Cardiac side effects of bruton tyrosine kinase (BTK) inhibitors

Leuk Lymphoma. 2018 Jul;59(7):1554-1564. doi: 10.1080/10428194.2017.1375110. Epub 2017 Sep 13.

Abstract

The development of bruton tyrosine kinase inhibitors (BTKi) has been a significant advancement in the treatment of chronic lymphocytic leukemia and related B-cell malignancies. As experience in using ibrutinib increased, the first drug to be licensed in its class, atrial fibrillation (AF) emerged as an important side effect. The intersection between BTKi therapy for B-cell malignancies and AF represents a complex area of management with scant evidence for guidance. Consideration needs to be taken regarding the interplay of increased bleeding risk versus thromboembolic complications of AF, drug interactions between ibrutinib and anticoagulants and antiarrhythmic agents, and the potential for other, as yet seldom reported cardiac side effects. This review describes the current knowledge regarding BTKi and potential pathophysiologic mechanisms of AF and discusses the management of BTKi-associated AF. Finally, a review of the second generation BTKi is provided and gaps in knowledge in this evolving field are highlighted.

Keywords: Bruton kinase inhibitor; atrial fibrillation; ibrutinib.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors*
  • Agammaglobulinaemia Tyrosine Kinase / metabolism
  • Anticoagulants / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / etiology
  • Atrial Fibrillation / physiopathology
  • Atrial Fibrillation / therapy
  • Cardiotoxicity / diagnosis
  • Cardiotoxicity / etiology*
  • Cardiotoxicity / metabolism
  • Cardiotoxicity / therapy
  • Clinical Trials as Topic
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / complications
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Piperidines
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use
  • Signal Transduction
  • Treatment Outcome

Substances

  • Anticoagulants
  • Antineoplastic Agents
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Agammaglobulinaemia Tyrosine Kinase
  • Adenine