Management of Atrial Fibrillation in Patients on Ibrutinib: A Cleveland Clinic Experience.

Background Ibrutinib is a Bruton's tyrosine kinase inhibitor, which is United States Food and Drug Administration (FDA)-approved for chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström's macroglobulinemia. Ibrutinib is associated with atrial fibrillation and bleeding events. Our aim is to determine the management of prior atrial fibrillation when starting ibrutinib, as well as ibrutinib-induced atrial fibrillation. Our focus is on which rate and rhythm control strategies to use and decisions regarding the use of antiplatelet and anticoagulation agents. Materials and Methods We conducted a retrospective descriptive study of case records over a three-year period from February 2014 to February 2017. We reviewed 597 patient charts from the Cleveland Clinic database. Ibrutinib was started in 43 patients. Of those, 10 had atrial fibrillation prior to starting ibrutinib and four developed atrial fibrillation while on ibrutinib. Data was collected for demographic details, co-morbid conditions, CHA2 DS2 -VASc (congestive heart failure, hypertension, age, diabetes mellitus, prior stroke, transient ischemic attack or thromboembolism, vascular disease, age, and sex category) score, HAS-BLED (hypertension, abnormal renal and liver function, stroke, bleeding, labile INR, elderly, and drugs or alcohol) score, and drugs used for antiplatelet effects, for anticoagulation, and for rate and rhythm control. Outcomes for embolic and bleeding events were assessed. Results Of the 43 patients, 14 (32.5%) had or developed atrial fibrillation; 10 (23.26%) had prior atrial fibrillation, and four (9.30%) developed atrial fibrillation after starting ibrutinib. The majority were males (71.42%) and Caucasian (71.42%). The disease breakdown was chronic lymphocytic leukemia (42.86%), mantle cell lymphoma (50%), and Waldenström's macroglobulinemia (7.14%). The mean starting dose of ibrutinib in patients with prior atrial fibrillation was 569 mg and for patients who developed atrial fibrillation was 420 mg. In the 10 patients who had atrial fibrillation prior to ibrutinib, all 10  were on beta blockers, one was on diltiazem, three were on amiodarone, one was on flecainide, one was on digoxin, and one was on Tikosyn® (Pfizer, Inc., New York, NY). The ibrutinib dose was decreased/discontinued in two patients. In patients who developed atrial fibrillation after starting ibrutinib, three were on beta blockers, two on amiodarone, and one on Tikosyn. Ibrutinib was discontinued in one patient. In patients who had prior atrial fibrillation, three were on warfarin, one on enoxaparin, and two on apixaban. In three patients, aspirin and enoxaparin were discontinued. In patients who developed atrial fibrillation after starting ibrutinib, enoxaparin was given to two and apixaban to one. None of the patients had a stroke, transient ischemic attack (TIA), or bleeding events. Conclusions From our study, we concluded that ibrutinib can be safely given in the presence of atrial fibrillation, and when atrial fibrillation was induced, we further concluded that beta blockers were the preferred agents for rate control. Ibrutinib has many drug interactions with other rate and rhythm control agents; hence, their use was lower. When atrial fibrillation was uncontrolled, ibrutinib was temporarily held and then cautiously restarted. The decision to start or adjust anticoagulation depended on the bleeding and stroke risks as assessed by their physicians.