Cardiovascular Events of Bruton’s Tyrosine Kinase Inhibitors: A
Real-World Study Based on the FDA Adverse Events Reporting System
(FAERS) Database
Abstract
Abstract Aims Bruton’s tyrosine kinase inhibitors (BTKIs), including
first-generation ibrutinib, second-generation acalabrutinib, and
zanubrutinib may have certain mechanisms of action (MOAs) related to
adverse effects (AEs) on the cardiovascular system. We aimed to evaluate
the cardiac AEs of BTKIs reported to the U.S. Food and Drug
Administration Adverse Event Reporting System (FAERS) and to compare the
differences in cardiovascular toxicity of ibrutinib, acalabrutinib, and
zanubrutinib. Methods Only primary suspect drugs from the FAERS database
were extracted from January 2013 to December 2022 across all indications
of FDA-approved BTKIs. Disproportionality was measured by reporting odds
ratios (RORs) and information components (ICs). An additional
disproportionality analysis was also performed from January 2020 to
December 2022. Results A total of 10,353 cases involving ibrutinib,
acalabrutinib and zanubrutinib were included. Ibrutinib was
significantly associated with the incidence of cerebrovascular
accidents, myocardial infarction and other thrombotic events.
Acalabrutinib was associated with new signals, including cardiac
failure, ventricular extrasystoles, pulmonary edema and angina pectoris,
and hypertension and myocardial infarction were found in additional
analyses. Furthermore, acalabrutinib was characterized by a much earlier
onset of cardiovascular events. Only atrial fibrillation was associated
with zanubrutinib use. Acalabrutinib and zanubrutinib had lower ROR
values for cardiac AEs, and fewer signals for these two drugs compared
with ibrutinib. Conclusion This study indicated that new AEs were not
clearly noted on the label for acalabrutinib. It is suggested that the
cardiovascular risks of BTKIs remain a concern and worth attention as
next-generation BTKIs are discovered and developed.