Predictors of ibrutinib-associated atrial fibrillation: 5-year follow-up of a prospective study

Abstract

Ibrutinib-associated atrial fibrillation (IRAF) emerged among the adverse events of major interests in ibrutinib-treated patients as real-world studies showed a higher incidence compared to clinical trials. We prospectively analyzed predictors of IRAF in 43 single-center consecutive patients affected by chronic lymphocytic leukemia that started therapy with ibrutinib between 2015 and 2017. Key secondary endpoints were to describe the management of IRAF and survival outcomes. During a median follow-up period of 52 months, we registered 45 CV events, with a total of 23 AF events in 13 patients (CI 30.0% (95% CI: 16.5–43.9)). Pre-existent cardiovascular risk factors, in particular hypertension, a previous history of AF and a high Shanafelt risk score emerged as predictors of IRAF. Baseline echocardiographic evaluation of left atrial (LA) dimensions confirmed to predict IRAF occurrence and cut-off values were identified in our cohort: 32 mm for LA diameter and 18 cm2 for LA area. No difference in progression free survival and overall survival emerged in patients experiencing IRAF. Following AF, anticoagulation was started in all eligible patients, and cardioactive therapy was accordingly modified. Echocardiography represents a highly reproducible and widespread tool to be included in the work-up of ibrutinib candidates; the identification of IRAF predictors represents a useful guide to clinical practice.