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. 2025 Apr 7;37(1):120.
doi: 10.1007/s40520-025-03025-4.

Safety of direct oral anticoagulants reversal agents in older patients: an analysis of individual case safety reports of adverse drug reaction from VigiBase®

Giada Crescioli  1   2 , Niccolò Lombardi  3   4 , Elena Arzenton  5 , Nicoletta Luxi  5 , Stefano Fumagalli  6 , Roberto Bonaiuti  3   4 , Costanza Cacini  3   4 , Guido Mannaioni  3   7 , Gianluca Trifirò  5 , Ugo Moretti  5 , Alfredo Vannacci  3   4
Affiliations

Safety of direct oral anticoagulants reversal agents in older patients: an analysis of individual case safety reports of adverse drug reaction from VigiBase®

Giada Crescioli et al. Aging Clin Exp Res. .

Abstract

Background: Real-world data on adverse drug reactions (ADRs) associated with idarucizumab and andexanet alfa are limited.

Aim: This study aimed to assess the frequency, the characteristics and clinical and demographic factors associated with ADRs related to their use.

Methods: This is a retrospective analysis of ADR reports collected in Vigibase® until May 31, 2023. Multivariable logistic regression estimated reporting odds ratios (RORs) for serious ADRs, death, and thromboembolic events according to demographical and clinical covariates.

Results: A total of 1095 Individual Case Safety Reports (ICSRs) reporting idarucizumab (72%) or andexanet alfa (28%) as suspected/interacting agents were collected. Most of the subjects were males (44.5%), with a median age of 78 years, and exposed to only one suspected/interacting medication (73.6%). ADRs were defined as serious in 88.6% of cases, with a total of 614 (56.1%) fatal cases. Compared to patients without concomitant medications, probability of serious ADRs and death were both higher in those receiving ≥ 5 concomitant medications in the idarucizumab subgroup (ROR 4.04 and 1.66, respectively) and in those receiving 1-4 concomitant medications in the andexanet alfa subgroup (ROR 5.66 and 4.80, respectively). Moreover, the probability of thromboembolic events was significantly lower for subjects aged > 75 years (ROR for 75-84 years 0.55; ROR for ≥ 85 years 0.50).

Discussion: In real-world, ADRs associated with idarucizumab and andexanet alfa use are generally serious, resulting in death in a high percentage of subjects.

Conclusion: Clinicians should pay particular attention when managing individuals needing these drugs, especially if vulnerable and requiring polytherapy.

Keywords: Adverse drug reaction; Andexanet Alfa; Idarucizumab; Observational study; Pharmacovigilance..

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Conflict of interest statement

Declarations. Statement of human and animal rights: This article does not contain any study with humans and animals performed by any of the authors. Informed consent: Due to the retrospective nature of the present study and data anonymization, patient’s consent to participate was not required. UMC statement: VigiBase, the WHO global database of ICSRs is the source of our information. The information comes from a variety of sources, and the probability that the suspected adverse event is drug-related is not the same in all cases; the information does not represent the opinion of the UMC or WHO. Competing interests: Over the last 3 years, Professor Gianluca Trifirò has participated in advisory boards and seminars funded by Sanofi, MSD, Eli Lilly, Sobi, Celgene, Daichii Sankyo, Novo Nordisk, Gilead, and Amgen. He is the scientific coordinator of the academic spin-off “INSPIRE srl”, which has received funding from several pharmaceutical companies (i.e., PTC Pharmaceuticals, Kiowa Kirin, Shonogi, Shire, Novo Nordisk, and Daichii Sankyo) for conducting observational studies. Additionally, he is currently a consultant for Viatris in a legal case concerning an adverse reaction to sertraline. None of these listed activities are related to the topic of the article. All other authors have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Country of origin of ICSRs with idarucizumab or andexanet alfa as suspected/interacting drug
Fig. 2
Fig. 2
Co-reported suspected/interacting drugs in ICSRs with idarucizumab and andexanet alfa as suspected/interacting drug
See this image and copyright information in PMC

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