Author information

¹Department of Medical and Surgical Sciences, University of Bologna, 40138, Bologna, Italy. bernardo.stefanini@studio.unibo.it.

²Department of Medical and Surgical Sciences, University of Bologna, 40138, Bologna, Italy.

³Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.

⁴Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy.

⁵Liver Unit, Department of Transplantation, Cardarelli Hospital, Naples, Italy.

⁶Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy.

⁷Gastroenterology Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

⁸Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy.

⁹Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padova, Padua, Italy.

¹⁰Medical Oncology and Hematology Unit, Humanitas Clinical and Research Center, Rozzano (Milan), Italy.

¹¹Department 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.

¹²Department of Internal Medicine, Ospedale Per Gli Infermi Di Faenza, Faenza, Italy.

¹³Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.

^#Contributed equally.

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.