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Arrhythmias and sudden death
Original research article
High incidence of atrial fibrillation in patients treated with ibrutinib
  1. Florian Baptiste1,
  2. Jennifer Cautela1,
  3. Yan Ancedy2,
  4. Noémie Resseguier3,
  5. Thérèse Aurran4,
  6. Laure Farnault5,
  7. Marion Escudier1,
  8. Chloé Ammar1,
  9. Mélanie Gaubert1,
  10. Charles Dolladille6,
  11. Jeremie Barraud1,
  12. Michael Peyrol1,
  13. Ariel Cohen2,
  14. Franck Paganelli1,
  15. Joachim Alexandre6,
  16. Stephane Ederhy2 and
  17. Franck Thuny1
  1. 1 Department of Cardiology, Unit of Heart Failure and Valvular Heart Diseases, Mediterranean University Cardio-Oncology Center (MEDI-CO Center), Hôpital Nord, Aix-Marseille I University, Marseille, France
  2. 2 Université Pierre et Marie Curie, Paris, France
  3. 3 Biostatistic and Public Healt Department, Hopital de la Timone, Marseille, France
  4. 4 Department of Haematology, Institut Paoli-Calmettes, Marseille, France
  5. 5 Department of Haematology, Aix-Marseille I University, Marseille, France
  6. 6 PICARO Cardio-oncology Program, Department of Pharmacology, CHRU de Caen, Caen, France
  1. Correspondence to Dr Franck Thuny; franck.thuny{at}gmail.com

Abstract

Objective Atrial fibrillation (AF) is one of the most common side effects of ibrutinib, a drug that has dramatically improved the prognosis of chronic B-cell malignancies such as chronic lymphocytic leukaemia (CLL). The true incidence of ibrutinib-related AF (IRAF) is not well known and its therapeutic management poses unique challenges especially due to the inherent risk of bleeding. We aimed to determine the incidence and predictors of IRAF, and to analyse its management and outcome.

Methods A standardised monitoring was applied at two cardio-oncology clinics in consecutive patients referred before and during ibrutinib therapy. The primary endpoint was the incidence of IRAF. The excess of AF incidence with ibrutinib was studied by comparing the incidence of IRAF with the expected incidence of AF in general population and in patients with CLL not exposed to ibrutinib.

Results 53 patients were included. The incidence of IRAF was 38% at 2 years and the risk was 15-fold higher than the AF risk in both the general population and patients with CLL not exposed to ibrutinib (p<0.0001). The majority of cases occurred in asymptomatic patients within the first 6 months. Left atrial volume index ≥40 mL/m2 at treatment initiation identified patients at high risk of developing IRAF. No major bleeding events occurred in patients on ibrutinib, although the majority of patients with IRAF were treated with anticoagulants.

Conclusions This cardio-oncology study showed that the risk of IRAF was much higher than previously reported. The majority of cases occurred in asymptomatic patients justifying close monitoring.

  • atrial fibrillation
  • cardio-oncology
  • cardiotoxicity
  • ibrutinib

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/openhrt-2019-001049

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    Footnotes

    • Contributors Substantial contributions to the conception and design of the work: FT, JC and SE. Acquisition, analysis and interpretation of data for the work: FB, YA, CA, ME, MG, JB, MP, AC, FP, LB, ML, NR, TA, LF, JA and CD. Drafting the work and revising it critically for important intellectual content: FT, JC, FB, SE, LF, TA, JA and CD. Final approval of the version to be published: FB, JC, YA, NR, LF, TA, CA, ME, MG, JB, MP, ML, LB, AC, FP, SE, FT, JA and CD.

    • Funding This study was supported by La Ligue Contre le Cancer and Assistance Publique – Hôpitaux de Marseille.

    • Competing interests JC received received modest consultant and lecture fees from MSD, Janssen, Merck, Novartis, Astra-Zeneca. FT received grants from Fédération Francaise de Cardiologie, Ministère français de la Santé, Fondation Coeur et Recherche, Ligue contre le Cancer, Assistance Publique – Hôpitaux de Marseille, Vifor Pharma. FT exercised an expert activity with Institut Nationale du Cancer. FT received personal fees for lectures and speakers bureaus from Abbott, Novartis, Amgen, Janssen-Cilag, Merck Sharp and Dohme, Bristol-Myers Squibb, Pfizer, Roche, Vifor Pharma, Sanofi, Astra-Zeneca. FT received non-financial support for travel and lunch paid from Abbott, Novartis, Amgen, Janssen-Cilag, Merck Sharp and Dohme, Bristol-Myers Squibb, Pfizer, Roche, Vifor Pharma, Sanofi, Astra-Zeneca, Servier, Sorin, Boston Scientific, Actelion, Bayer, Biotronik, Boehinger Ingelheim, The Medecines Compagny, Orion Pharma, Correvio, Daiichi Sankyo, St Jude Medical, Lilly, Zoll Medical, LivaNova, Medtronic, Sorin, Philips, Genzyme, Icomed, Leo Pharma, Mylan Medical, Preciphar, Resmed. AC received modest consultant and lecture fees from Astra-Zeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, and Sanofi-Aventis.Stephane Ederhy received modest consultant and lecture fees from Lilly, Daiichy-Sankyo, Celgene, Pfizer, Esperare, Bristol-Myers Squibb, Janssen, Philips Healthcare, Bayer, Novartis, Amgen, Ipsen.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement All data relevant to the study are included in the article or uploaded as supplementary information.