ESC and CARDIOSOR scores as practical tools for cardiovascular risk stratification in patients with hepatocellular carcinoma (HCC) treated with atezolizumab/bevacizumab: data from a real-world multicentric study.

Background and Aims: The management of comorbidities has gained relevance in hepatocellular carcinoma (HCC) due to improved long-term survival. Bevacizumab, an anti-VEGF drug, increases the risk of major adverse cardiac events (MACE). Identifying at-risk patients is crucial since anti-VEGF-free therapeutic alternatives are now available. This study aimed to assess whether the European Society of Cardiology (ESC) antiangiogenic risk score and the CARDIOSOR score (Carballo-Folgoso, 2021) predict MACE in patients with HCC treated with atezolizumab/bevacizumab (AB). Methods: We retrospectively analyzed prospectively collected data from the multicentric Italian ARTE dataset, including patients treated with AB for unresectable HCC between June 2022 and July 2025. MACE occurrence was evaluated using a competing risk regression, considering non-cardiovascular death as a competing event. Results: Among 538 patients (median age 69.8 years), the prevalence of arterial hypertension and obesity was 56.3% and 18.4%, respectively. Moreover 7.6% had chronic coronary artery disease. Median follow-up was 22.4 months (95% CI 21.0-24.2 months) and median overall survival 19.7 months (95% CI 17.1-22.3). Twenty MACE (3.7%) occurred: 8 cerebrovascular accidents, 7 acute coronary syndromes, 3 strokes, and 2 heart failures. The cumulative incidence of MACE was 10.6%, 3.7%, 2.6%, and 0.7% in very high, high, medium and low risk groups according to the ESC score (sHR 3.80, 95% CI 1.52–9.45, p=0.004). Patients with a high-risk CARDIOSOR score also had an increased risk of MACE (sHR 2.70, 95% CI 1.08–6.74, p=0.03). Conclusion: These findings suggest that the ESC and CARDIOSOR scores could be used to stratify the risk of MACE in patients receiving AB. These tools might inform clinicians and provide relevant information when evaluating the choice of the first line regimen.