Cardiological adverse events in hepatocellular carcinoma patients receiving immunotherapy: Influence of comorbidities and clinical outcomes

INTRODUCTION: Immunotherapy-based combinations have revolutionized the first-line treatment for advanced hepatocellular carcinoma (HCC), improving overall survival (OS). However, these therapies are associated with adverse events (AEs), particularly cardiological complications and major adverse cardiovascular events (MACE), which may adversely affect outcomes. The influence of comorbid conditions such as arterial hypertension (AHT) and type 2 diabetes mellitus (T2DM) on the incidence and prognosis of cardiological AEs in HCC patients remains understudied. METHODS: This retrospective study included 109 HCC patients treated with atezolizumab-bevacizumab, tremelimumab-durvalumab, or durvalumab as first-line therapy at two Spanish medical centers from 2017-2023. Patients were stratified by comorbidities, AE incidence, and cardiological risk (CARDIOSOR scale). The primary endpoints were the incidence of treatment-modifying AEs and MACE, and their association with survival. RESULTS: Among the cohort, 50.5 % experienced AEs of special interest (AESI), with 34 % considered immune-related (irAE). MACE occurred in 7.3 % of patients, including myocarditis (3.7 %). The CARDIOSOR scale identified a higher risk of MACE in patients with AHT, T2DM, or both (OR: 5.07, p = 0.034). Early cardiological AEs were independently associated with worse OS (HR: 3.38, p = 0.04). Patients with both AHT and T2DM exhibited higher rates of MACE (16.7 %) and treatment discontinuation (25.9 %). The CARDIOSOR scale effectively stratified patients into high-risk groups, correlating with increased MACE rates and poor survival outcomes. CONCLUSIONS: Comorbid conditions, particularly AHT and T2DM, amplify the risk of MACE and influence treatment discontinuation. The CARDIOSOR scale is a valuable tool for personalized risk assessment, guiding tailored therapeutic strategies. Integrating cardiovascular risk management into HCC care is crucial for optimizing both oncological and cardiovascular outcomes.