Predictors of atrial fibrillation in ibrutinib-treated CLL patients: a prospective study

J Hematol Oncol. 2018 Jun 11;11(1):79. doi: 10.1186/s13045-018-0626-0.


Background: Ibrutinib is an oral irreversible inhibitor of Bruton's tyrosine kinase, indicated for the treatment of chronic lymphocytic leukaemia. The drug is generally well tolerated; however, not infrequent side effects are reported, with the major two being bleeding and ibrutinib-related atrial fibrillation. Atrial fibrillation pathogenesis in this setting is not completely clear, and no prospective studies have evaluated the impact of previous cardiologic history and baseline characteristics.

Methods: We prospectively performed cardiologic assessment in 43 CLL patients before starting ibrutinib therapy. Cardiologic workup included comorbidity collection and electrocardiographic and echocardiographic baseline evaluation.

Results: After a median observation of 8 months, seven patients developed atrial fibrillation (16.3%). Cases developing atrial fibrillation were all elderly males (p = 0.04), and mostly with a history of previous arterial hypertension (p = 0.009). Atrial fibrillation occurrence also correlated with the presence of one or more pre-existent cardiologic comorbidities (p = 0.03), with a higher atrial fibrillation risk score (calculated with comorbidities and cardiologic risk factor evaluation p < 0.001), and with higher left atrial diameter (p = 0.02) and area (p = 0.03) by echocardiography. The occurrence of atrial fibrillation was managed after an integrated cardio-oncologic evaluation: anticoagulation was started in 4 (57.1%) patients and beta-blockers or amiodarone in 5 (71.4%). One patient underwent electric cardioversion and another patient pacemaker positioning to normalise heart rate in order to continue ibrutinib.

Conclusion: Our data show that echocardiography is a highly informative and reproducible tool that should be included in pre-treatment workup for patients who are candidates for ibrutinib therapy.

Keywords: Atrial fibrillation; Cardio-oncology; Chronic lymphocytic leukaemia; Ibrutinib.

Publication types

  • Letter

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors
  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / chemically induced
  • Atrial Fibrillation / etiology*
  • Echocardiography / methods
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / complications
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Male
  • Middle Aged
  • Prospective Studies
  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases
  • Pyrazoles / adverse effects*
  • Pyrazoles / therapeutic use*
  • Pyrimidines / adverse effects*
  • Pyrimidines / therapeutic use*
  • Reproducibility of Results


  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase