Atrial fibrillation as a complication of ibrutinib therapy: clinical features and challenges of management

Leuk Lymphoma. 2018 Feb;59(2):311-320. doi: 10.1080/10428194.2017.1339874. Epub 2017 Jun 20.

Abstract

Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor finding increasingly widespread use in non-Hodgkin lymphoma. Evidence of an increased risk of atrial fibrillation (AF) emerged in Phase III studies with a median incidence of approximately 6%. The mechanism remains unknown, but inhibition of a cardioprotective pathway has been proposed. Ibrutinib induces a platelet function defect, increasing the bleeding risk of anticoagulation for AF stroke prophylaxis. Multiple potential drug interactions are an added complication. In this review we examine the characteristics and management of the reported cases of AF with ibrutinib and where possible make recommendations. The evidence suggests dose reduction or temporary suspension of drug, are feasible alternative to discontinuation. The optimum choice of thromboprophylaxis has not been determined, but we propose the use of novel anticoagulants (NOACs) and avoidance of anti-platelet agents where possible. Further research and consensus guidelines are required.

Keywords: Atrial fibrillation; Waldenstrom macroglobulinemia; anti-coagulation; chronic lymphocytic leukemia; ibrutinib; mantle cell lymphoma.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Atrial Fibrillation / diagnosis*
  • Atrial Fibrillation / etiology*
  • Atrial Fibrillation / therapy*
  • Clinical Trials as Topic
  • Disease Management
  • Drug Interactions
  • Hemorrhage / diagnosis
  • Hemorrhage / etiology
  • Hemorrhage / prevention & control
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / complications
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy
  • Lymphoma, B-Cell / complications
  • Lymphoma, B-Cell / drug therapy
  • Piperidines
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazoles / adverse effects*
  • Pyrazoles / therapeutic use
  • Pyrimidines / adverse effects*
  • Pyrimidines / therapeutic use
  • Risk Factors
  • Severity of Illness Index

Substances

  • Anticoagulants
  • Antineoplastic Agents
  • Piperidines
  • Platelet Aggregation Inhibitors
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Adenine