Abstract Body (Do not enter title and authors here): Introduction: Immune checkpoint inhibitors (ICI) are increasingly used to treat a wide variety of malignancies. The long-term cardiovascular risk profile of ICI therapy remains incompletely understood.

Methods: All patients at a single academic center receiving any ICI therapy between 2015 and 2023 were identified. Using ICD codes, we adjudicated major adverse cardiac events (MACE) after initiation of ICI therapy, defined as a composite endpoint of coronary artery disease (CAD), acute coronary syndrome (ACS), cardiomyopathy and heart failure (HF), arrhythmia, ischemic stroke, cardiac arrest, pericarditis, and myocarditis. Cancer type and baseline cardiometabolic risk factors were identified. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for all variables measured.

Results: Of patients receiving ICI therapy (n=5991), 1196 developed MACE, including ACS (n=152), stable CAD (n = 300), HF (n=217), arrhythmia (n=380), ischemic stroke (n=92), cardiac arrest (n=30) and myo- or pericarditis (n=25). Prior to a MACE event, patients received an average of 11.6 ± 12.7 ICI doses over 332.4 ± 448.0 days. Compared to the non-MACE group, those who developed MACE were older (OR 1.18, CI 1.09-1.27) and of male sex (OR 1.17, CI 1.00-1.23). They were more likely to have higher body mass index (BMI) (OR 1.13, CI 1.06-1.21), pre-existing hypertension (OR 1.3, CI 1.21-1.39), be on statin therapy (OR 1.19, CI 1.11-1.28) and have higher B-nauretic peptide (BNP) levels (OR 1.25, CI 1.06-1.47). Regarding cancer type, MACE was more likely to develop in those with melanoma (OR 1.11, CI 1.02-1.20), lung (OR 1.22, CI 1.11-1.34), colon (OR 1.08, CI 1.01-1.15), genitourinary (OR 1.19, CI 1.10-1.29), and prostate cancers (OR 1.08, CI 1.01-1.15). MACE was less likely to develop in breast cancer (OR 0.88, CI 0.80-0.96). All-cause mortality was higher in the MACE group (59.4% vs. 51.9%, p < 0.001).

Conclusion: Risk factors for developing MACE with ICI therapy include older age, male sex, cancer type, prior MACE, hypertension, statin use, and higher BMI and BNP. MACE is associated with higher all-cause mortality. These findings can assist in identifying and attenuating cardiovascular risk in patients undergoing ICI therapy.