ArticleCirculation2020
Ibrutinib-Mediated Atrial Fibrillation Attributable to Inhibition of C-Terminal Src Kinase.
Article in Circulation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03530215 (Evaluation of Reporting of Cardio-vascular Adverse Events With Antineoplastic and Immunomodulating Agents), which is not on this map. Cited by 146 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Evaluation of Reporting of Cardio-vascular Adverse Events With Antineoplastic and Immunomodulating Agents (EROCA)
Who cites it
146 citing papers in PubMed, 6 syntheses or guidelines pooled it, 227 citations in OpenAlex.
- Cardiac safety profiles of first-generation vs second-generation BTK inhibitors: a meta-analysis.The oncologist · 2026Pooled it
- Real‑life diagnostic and therapeutic approach to CLL/SLL in tuscany: the 2025 consensus.Clinical and experimental medicine · 2026Guideline
- Cardiovascular Challenges in Chronic Lymphocytic Leukemia (CLL) Patients Undergoing Bruton Tyrosine Kinase (BTK) Inhibitor Therapy.European journal of haematology · 2026Pooled it
- Evaluating the use of rodents as in vitro, in vivo and ex vivo experimental models for the assessment of tyrosine kinase inhibitor-induced cardiotoxicity: a systematic review.Archives of toxicology · 2025Pooled it
- Guideline
- 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.Journal of the American College of Cardiology · 2024Guideline
- Safety, pharmacokinetics, and pharmacodynamics of sofnobrutinib, a novel non-covalent BTK inhibitor, in healthy subjects: First-in-human phase I study.Clinical and translational science · 2024Trial
- Trial
- Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Mechanisms of resistance to BTK inhibitors in B cell malignancies and emerging targeted strategies.Molecular therapy. Oncology · 2026Review
- Cardiovascular Toxicity of BTK Inhibitors: A Patient-Centered Framework for Risk Stratification and Management.Journal of clinical medicine · 2026Review
- Comparative atrial fibrillation risk across Bruton's tyrosine kinase inhibitors in B-cell malignancies: A nationwide population-based study.British journal of haematology · 2026Article
- Cardiotoxicity of Targeted Therapies in Hematologic Malignancies: From Molecular Mechanisms to Clinical Management.Current treatment options in oncology · 2026Review
- Non-receptor tyrosine kinase signaling pathways and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Cardiovascular Toxicity of BTKi in Chronic B-Cell Malignancies.Reviews in cardiovascular medicine · 2026Review
- A Comprehensive Review of the Role of Zanubrutinib for Patients with Chronic Lymphocytic Leukemia.Oncology and therapy · 2026Review
- Atrial fibrillation associated with tyrosine kinase inhibitors: A case-control study of real-world pharmacovigilance data.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Sudden death and asymptomatic arrhythmia in chronic lymphocytic leukemia patients treated with ibrutinib.Heart rhythm · 2026Article
- Transthoracic Echocardiography as a Tool for Early Detection of Atrial Fibrillation in Patients Receiving Ibrutinib.Life (Basel, Switzerland) · 2026Article
86 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
18 authors at 9 institutions in 4 countries.
Funding
Abstract
backgroundIbrutinib is a Bruton tyrosine kinase inhibitor with remarkable efficacy against B-cell cancers. Ibrutinib also increases the risk of atrial fibrillation (AF), which remains poorly understood.
methodsWe performed electrophysiology studies on mice treated with ibrutinib to assess inducibility of AF. Chemoproteomic analysis of cardiac lysates identified candidate ibrutinib targets, which were further evaluated in genetic mouse models and additional pharmacological experiments. The pharmacovigilance database, VigiBase, was queried to determine whether drug inhibition of an identified candidate kinase was associated with increased reporting of AF.
resultsWe demonstrate that treatment of mice with ibrutinib for 4 weeks results in inducible AF, left atrial enlargement, myocardial fibrosis, and inflammation. This effect was reproduced in mice lacking Bruton tyrosine kinase, but not in mice treated with 4 weeks of acalabrutinib, a more specific Bruton tyrosine kinase inhibitor, demonstrating that AF is an off-target side effect. Chemoproteomic profiling identified a short list of candidate kinases that was narrowed by additional experimentation leaving CSK (C-terminal Src kinase) as the strongest candidate for ibrutinib-induced AF. Cardiac-specific Csk knockout in mice led to increased AF, left atrial enlargement, fibrosis, and inflammation, phenocopying ibrutinib treatment. Disproportionality analyses in VigiBase confirmed increased reporting of AF associated with kinase inhibitors blocking Csk versus non-Csk inhibitors, with a reporting odds ratio of 8.0 (95% CI, 7.3-8.7;
conclusionsThese data identify Csk inhibition as the mechanism through which ibrutinib leads to AF. Registration: URL: https://ww.clinicaltrials.gov; Unique identifier: NCT03530215.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.