Cardiac failure in patients treated with azacitidine, a pyrimidine analogue: Case reports and disproportionality analyses in Vigibase.

Abstract

AIMS:

Azacitidine (AZA), a pyrimidine analogue, is validated for high-risk myelodysplastic syndrome or low-blast acute myeloid leukaemia in unfit patients for more intensive treatment. This study assessed the putative link between cardiac failure (CF) and AZA exposure.

METHODS:

Cases of CF in patients treated with AZA were retrospectively collected and described from several centres of the Groupe Francophone des Myélodysplasies. A description analysis and a disproportionality analysis using Vigibase, the WHO Global Individual Case Safety Reports (ICSRs) database, were conducted on ICSRs by the Standardized MedDRA Queries (SMQ broad) cardiac failure and by preferred terms cardiac failure and cardiac failure acute. The reported odds ratio (ROR) and its 95% 2-sided confidence interval was computed by comparing the proportion of CF reports with the suspected drug (AZA) and the proportion of reports of the same adverse drug reaction with all other suspected drugs in the database during the same period.

RESULTS:

In the 4 case reports, all patients presented a cardiovascular history. In 1 patient, CF recurred after AZA re-challenge. The pharmacovigilance analysis in Vigibase retrieved 307 ICSRs of CF (SMQ) with AZA. Significant disproportionality signals associated with AZA were identified by using the SMQ cardiac failure (ROR 1.3) and the preferred terms cardiac failure (ROR 5.1) and cardiac failure acute (ROR 23.2).

CONCLUSION:

This study points to the potential role of AZA in the occurrence of CF. Cardiac evaluation before AZA initiation and regular monitoring of cardiac function during AZA treatment should be performed in patients with a history of cardiovascular disease.

• Authors: Justine Perino, Nathan Mottal, Yohann Bohbot, Vincent Servant, Aude Berroneau, Pierre Poustis, Pierre Fenaux, Kamel Laribi, Aude Charbonnier, Emilien Bilion, Claire Calmettes, Bernard Bégaud, Arnaud Pigneux, Noël Milpied, Ghada Miremont-Salamé, Hélène Théophile, Sophie Dimicoli-Salazar
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 86 Issue 5 Pg. 991-998 (05 2020) ISSN: 1365-2125 [Electronic] England
• PMID: 31912911 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2020 The British Pharmacological Society.

Chemical References

• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Pharmaceutical Preparations
• Azacitidine

Topics

• Adverse Drug Reaction Reporting Systems
• Aged
• Angiotensin Receptor Antagonists
• Angiotensin-Converting Enzyme Inhibitors
• Azacitidine (adverse effects)
• Databases, Factual
• Female
• Heart Failure (chemically induced, epidemiology)
• Hematopoietic Stem Cell Transplantation
• Humans
• Male
• Middle Aged
• Pharmaceutical Preparations
• Pharmacovigilance
• Retrospective Studies
• Stroke Volume
• Transplantation, Autologous
• Ventricular Function, Left