High-grade heart block associated with ibrutinib therapy

Vartanov, Alexander R.; Lampson, Benjamin L.; Jacobsen, Eric; Alyea, Edwin P.; Moslehi, Javid; Brown, Jennifer R.

doi:10.1016/j.hrcr.2021.03.013

Cited by 4 publications

(5 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conduction disorders signal over-reporting is concordant with a previous pharmacovigilance study in VigiBase evaluating the cardiovascular safety of ibrutinib (Salem et al, 2019). In a recent case-series of ibrutinib-induced high-grade heart block, 14 out of 18 cases of high degree heart block occurred within 13 months of ibrutinib initiation (Vartanov et al, 2021). All patients required pacemaker placement, and most resumed ibrutinib without recurrence of conduction disorders.…”

Section: Potential Safety Signalssupporting

confidence: 81%

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database

et al. 2021

View full text Add to dashboard Cite

As ibrutinib has become a standard of care in B-cell malignancies in monotherapy or in combination with other agents, definition of its safety profile appears essential. The aim of this study was to further characterize the safety profile of ibrutinib through the identification of potential safety signals in a large-scale pharmacovigilance database. All serious individual case safety reports (ICSRs) in patients aged ≥18 years involving ibrutinib suspected in the occurrence of serious adverse drug reactions or drug interacting from November 13th, 2013 to December 31st, 2020 were extracted from VigiBase, the World Health Organization global safety database. Disproportionality reporting was assessed using the information component (IC) and the proportional reporting ratio (PRR), with all other anticancer drugs used as the reference group. To mitigate the confounding of age, two subgroups were considered: patients aged<75 years and ≥75 years. A signal of disproportionate reporting (SDR) was defined if both IC and PRR were significant. A total of 16,196 ICSRs were included. The median age of patients was 72.9 years, 42.6% of ICSRs concerned patients aged ≥75 years, and 64.2% male patients. More than half (56.2%) of ICSRs resulted in hospitalization or prolonged hospitalization. Among 713 SDRs, 36 potential safety signals emerged in ibrutinib-treated patients, mainly ischemic heart diseases, pericarditis, uveitis, retinal disorders and fractures. All potential safety signals having arisen in this analysis may support patient care and monitoring of ongoing clinical trials. However, owing to the mandatory limitations of this study, our results need further confirmation using population-based studies.

show abstract

Section: Potential Safety Signalssupporting

confidence: 81%

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Based on previous studies, patients on ibrutinib therapy have a well-known risk of developing atrial fibrillation. Incidence of atrial fibrillation can be as high as 5-16% as shown earlier in this article [3][4][5][6][7][8]. However, newer case series and studies are showing a possible relation between ibrutinib therapy and conduction disease.…”

Section: Discussionmentioning

confidence: 50%

“…Our study here shows two patients at our facility who presented with advanced conduction abnormalities requiring permanent pacemaker placement. These cases along with the previous others described in the study by Vartanov et al show a new adverse effect to monitoring while patients are on ibrutinib therapy [3]. No clear mechanism has been established for the development of these advanced conduction abnormalities.…”

Section: Discussionmentioning

confidence: 70%

“…In this report, we specifically focus on ibrutinib therapy causing cardiac conduction disorders, specifically high-degree heart block and sinus arrest. Per the study by Vartanov et al there have been at least 18 cases with reported high-degree heart blocks [3]. Here we present two unique cases from our institution.…”

Section: Introductionmentioning

confidence: 57%

“…Patients who develop atrial fibrillation on ibrutinib therapy are managed medically with rate control medications and initiation of anticoagulation, while keeping in mind that ibrutinib therapy has an increased bleeding risk, however therapy can continue for these patients. Other studies demonstrate ventricular arrhythmias arising with patients on ibrutinib therapy and in some cas-es, leading to cardiac death [3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Advanced Cardiac Conduction Abnormalities in Patients on Ibrutinib Therapy

Patel,

Robin,

Robin

2024

SciBase Cardiol

View full text Add to dashboard Cite

Background: Bruton tyrosine kinase inhibitors, such as ibrutinib, are medications that are actively used for Chronic Lymphocytic Leukemia (CLL) and several lymphomas. They work by inhibiting Bruton’s tyrosine kinase therefore affecting B cell proliferation. Ibrutinib itself is associated with multiple cardiotoxicities including atrial fibrillation, ventricular arrhythmias, heart failure, and bleeding. There are well-established studies that show the incidence of atrial fibrillation with ibrutinib therapy. However, only a few reports show an association between ibrutinib therapy and advanced heart block. Case presentation: We present two unique cases of patients who presented to the emergency room with syncope while being on ibrutinib therapy for CLL. At presentation, the patients were found to have conduction abnormalities seen on their EKG that included complete heart block in one patient and sick sinus syndrome in the other. Ultimately, each patient was treated with a pacemaker, ibrutinib therapy was discontinued, and they were started on alternative therapy for their CLL. Discussion: No clear mechanism has been established for how ibrutinib therapy causes these conduction abnormalities. This case series proposes a possible mechanism of advanced conduction abnormalities that is caused by ibrutinib therapy that is associated with the NOTCH gene. We propose that the downregulation of the NOTCH gene may prevent cardiac myocyte remodeling and therefore can cause conduction abnormalities as seen in our patients along with others that presented with advanced heart block with ibrutinib therapy.

show abstract

Ibrutinib

2022

Reactions Weekly

View full text Add to dashboard Cite

High-grade heart block associated with ibrutinib therapy

Cited by 4 publications

References 15 publications

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database

Advanced Cardiac Conduction Abnormalities in Patients on Ibrutinib Therapy

Ibrutinib

Contact Info

Product

Resources

About