Identification of anticancer drugs associated with atrial fibrillation: analysis of the WHO pharmacovigilance database

Alexandre, Jonas; Salem, Joe‐Elie; Moslehi, Javid; Sassier, Marion; Ropert, Camille; Cautela, Jennifer; Thuny, Franck; Éderhy, Stéphane; Damaj, Ghandi; Vilque, Jean-Pierre; Plane, Anne-Flore; Legallois, Damien; Champ‐Rigot, Laure; Milliez, Paul; Funck‐Brentano, Christian; Dolladille, Charles

doi:10.1093/ehjcvp/pvaa037

Cited by 58 publications

(48 citation statements)

References 31 publications

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“…5 VigiBase was already described and used to identify and characterize ADRs associated with anticancer drugs, including immune checkpoint inhibitors. [6][7][8][9][10] In the present study, we used the deduplicated VigiBase (supplementary-methods) to perform a retrospective, disproportionality analysis of reports from January, 1,2015 (year of first CAR-T report in VigiBase) up to March 1, 2020. Accuracy of VigiMatch, a probabilistic record-matching algorithm used for the detection and exclusion of duplicates in VigiBase, has been described elsewhere.…”

Section: Data Source and Study Designmentioning

confidence: 99%

Chimeric antigen receptor T‐cells safety: A pharmacovigilance and meta‐analysis study

et al. 2021

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Chimeric-antigen-receptor T cells directed against CD19 (CAR-T) are emerging hematological therapeutics with scarce data on its overall safety profile spectrum. To determine the clinical features and incidence of adverse-drug reactions (ADR) associated with CAR-T. This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase and meta-analysis of data from CAR-T trials and cohorts in the literature was also performed through March, 2020. The primary objective was to identify ADR associated with approved CAR-T (axicabtagene-ciloleucel; tisagenlecleucel). We conducted a Bayesian disproportionate analysis with the 95% lower credibilityinterval of information component (IC 025 , significance > 0). We also performed a systematic-review and meta-analysis of CAR-T trials and cohorts in the literature to evaluate ADR incidence. Nine ADR classes were associated with CAR-T: Cytokine release syndrome (CRS, n = 1378, IC 025 = 4.24), neurological disorders (n = 963, IC 025 = 2.42), hematological disorders (n = 532, IC 025 = 3.32), infections (n = 287, IC 025 = 2.38), cardiovascular disorders (n = 256, IC 025 = 2.81), pulmonary disorders (n = 186, IC 025 = 3.80), reno-metabolic disorders (n = 123, IC 025 = 1.89), hemophagocytic-lymphohistiocytosis (n = 36, IC 025 = 5.01) and hepatic disorders (n = 32, IC 025 = 2.49). ADR-related fatalities accounted for 99/1783 (5.5%) of the reports and 262/1783 (14.7%) for all-cause mortality. These ADR-related fatalities were associated with hemophagocytic-lymphohistiocytosis, cerebral vascular disorder, infections, and respiratory failure. In meta-analyses, the most frequent any-grade ADRs were CRS, hematological disorders, and neurological disorders. Fatal ADR were most found with neurological disorders, CRS, and infections. Note, CAR-T infusion may be associated with severe ADR mainly following the week of administration, though rarely fatal. Infections, hemophagocytic-lymphohistiocytosis and end organ failures including neurological or lung involvements require scrutiny.

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Section: Data Source and Study Designmentioning

confidence: 99%

Chimeric antigen receptor T‐cells safety: A pharmacovigilance and meta‐analysis study

et al. 2021

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“…Alexandre et al used the World Health Organization (WHO) individual case safety report database, vigibase, to identify the correlation between anticancer drugs and AF. As the results showed, 11,757 of 2,124,646 AF cases were associated with 176 anticancer drugs, and nilotinib accounted for 241 cases (2%) (45).…”

Section: Nilotinibmentioning

confidence: 96%

“…Ibrutinib is an independent risk factor for the development of atrial arrhythmias, with an incidence of AF of more than 10-15% (42)(43)(44). Based on Alexandre's paper, ibrutinib is the most frequent anticancer drug to cause AF (45). In addition to straightforward arrhythmias, other potential effects of ibrutinib on ECG are little known.…”

Section: Ibrutinibmentioning

confidence: 99%

Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies

Cheng

Yang

Liu

et al. 2021

Front. Cardiovasc. Med.

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With the development of anti-tumor drugs, tyrosine kinase inhibitors (TKIs) are an indispensable part of targeted therapy. They can be superior to traditional chemotherapeutic drugs in selectivity, safety, and efficacy. However, they have been found to be associated with serious adverse effects in use, such as myocardial infarction, fluid retention, hypertension, and rash. Although TKIs induced arrhythmia with a lower incidence than other cardiovascular diseases, much clinical evidence indicated that adequate attention and management should be provided to patients. This review focuses on QT interval prolongation and atrial fibrillation (AF) which are conveniently monitored in clinical practice. We collected data about TKIs, and analyzed the molecule mechanism, discussed the actual clinical evidence and drug-drug interaction, and provided countermeasures to QT interval prolongation and AF. We also pooled data to show that both QT prolongation and AF are related to their multi-target effects. Furthermore, more than 30 TKIs were approved by the FDA, but most of the novel drugs had a small sample size in the preclinical trial and risk/benefit assessments were not perfect, which led to a suspension after listing, like nilotinib. Similarly, vandetanib exhibits the most significant QT prolongation and ibrutinib exhibits the highest incidence in AF, but does not receive enough attention during treatment.

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“…The association of chemotherapy and RT is an important aspect to be considered in the potential development of cardiac disease in cancer patients and plays a key role as a risk factor. Cardiovascular diseases are gaining more attention as undesirable effects of anticancer drugs (Alexandre et al 2020). Up to 30% of patients receiving chemotherapy may develop a cardiac side effect during their lifetime (Mihalcea et al 2017).…”

Section: Cardiotoxicity Induced By Chemotherapymentioning

confidence: 99%

Preliminary pre-clinical studies on the side effects of breast cancer treatment

Salata

deAlmeida

Ferreira-Machado

et al. 2021

International Journal of Radiation Biology

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Purpose: Technological advancement in the treatment of cancer together with early detection and diagnosis have considerably improved the survival of breast cancer patients. On the other hand, the potential of patients developing side effects from cancer treatment are not negligible. Despite the progress that has been made in terms of early diagnosis, therapy, and survival, including improvements in the chemotherapeutic agents, radiation and molecular targeted therapies, cardiotoxicity of cancer therapy is still cause for concern. Radiation therapy for breast cancer is associated with increased risk of heart disease and myocardial infarction. Furthermore, the association of radiation therapy to chemotherapy is an important aspect to be considered in the development of cardiac disease, as this could play an additional role as a risk factor. Besides the heart effect, other side effects can be observed in the bone, ovary, uteri, and other organs. This paper aims to review the recent literature to present the current understanding of side effects associated with breast cancer treatment. The focus is on recent preclinical studies that have assessed potential changes in different organs that may be injured after breast cancer treatment, both due to both radiation and chemotherapy agents. Conclusion: Radiation-induced heart disease is one important side effect that must be considered during the treatment planning and patient follow-up. The cardiac damage can be potentialized when chemotherapy is associated to radiotherapy, and the literature findings indicate that heart fibrosis plays an important role at the radio-chemotherapy induced cardiac damage. Literature findings also showed important side effects at the bone, that can lead to ospeoporosis, due to the decrease of calcium, after radio or chemotherapy treatments. This decrease could be explained by the ovarian failure observed at rats after chemotherapy treatment. It is of great importance to acknowledge the complications originating from the treatment, so that new strategies can be developed. In this way, it will be possible to minimize side effects and improve the patients' quality of life.

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Identification of anticancer drugs associated with atrial fibrillation: analysis of the WHO pharmacovigilance database

Cited by 58 publications

References 31 publications

Chimeric antigen receptor T‐cells safety: A pharmacovigilance and meta‐analysis study

Chimeric antigen receptor T‐cells safety: A pharmacovigilance and meta‐analysis study

Tyrosine Kinase Inhibitors-Induced Arrhythmias: From Molecular Mechanisms, Pharmacokinetics to Therapeutic Strategies

Preliminary pre-clinical studies on the side effects of breast cancer treatment

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