with a poor prognosis. Clinical vigilance and cardiovascular monitoring during immunotherapy should be enhanced. Further research is needed to identify reliable biomarkers for risk stratification and prognostic evaluation of ICI-ACS.