Cardiovascular events in patients with hepatocellular carcinoma treated with atezolizumab bevacizumab: a real-world cardiooncology study

Abstract

Atezolizumab plus bevacizumab is the current standard first-line treatment for patients with advanced hepatocellular carcinoma (HCC). While cardiovascular toxicity is a recognized concern, real-world data on the incidence, spectrum, and predictors of cardiovascular events in patients treated with this combination remain limited.

Purpose

The aim of this study was to assess the incidence and predictors of cardiovascular events in a real-world cohort of patients with HCC treated with atezolizumab–bevacizumab.

Methods

We performed a propsective observational study including 70 consecutive patients with HCC receiving atezolizumab–bevacizumab and referred for cardio-oncology evaluation. Cardiovascular events were defined as a composite endpoint including all-cause death, new-onset or worsening arterial hypertension (including hypertensive crisis), ischemic events, arrhythmias, thromboembolic events, heart failure, and cardiotoxicity. Baseline clinical characteristics, inflammatory parameters, and cardiac biomarkers were collected. Univariable logistic regression was used to identify predictors of cardiovascular events. Median follow-up was 9 months.

Results

During follow-up, 25 patients (36%) experienced at least one cardiovascular event. The composite endpoint was mainly driven by all-cause death (n = 14, 24%) and new-onset or worsening arterial hypertension (n = 4, 10%), whereas other cardiovascular events were less frequent [ischemic events (n = 3), arrhythmias (n = 5), thromboembolic events (n = 2), and heart failure (n = 1)]. Notably, no cases of myocarditis were observed. Patients with cardiovascular events were older (75 [68–80] vs 69 [58–76] years, p = 0.015), were more frequently classified as very high risk according to the HFA–ICOS score compared with those without events (32% vs 13%) and exhibited higher inflammatory markers, including white blood cell (p = 0.049) and neutrophil counts (p = 0.044). High-sensitivity troponin and NT-proBNP levels were also significantly higher in patients with events (p = 0.017 and p = 0.007, respectively).

At univariable analysis, age was associated with cardiovascular events (OR 1.07 per year, 95% CI 1.01–1.14; p = 0.023). NT-proBNP (OR 2.56, 95% CI 1.27–6.05; p = 0.016) and log-transformed troponin (OR 7.59, 95% CI 1.56–57.78; p = 0.025) emerged as significant predictors of events, whereas traditional cardiovascular risk factors were not.

Conclusions

In a real-world cohort of patients with HCC treated with atezolizumab–bevacizumab, cardiovascular events occurred in approximately one third of patients over a 9-month follow-up. Older age, increased inflammatory burden, and elevated baseline cardiac biomarkers were associated with a higher risk of cardiovascular events. These findings highlight the importance of careful cardiovascular monitoring and biomarker-based risk stratification in patients receiving atezolizumab–bevacizumab in routine clinical practice.