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Cardiovascular adverse events-related to GnRH agonists and GnRH antagonists: analysis of real-life data from Eudra-Vigilance and Food and Drug Administration databases entries

Prostate Cancer and Prostatic Diseases volume 26, pages 765–771 (2023)Cite this article

Subjects

Abstract

Introduction and objectives

GnRH agonists and GnRH antagonists are two of the mainstays of hormonal therapy (HT) for prostate cancer (PCa). These drugs are at increased risk of cardiovascular (CV) adverse events (AEs). Aim of our study was to compare real-life data on AEs associated with GnRH agonists and GnRH antagonists based on Eudra-Vigilance (EV) and Food and Drug Administration (FDA) reported AEs.

Materials and methods

EV and FDA databases were queried and the number of CV adverse events (AEs) for degarelix, buserelin, goserelin, leuprorelin, triptorelin until September 2021 were recorded. Specific CV AEs were recorded and data were analyzed per age and severity. pooled relative risk (PRR) was used to compare data between drugs.

Results

CV events were reported in 315/5128 (6%) for Degarelix, in 55/628 for Buserelin (9%), in 843/12,145 (7%) for Goserelin, in 3395/71,160 (5%) for Leuprorelin and in 214/4969 (5%) for Triptorelin. In terms of specific CV disorders, Degarelix presented lower risk of hypertension (PRR 0.60 (95% CI 0.37–0.98), p = 0.04), of myocardial infarction (PRR 0.05 (95% CI 0.01–0.39), p < 0.01) and thrombosis (PRR 0.14 (0.02–1.07), p = 0.06) when compared to GnRH agonists. Overall, younger patients (<65 years) presented a very low risk of CV AEs. Side effects were classified as serious in 90–96% of the cases. Fatal AEs were 5–20% over the CV AEs and 0.2–1% over the total AEs.

Conclusions

Real-life data are consistent with registry studies regarding side effects related to HT. Real-life data suggest GnRH agonists are associated with higher CV AEs when compared to GnRH antagonists. Clinicians should consider these data when prescribing HT especially in patients with CV comorbidities.

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Data availability

Data were obtained by EudraVigilance and Food and Drug Administration Database freely accessible according by European Medicines Agency policies on website https://www.ema.europa.eu/en/human-regulatory/research-development/pharmacovigilance/eudravigilance.

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Author information

Authors and Affiliations

  1. Department of Urology, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy

    Antonio Cicione, Antonio Nacchia, Alessandro Guercio, Carmen Gravina, Antonio Franco, Giorgia Tema, Riccardo Lombardo, Andrea Tubaro & Cosimo De Nunzio

  2. Catholic University of Sacred Heart, Cardiology, Rome, Italy

    Maria Chiara Grimaldi

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Contributions

AC: data collection, project development. AN: manuscript writing, data analysis. AG: data collection. CG: data collection. AF: data collection. MCG: manuscript writing. GT: data collection. RL: data collection. AT: project development. CDN: project development, manuscript writing.

Corresponding author

Correspondence to Cosimo De Nunzio.

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The authors declare no competing interests.

Ethical approval

Ethical approval was waived by the local Ethics Committee of University La Sapienza of Rome in view of the retrospective nature of the study and all the procedures being performed were part of the routine care.

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Cicione, A., Nacchia, A., Guercio, A. et al. Cardiovascular adverse events-related to GnRH agonists and GnRH antagonists: analysis of real-life data from Eudra-Vigilance and Food and Drug Administration databases entries. Prostate Cancer Prostatic Dis 26, 765–771 (2023). https://doi.org/10.1038/s41391-022-00640-4

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