Cardiovascular Toxicities Associated With Ibrutinib
| Autor: | Marie Bretagne, Douglas B. Johnson, Christian Funck-Brentano, Ali Manouchehri, Dan M. Roden, Nishitha Reddy, Joe-Elie Salem, Jennifer R. Brown, Bénédicte Lebrun-Vignes, Javid Moslehi, Tao Yang, John D. Groarke |
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| Přispěvatelé: | Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS) |
| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty cardio-oncology Databases Factual [SDV.CAN]Life Sciences [q-bio]/Cancer 030204 cardiovascular system & hematology Culprit Pharmacovigilance 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Piperidines [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ibrutinib Internal medicine medicine Adverse Drug Reaction Reporting Systems Humans atrial fibrillation 030212 general & internal medicine Mortality Adverse effect Aged Retrospective Studies Aged 80 and over business.industry Adenine Atrial fibrillation Odds ratio medicine.disease Confidence interval 3. Good health Clinical trial Pyrimidines chemistry Cardiovascular Diseases cardiology Ibrutinib oncology cardiac failure [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology Pyrazoles Female [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ventricular tachycardia Cardiology and Cardiovascular Medicine business |
| Zdroj: | Journal of the American College of Cardiology Journal of the American College of Cardiology, Elsevier, 2019, 74 (13), pp.1667-1678. ⟨10.1016/j.jacc.2019.07.056⟩ |
| ISSN: | 0735-1097 |
| DOI: | 10.1016/j.jacc.2019.07.056 |
| Popis: | International audience; BACKGROUND: Ibrutinib has revolutionized treatment for several B-cell malignancies. However, a recent clinical trial where ibrutinib was used in a front-line setting showed increased mortality during treatment compared with conventional chemotherapy. Cardiovascular toxicities were suspected as the culprit but not directly assessed in the study.OBJECTIVES: The purpose of this study was to identify and characterize cardiovascular adverse drug reactions (CV-ADR) associated with ibrutinib.METHODS: This study utilized VigiBase (International pharmacovigilance database) and performed a disproportionality analysis using reporting odds ratios (ROR) and information component (IC) to determine whether CV-ADR and CV-ADR deaths were associated with ibrutinib. IC compares observed and expected values to find associations between drugs and adverse drug reactions using disproportionate Bayesian-reporting; IC025 (lower end of the IC 95% credibility interval) >0 is significant.RESULTS: This study identified 303 ibrutinib-associated cardiovascular deaths. Ibrutinib was associated with higher reporting of supraventricular arrhythmias (SVAs) (ROR: 23.1; 95% confidence interval: 21.6 to 24.7; p < 0.0001; IC025: 3.97), central nervous system (CNS) hemorrhagic events (ROR: 3.7; 95% confidence interval: 3.4 to 4.1; p < 0.0001; IC025: 1.63), heart failure (ROR: 3.5; 95% confidence interval: 3.1 to 3.8; p < 0.0001; IC025: 1.46), ventricular arrhythmias (ROR: 4.7; 95% confidence interval: 3.7 to 5.9; p < 0.0001; IC025: 0.96), conduction disorders (ROR: 3.5; 95% confidence interval: 2.7 to 4.6; p < 0.0001; IC025: 0.76), CNS ischemic events (ROR: 2.2; 95% confidence interval: 2.0 to 2.5; p < 0.0001; IC025: 0.73), and hypertension (ROR: 1.7; 95% confidence interval: 1.5 to 1.9; p < 0.0001; IC025: 0.4). CV-ADR often occurred early after ibrutinib administration. Importantly, CV-ADR were associated with fatalities that ranged from ∼10% (SVAs and ventricular arrhythmias) to ∼20% (CNS events, heart failure, and conduction disorders). Ibrutinib-associated SVA portends poor prognosis when CNS events occur concomitantly, with 28.8% deaths (15 of 52 cases).CONCLUSIONS: Severe and occasionally fatal cardiac events occur in patients exposed to ibrutinib. These events should be considered in patient care and in clinical trial designs. (Evaluation of Reporting of Cardio-vascular Adverse Events With Antineoplastic and Immunomodulating Agents [EROCA]; NCT03530215). |
| Databáze: | OpenAIRE |
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