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

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.