French nationwide, population-based study of comparative atrial fibrillation risk across BTK inhibitors in B-cell malignancies

Bruton’s tyrosine kinase inhibitors (BTKi) are widely used in B-cell malignancies. Ibrutinib is associated with atrial fibrillation (AF). A nationwide new-user population study in France investigated AF risk with ibrutinib, acalabrutinib, zanubrutinib, and venetoclax. Using the French national health insurance database (2015-2024), the authors identified 26 393 patients starting one of these medications, excluding those with prior AF or non-overlapping BTKi indications. The primary outcome was AF requiring hospitalization. One-year incidence of hospitalized AF was highest with ibrutinib (2.3%) versus acalabrutinib (0.9%), zanubrutinib (0.7%), and venetoclax (0.5%). Ibrutinib was associated with a significantly higher AF risk versus acalabrutinib (HR 3.03; 95% CI 1.84-5.00), zanubrutinib (7.58; 2.05-28.06), and venetoclax (9.04; 5.81-14.04). No significant differences in AF risk were observed between second-generation BTKi and venetoclax. The authors conclude that ibrutinib was associated with a substantially higher risk of hospitalized AF than second-generation BTKi, supporting closer cardiac monitoring in ibrutinib-treated patients (graphical abstract).