Prediction of cardiovascular risk in patients with hepatocellular carcinoma receiving anti-angiogenic drugs: lessons from sorafenib

Bernardo Stefanini; Francesco Tovoli; Franco Trevisani; Mariarosaria Marseglia; Giovan Giuseppe Di Costanzo; Giuseppe Cabibbo; Rodolfo Sacco; Filippo Pellizzaro; Tiziana Pressiani; Rusi Chen; Francesca Romana Ponziani; Francesco Giuseppe Foschi; Giulia Magini; Alessandro Granito; Fabio Piscaglia; Italian Liver Cancer (ITA.LI.CA) group

doi:10.1007/s11739-024-03578-8

Prediction of cardiovascular risk in patients with hepatocellular carcinoma receiving anti-angiogenic drugs: lessons from sorafenib

Intern Emerg Med. 2024 Mar 29. doi: 10.1007/s11739-024-03578-8. Online ahead of print.

Authors

Bernardo Stefanini^#¹, Francesco Tovoli^#^{2

3}, Franco Trevisani^{2

4}, Mariarosaria Marseglia³, Giovan Giuseppe Di Costanzo⁵, Giuseppe Cabibbo⁶, Rodolfo Sacco^{7

8}, Filippo Pellizzaro⁹, Tiziana Pressiani¹⁰, Rusi Chen², Francesca Romana Ponziani¹¹, Francesco Giuseppe Foschi¹², Giulia Magini¹³, Alessandro Granito^{2

3}, Fabio Piscaglia^{2

3}; Italian Liver Cancer (ITA.LI.CA) group

Affiliations

¹ Department of Medical and Surgical Sciences, University of Bologna, 40138, Bologna, Italy. bernardo.stefanini@studio.unibo.it.
² Department of Medical and Surgical Sciences, University of Bologna, 40138, Bologna, Italy.
³ Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.
⁴ Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.
⁵ Liver Unit, Department of Transplantation, Cardarelli Hospital, Naples, Italy.
⁶ Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy.
⁷ Gastroenterology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
⁸ Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy.
⁹ Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padova, Padua, Italy.
¹⁰ Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center, Rozzano (Milan), Italy.
¹¹ Department of Specialty and Transplant Medicine, Internal Medicine and Gastroenterology, Gastroenterology, Hepatology and Transplant Unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Roma- Università Cattolica del Sacro Cuore, Rome, Italy.
¹² Department of Internal Medicine, Ospedale Per Gli Infermi Di Faenza, Faenza, Italy.
¹³ Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.

^# Contributed equally.

PMID: 38551755
DOI: 10.1007/s11739-024-03578-8

Abstract

Antiangiogenics are associated with an increased risk of major adverse cardiac and cerebrovascular events (MACE). The identification of at-risk subjects is relevant in the case of hepatocellular carcinoma (HCC), for which anti-angiogenic TKIs and bevacizumab are used in first and subsequent lines of therapy, to select alternative drugs for patients with excessive risk. We verified the ability to predict MACE in sorafenib-treated patients of the 2022 European Society of Cardiology (ESC-2022) score for anti-angiogenics and the recently proposed CARDIOSOR score. A retrospective analysis was conducted of prospectively collected data of the ARPES and ITA.LI.CA databases. All patients received sorafenib for unresectable HCC from 2008 to 2018. Baseline information to calculate the ESC-2022 and CARDIOSOR scores and registration of evolutive events (including MACE) were available for all patients. The predictive ability of both scores was verified using competing risk regressions and tests for goodness of fit. This study included 843 patients (median follow-up 11.3 months). Thirty-four (4.0%) patients presented a MACE. The four-tier ESC-2022 classification showed a progressive risk increase for every class (cumulative risk 1.7%, 2.7%, 4.3%, and 15.0% in the low, medium, high, and high-risk tiers, respectively). The dichotomous CARDIOSOR scale identified a high-risk group with a fourfold increased risk of MACE (sHR 4.66, p = 0.010; cumulative risk 3.8% and 16.4%). ESC-2022 showed a better goodness of fit compared to the CARDIOSOR score [C-index 0.671 (0.583-0.758) vs 0.562 (0.501-0.634), p = 0.021], but this gap was eliminated using the linear version of CARDIOSOR. Both the ESC-2022 and CARDIOSOR scores discriminated patients at increased risk for MACE. The use of these scores in clinical practice should be encouraged, since therapeutic measures can mitigate the cardiovascular risk.

Keywords: Antiangiogenics; Bevacizumab; Cardiovascular events; Heart failure; Hepatocellular carcinoma; Myocardial infarction; Sorafenib; Stroke.