Pharmacovigilance analysis of cardiac risks associated with Bruton tyrosine kinase inhibitors.

BACKGROUND: Bruton tyrosine kinase inhibitors (BTKIs) can be associated with several cardiac risks. RESEARCH DESIGN AND METHODS: The study was conducted based on records from a large spontaneous reporting database, the Food and Drug Administration Adverse Event Reporting System, for cardiac events reported for several BTKI agents. Reporting odds ratio and information components based on statistical shrinkage transformation were utilized to measure disproportionality. RESULTS: The final number of records for BTKI-related cardiac events was 10 320. Death or life-threatening events occurred in 17.63% of all associated cardiac records. Significant reporting was captured between BTKI (total/specific) and cardiac events, with the strongest association for ibrutinib. A total of 47 positive signals were evacuated for ibrutinib, with atrial fibrillation being the most commonly reported one. Concomitantly, cardiac failure, congestive, cardiac disorder, arrhythmia, pericardial effusion, and atrial flutter were also noticed for relatively stronger signal and disproportionality. Atrial fibrillation was over-reported in the three groups (ibrutinib, acalabrutinib, and zanubrutinib), and acalabrutinib had statistically significant lower reporting compared with ibrutinib. CONCLUSIONS: Receiving ibrutinib, acalabrutinib, or zanubrutinib might increase the chance of cardiac complications, with ibrutinib posing the highest risk. The type of cardiotoxicity involved in ibrutinib was highly variable.