Real-world analysis of cardiovascular adverse events and risk factors after immune checkpoint inhibitor therapy

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, offering significant survival benefits across diverse malignancies. However, growing evidence suggest an increased occurrence of cardiovascular adverse events (CVAEs) following ICI, which remain poorly characterized in large, real-world populations.

To quantify the incidence and spectrum of CVAEs following ICI initiation and identify demographic, clinical, and treatment-related risk factors for CVAE development.

We conducted a retrospective cohort study using electronic health record data from the OneFlorida + Clinical Research Network. Adult cancer patients (≥ 18 years) with cancer who started FDA-approved ICIs between January 1, 2018, and December 31, 2023, were included. Eligible patients had either ≥ 1 inpatient or ≥ 2 outpatient encounters after. The primary outcome was new-onset CVAE within one year. Kaplan-Meier survival analyses and multivariable Cox regression evaluated associations with risk factors.

Among 9,541 patients initiating ICIs, 2,320 (24.3%) developed a CVAE within one year, with arrhythmia (15.7%), heart failure (5.2%), and stroke (4.1%) being the most common. Cardiometabolic comorbidities (hypertension, hyperlipidemia, diabetes, and obesity) were independently associated with increased CVAE risk. CVAE incidence varied significantly by cancer type, with highest risk observed in breast, liver, and lung cancers compared to melanoma. Triple checkpoint blockade (CTLA-4 + PD-(L)1 + LAG-3) conferred a modest but significant increase in CVAE risk.

CVAEs occurred frequently after ICI initiation, with substantial variation by cancer type, comorbidities, and treatment regimen. These findings highlight the importance of cardiovascular risk assessment and monitoring to optimize outcomes in immuno-oncology.