Cumulative incidence, risk factors, and management of atrial fibrillation in patients receiving ibrutinib

Atrialfibrillation (AF) hasbeen reported inup to 16% of patients taking ibrutinib. Data regarding the management of AF in this patient population are limited, and stroke prevention poses a challenge because of increased risk of bleeding with ibrutinib treatment. Our study sought to describe the incidence of AF in adult patients treated with ibrutinib for a hematologic malignancy, assessmanagement strategies, evaluate stroke andbleeding outcomes, and identify risk factors for occurrence. Of 582 patients treated with ibrutinib, 76 developed AF. With a median follow-up of 32 months, the estimated cumulative incidence at 6 months, 1 year, and 2 years was 5.9% (95% confidence interval [CI]: 4.2-8.0), 7.5% (95% CI: 5.5-9.9), and 10.3% (95% CI: 8.0-13.0), respectively. Median time to onset of AF was 7.6 months. History of AF and Framingham Heart Study (FHS) AF risk score were found to be significant risk factors for development of AF. Most patients were treated with rate control-only strategies (61.8%), and concomitant aspirin or anticoagulant therapy with ibrutinib was used in 52.6% and 28.9% of patients, respectively. One patient on aspirin developed symptoms consistent with stroke. Nine major bleedswere noted in 7 patients, and 34 clinically relevant nonmajor bleedswere noted in 24 patients. Twenty-one bleeds (4 major bleeds) occurred in 18 patients on aspirin, and 10 bleeds (all clinically relevant nonmajor bleeds) occurred in 6 patients with anticoagulant therapy. These results provide risk factor assessment, impact of management strategies, and outcomes of patients with AF on ibrutinib and serve as basis for formal guidelines.