Author + information
- Received March 15, 2018
- Revision received June 6, 2018
- Accepted June 6, 2018
- Published online December 17, 2018.
- Sarju Ganatra, MDa,b,∗ (, )
- Ajay Sharma, MDb,
- Sachin Shah, MDb,
- Ghulam M. Chaudhry, MDb,
- David T. Martin, MDb,
- Tomas G. Neilan, MD, MPHc,
- Syed Saad Mahmood, MDd,
- Ana Barac, MD, PhDe,
- John D. Groarke, MD, MPHf,g,
- Salim S. Hayek, MDh,
- Saurbha Dani, MDi,
- David Venesy, MDb,
- Richard Patten, MDb and
- Anju Nohria, MDf,g
- aCardio-Oncology Program, Division of Cardiovascular Medicine, Lahey Hospital and Medical Center, Burlington, Massachusetts
- bDivision of Cardiovascular Medicine, Department of Medicine, Lahey Hospital and Medical Center, Burlington, Massachusetts
- cCardio-Oncology Program, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts
- dDivision of Cardiovascular Medicine, New York Presbyterian Hospital/Weill Cornell Medical Center, New York, New York
- eCardio-Oncology Program, Division of Cardiology, Medstar Washington Hospital Center, Washington, DC
- fDivision of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- gCardio-Oncology Program, Dana-Farber Cancer Institute, Boston, Massachusetts
- hDivision of Cardiology, Emory University, Atlanta, Georgia
- iDivision of Cardiovascular Medicine, Eastern Maine Medical Center, Bangor, Maine
- ↵∗Address for correspondence:
Dr. Sarju Ganatra, Cardio-Oncology Program, Division of Cardiovascular Medicine, Lahey Hospital and Medical Center, 41 Mall Road, Burlington, Massachusetts 01805.
Ibrutinib, a novel and potent Bruton tyrosine kinase inhibitor, is an effective and well-tolerated treatment for a variety of B-cell lymphomas. However, its use is associated with an increased incidence of atrial fibrillation (AF), ranging from 4% to 16%. We reviewed the original clinical trials that led to the approval of ibrutinib, as well as several other prospective and retrospective studies, to better appreciate the incidence of ibrutinib-associated AF. Based on 16 studies included in our analysis, the incidence of ibrutinib-associated AF was 5.77 per 100 person-years, which is much higher than rates previously reported with ibrutinib and compared with the general adult population. New onset AF in cancer patients is associated with a significantly higher risk of heart failure and thromboembolism, even after adjusting for known risk factors. In addition, ibrutinib poses unique challenges due to its interactions with many medications that are commonly used to manage AF. Ibrutinib also inhibits platelet activation and decisions regarding anticoagulation have to be carefully weighed against this increased risk of bleeding. Ibrutinib’s interaction with calcium channel blockers, digoxin, amiodarone, and direct oral anticoagulants can result in either ibrutinib or other drug-related toxicity and careful selection and dose adjustment may be needed. Ibrutinib-associated AF can be a therapy-limiting side effect and physicians should be familiar with the special management considerations imposed by this agent. We review the potential mechanisms and incidence of ibrutinib-associated AF and propose an algorithm for its management.
Dr. Martin serves on the Steering Committee for Abbott; consults for Biotronik; and has received honoraria from Abbott and Biotronik. Dr. Neilan is a member of the scientific advisory board with Takeda. Dr. Mahmood has received consulting fees from Medicare, OMR Globus, Alpha Detail, and Opinion Research Team. Dr. Nohria has received research support from Amgen; is a consultant with and Takeda Oncology; and has received honoraria from Takeda Oncology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received March 15, 2018.
- Revision received June 6, 2018.
- Accepted June 6, 2018.
- 2018 American College of Cardiology Foundation