Determinants of Atrial Fibrillation Development among Patients undergoing Ibrutinib Therapy.

Within the last decade, the use of ibrutinib, a first-generation, non-selective, irreversible Burton's tyrosine kinase inhibitor for the treatment of hematological malignancies has proven highly effective in improving patient outcomes. Ibrutinib has been associated with an increase in atrial fibrillation (AF). The predisposing factors are thought to be pre-existing cardiovascular risk factors, but these have not been directly evaluated. We conducted a nested case-control study, recruiting consecutive ibrutinib treated subjects to evaluate cardiovascular risk factors associated with the development of AF in patients diagnosed with hematological B-cell malignancies. Of the 189 patients treated with ibrutinib and without AF at baseline, 54 (29%) developed AF. Cardiovascular risk factors associated with AF development were, older age, prior hypertension (HTN), history of heart failure (HF) and congenital heart disease. A patient with HF at baseline had a 1, 2, 6, and 12 month cumulative hazard of AF of 40%, 48%, 64%, and 71%, respectively. Patients with prior HTN without HF at baseline had a 1, 2, 6, and 12 month cumulative hazard of AF of 5%, 10%, 23%, and 31%, respectively while on ibrutinib therapy. The relationship between ibrutinib, cardiovascular comorbidities, and AF is through pre-existing cardiovascular disease. An individualized, multidisciplinary approach involving cardiologists should be considered when initiating ibrutinib, particularly when there is a history of HTN, HF or congenital heart disease. In such patients, there should be close cardiovascular monitoring and prompt intervention when AF develops to improve patient outcomes.