Cardiovascular events of Bruton's tyrosine kinase inhibitors: A real-world study based on the United States Food and Drug Administration Adverse Event Reporting System database.
Br J Clin Pharmacol
; 90(9): 2166-2179, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38831641
ABSTRACT
AIMS:
Bruton's tyrosine kinase inhibitors (BTKIs), including first-generation ibrutinib, second-generation acalabrutinib and zanubrutinib, may be involved in the mechanisms of action related to adverse events (AEs) of the cardiovascular system. We aimed to characterize the cardiovascular AEs of BTKIs reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System, and to compare the cardiovascular risks of BTKIs.METHODS:
Across all indications of three FDA-approved BTKIs, primary suspect drugs were extracted over two periods from January 2013 to December 2022 (after the approval of the first BTKI), and from January 2020 to December 2022 (all three BTKIs on the market). Disproportionality was measured by reporting odds ratios (RORs) and information components. Additional analyses were performed without incorporating patients with underlying cardiovascular disease (CVD).RESULTS:
A total of 10 353 cases included the uses of ibrutinib, acalabrutinib and zanubrutinib. Ibrutinib was significantly associated with 47 cardiovascular AEs. Acalabrutinib was associated with new signals, including cardiac failure (ROR = 1.82 [1.13-2.93]), pulmonary oedema (ROR = 2.15 [1.19-3.88]), ventricular extrasystoles (ROR = 5.18 [2.15-12.44]), heart rate irregular (ROR = 3.05 [1.53-6.11]), angina pectoris (ROR = 3.18 [1.71-5.91]) and cardiotoxicity (ROR = 25.22 [17.14-37.10]). In addition, cardiovascular events had an earlier onset in acalabrutinib users. Zanubrutinib was only associated with atrial fibrillation. Acalabrutinib and zanubrutinib had lower ROR values than ibrutinib. The AE signals were generally consistent between the population receiving and not receiving CVD medications.CONCLUSIONS:
Potential cardiovascular risks identified in this study were not clearly noted on the label of marketed acalabrutinib. Caution should be paid to the cardiovascular risks of BTKIs having been or being developed.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
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Pirazóis
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Pirimidinas
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United States Food and Drug Administration
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Benzamidas
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Adenina
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Doenças Cardiovasculares
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Sistemas de Notificação de Reações Adversas a Medicamentos
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Inibidores de Proteínas Quinases
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Tirosina Quinase da Agamaglobulinemia
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Br J Clin Pharmacol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Reino Unido