Cardiovascular toxicities following the use of tyrosine kinase inhibitors in hepatocellular cancer patients: a retrospective, pharmacovigilance study

ABSTRACT

Background

Cardiac adverse events (AEs) are common in tyrosine kinase inhibitors(TKIs). 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 identified. 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 was detected in lenvatinib [ROR = 7.91 (5.64,11.09)] and sorafenib [ROR = 2.22 (1.74, 2.84)]. Acute coronary syndrome was detected in lenvatinib [ROR = 11.57 (6.84, 19.58)] and sorafenib [ROR = 2.81 (1.87,4.24)]. Atrial fibrillation was detected in sorafenib [ROR = 1.82 (1.55,2.14)] and regorafenib [ROR = 1.36 (1.03,1.81)]. Meanwhile, aortic dissections 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 of initiating TKI treatments. Patients taking lenvatinib had an increased incidence of developing acute coronary syndrome after 180 days of treatment.

Conclusion

Analysis of FAERS data provides a precise profile on the characteristics of cardiac AEs associated with different TKI regimens. Distinct monitoring and appropriate management are needed in the care of TKI recipients.

KEYWORDS:

• Cardiac adverse events
• data mining
• hepatocellular cancer
• non-proportional analysis
• tyrosine kinases inhibitors

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

Concept and design the work: HW-Peng, JF-Hu. Acquisition, analysis, or interpretation of data: X Lai, Q Wan. Management and checking of all data: SF-Jiao and XC-Sun. Drafting the article: X Lai and Q Wan. All authors critically reviewed the manuscript and interpreted the results. The final manuscript was read, checked, and approved by all authors.

Acknowledgments

The authors are very grateful to all staffs of the institute of clinical pharmacology at the First Affiliated Hospital of Nanchang University.

Data availability statement

Publicly available datasets were analyzed in this study. This data can be found at https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was funded by the National Natural Sciences Foundation Committee (NSFC) [NO:81860035], Jiangxi Provincial Key Research and Development Plan [NO:20203BBGL73210], Jiangxi Provincial Academic Leaders Training Plan [NO: 20204BCJ23024] and Clinical Pharmaceutical Research Fund of the China International Medical Exchange Foundation [Z-2021-46-2101].