Cardiovascular toxicities following the use of tyrosine kinase inhibitors in Hepatocellular Cancer Patients: A Retrospective, Pharmacovigilance Study

Aims: With the extensive use of tyrosine kinases inhibitors(TKIs) in hepatocellular cancer, cardiac adverse events(AEs) emerged in recent years. This study explored the cardiac AEs of TKIs through the Food and Drug Administration’s Adverse Event Reporting System (FAERS). Methods: Disproportionality analysis and Bayesian analysis were utilized for data mining of the suspected cardiac AEs of TKIs, based on FAERS data from January 2004 to December 2021. Results: A total of 4708 cardiac AEs reports of sorafenib, regorafenib, lenvatinib and cabozantinib were identifed. Among them, 17 cardiac AEs signals were detected in regorafenib, 15 cardiac AEs signals were detected in lenvatinib, 57 cardiac AEs signals were detected in sorafenib while 27 cardiac AEs signals were detected in cabozantinib. Hypertension accounts for the most reported cardiac AE. Lenvatinib appears to induce cardiac failure with the highest signals strength [ROR=7.7(3.46,17.17)]. Acute myocardial infarction were detected in lenvatinib [ROR=7.91(5.64,11.09)] and sorafenib[ROR=2.22(1.74, 2.84)]. Acute coronary syndrome were detected in lenvatinib[ROR=11.57(6.84, 19.58)] and sorafenib [ROR=2.81(1.87,4.24)]. Atrial fibrillation were detected in sorafenib [ROR=1.82(1.55,2.14)] and regorafenib [ROR=1.36(1.03,1.81)]. Meanwhile, aortic dissection were detected in sorafenib [ROR=5.08(3.31,7.8)] and regorafenib [ROR=3.39(1.52,7.56)]. Most patients developed hypertension and cardiac failure within 30 days after TKIs treatment. Patients taking lenvatinib developed acute coronary syndrome increased in the periods of 180 days(64.29%) . Conclusion: Analysis of FAERS provides more precise profile on the characteristics of cardiac AEs after different TKI regimens. Distinct monitoring and appropriate management are needed in the care of the TKIs recipients.