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Analysis of fatal adverse drug events recorded in several Italian emergency departments (the MEREAFaPS study)

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Abstract

Fatal Adverse Events (FADEs) are a major public health problem, and some FADEs could be preventable. The aim of the present study is to describe the frequency, the drugs involved and the preventability in the FADEs collected through the MEREAFaPS Study between 2012 and 2018. All cases including the outcome “death” have been examined. We excluded cases with vaccine-related ADEs, overdose or suicide, and ADEs occurred during the hospitalisation. Two trained assessors evaluated all cases fulfilling the inclusion criteria. ADEs’ preventability was evaluated applying the Schumock and Thornton algorithm. During the study period, we observed 429 cases of death, 92 of which were excluded. The remaining 337 cases involved 187 women and 150 men, with a mean age of 79 and of 77 years, respectively. For each report, the suspected drugs and concomitant ones were 1.26 and 4.20, respectively. Anticoagulants and antiplatelet agents account for more than 40% of FADE cases and the most frequent reactions are haemorrhages (37.5%). The 25% of the FADEs were preventable. This study confirms that FADEs are still a relevant clinical occurrence, and are often caused by widely used old drugs associated with adverse events. The death of one in four patients was preventable. Further efforts should be done to improve the appropriateness of the therapy, especially in older patients who are treated with anticoagulants.

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Acknowledgements

Members of the MEREAFaPS Study group who provided patient data for this study: Maria Luisa Aiezza (Naples), Alessandra Bettiol (Florence), Daria Bettoni (Brescia), Corrado Blandizzi (Pisa), Roberto Bonaiuti (Florence), Valentina Borsi (Florence), Annalisa Capuano (Naples), Errica Cecchi (Prato), Irma Convertino (Pisa), Giada Crescioli (Florence), Martina Del Lungo (Florence), Cristina Di Mauro (Naples), Gabriella Farina (Milan), Sara Ferraro (Pisa), Annamaria Fucile (Naples), Elena Galfrascoli (Milan), Elisabetta Geninatti (Turin), Linda Giovannetti (Florence), Luca Leonardi (Pisa), Rosa Liccardo (Naples), Niccolò Lombardi (Florence), Anna Marra (Ferrara), Eleonora Marrazzo (Turin), Giovanna Monina (Gallarate), Alessandro Mugelli (Florence), Silvia Pagani (Vimercate), Maria Parrilli (Florence), Concetta Rafaniello (Naples), Francesco Rossi (Naples), Marco Rossi (Siena), Stefania Rostan (Naples), Marco Ruocco (Vimercate), Marita Sironi (Vimercate), Giulia Spada (Vimercate), Liberata Sportiello (Naples), Marco Tuccori (Pisa), Alfredo Vannacci (Florence), Mauro Venegoni (Vimercate), Giuditta Violetta Vighi (Vimercate), Giuseppe Danilo Vighi (Vimercate).

Funding

Mereafaps Study was funded by a research grant from the AIFA (the Italian Medicines Agency), Rome, Italy, Fondi Regionali per la Farmacovigilanza. Giunta Regionale della Lombardia, Delibera n° 2112 del 11/07/2014. The funder of the study had no role in the collection, analysis and interpretation of data, nor in the writing of the report, nor in the decision to submit the article for publication.

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Author notes

  1. S. Pagani, N. Lombardi and G. Crescioli authors contributed equally.

Authors and Affiliations

  1. Department of Medicine, ASST Vimercate, Via Santi Cosma e Damiano 10, 20871, Vimercate, MB, Italy

    Silvia Pagani, Paola Andreetta, Mauro Venegoni & Giuseppe Danilo Vighi

  2. Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy

    Niccolò Lombardi, Giada Crescioli & Alfredo Vannacci

  3. Hospital Pharmacy, ASST Vimercate, Vimercate, Italy

    Giuditta Violetta Vighi, Giulia Spada & Isabella Romoli

  4. Section of Pharmacology “L. Donatelli”, Department of Experimental Medicine, Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, University of Campania “Luigi Vanvitelli”, Naples, Italy

    Annalisa Capuano

  5. Piedmont Regional Centre for Pharmacovigilance, Turin, Italy

    Eleonora Marrazzo

  6. Hospital Pharmacy, “Sant’Anna” University Hospital, Ferrara, Italy

    Anna Marra

  7. Lombardy Regional Centre for Pharmacovigilance, Milan, Italy

    Olivia Leoni

  8. Department of Health Sciences, University of Verona, Verona, Italy

    Mauro Venegoni

Authors
  1. Silvia Pagani
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  2. Niccolò Lombardi
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  3. Giada Crescioli
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  4. Giuditta Violetta Vighi
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  5. Giulia Spada
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Consortia

The MEREAFaPS Study group

  • Alessandra Bettiol
  • , Daria Bettoni
  • , Corrado Blandizzi
  • , Roberto Bonaiuti
  • , Valentina Borsi
  • , Annalisa Capuano
  • , Errica Cecchi
  • , Irma Convertino
  • , Giada Crescioli
  • , Martina Del Lungo
  • , Cristina Di Mauro
  • , Gabriella Farina
  • , Sara Ferraro
  • , Annamaria Fucile
  • , Elena Galfrascoli
  • , Elisabetta Geninatti
  • , Linda Giovannetti
  • , Luca Leonardi
  • , Rosa Liccardo
  • , Niccolò Lombardi
  • , Anna Marra
  • , Eleonora Marrazzo
  • , Giovanna Monina
  • , Alessandro Mugelli
  • , Silvia Pagani
  • , Maria Parrilli
  • , Concetta Rafaniello
  • , Francesco Rossi
  • , Marco Rossi
  • , Stefania Rostan
  • , Marco Ruocco
  • , Marita Sironi
  • , Giulia Spada
  • , Liberata Sportiello
  • , Marco Tuccori
  • , Alfredo Vannacci
  • , Mauro Venegoni
  • , Giuditta Violetta Vighi
  •  & Giuseppe Danilo Vighi

Contributions

Study design was contributed by P, L, C and V, with assistance from the rest of the authors. P took the lead in data analysis, assisted by A, L and C. Data interpretation was performed by P, L, C, V and V, with assistance from the other authors. The manuscript was written primarily by P, L, C and V, with assistance from the other authors, and revised by C, V and V. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Silvia Pagani.

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Conflicts of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethics approval

The MEREAFaPS Study was approved in 2006 by the local institutional ethics committee of the coordinating centre, Niguarda Ca’ Granda Hospital, according to the legal requirements concerning observational studies [20].

Informed consent

Due to the retrospective nature of the present study and data anonymization, patient’s consent to participate was not required.

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Pagani, S., Lombardi, N., Crescioli, G. et al. Analysis of fatal adverse drug events recorded in several Italian emergency departments (the MEREAFaPS study). Intern Emerg Med 16, 741–748 (2021). https://doi.org/10.1007/s11739-020-02521-x

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