Abstract
ABSTRACT
Background & Aims
The management of comorbidities has become increasingly relevant in unresectable hepatocellular carcinoma (uHCC) as immunotherapy prolongs survival. Atezolizumab plus bevacizumab (AB) is a standard first‐line option, but bevacizumab carries a risk of cardiovascular toxicities. Data on cardiovascular risk stratification in patients with cirrhosis remain limited. Identifying patients at increased cardiovascular risk is therefore clinically important, particularly given the availability of bevacizumab‐free alternatives.
Methods
We retrospectively analysed prospectively collected data from the multicenter Italian ARTE database, including patients with uHCC treated with first‐line AB between June 2022 and July 2025. Traditional major adverse cardiovascular events (tMACE) were defined as acute coronary syndromes, heart failure, cerebrovascular events, or peripheral ischemia, while an extended composite (eMACE) additionally included venous thromboembolism and immune‐related myocarditis. Cardiovascular risk was stratified using the European Society of Cardiology (ESC) Cardio‐Oncology classification and the CARDIOSOR score. Competing‐risk analyses were performed considering treatment discontinuation as a competing event.
Results
This study included 538 patients (median age 69.8 years). During follow‐up, 20 patients (3.7%) experienced tMACE, and 30 (5.6%) experienced eMACE. Patients assigned to the very high‐risk category by ESC criteria and those with a high‐risk CARDIOSOR score had a significantly increased risk of tMACE and eMACE. Both scores demonstrated a moderate ability to stratify cardiovascular risk (Harrell's c‐index 0.68 for ESC and 0.59 for CARDIOSOR).
Conclusions
Cardiovascular adverse events were uncommon overall, but their incidence was not negligible in patients in high‐risk subgroups. Risk scores may help identify vulnerable subgroups and support patient‐tailored treatment strategies, including consideration of bevacizumab‐free regimens in selected cases.
Trial Registration
Multicenter ARTE database (NCT06806579)