Lower odds of cardiac events for gonadotropic releasing hormone antagonists versus agonists
Cone EB, Modonutti D, Reese S, Marchese M, Nabi J, Abdollah F, Kilbridge K, and Trinh QD. Lower odds of cardiac events for gonadotropic releasing hormone antagonists versus agonists. European Urology Open Science 2020; 19:e896.
European Urology Open Science
Introduction & Objectives: Gonadotropic releasing hormone (GnRH) agonists and antagonists are first-line for advanced prostate cancer, but may be associated with cardiac toxicity. Observational studies show a relatively lower risk for GnRH antagonists, but a randomized trial found no difference. We compared the reporting of cardiac events for GnRH agonists and antagonists.
Materials & Methods: We used VigiBase, the World Health Organization global database of case safety reports, which collects data from more than 130 countries to extract drug-adverse event (AE) pairs. Using Medical Dictionary for Regulatory Activities terminology, we identified AEs related to GnRH antagonist (degarelix) or agonist (leuprolide, goserelin, triptorelin, histrelin) therapy for prostate cancer, including myocardial infarction, heart failure, cardiomyopathies, new-onset valvular dysfunction, and other major cardiac events. To explore a possible relationship we used the reporting odds ratio (ROR), a surrogate measure of association using all other reactions as non-cases. A lower bound of a 95% confidence interval of ROR >1 reflects a dis-proportionality signal that more AEs are observed than expected.
Results: We found 10,504 AEs for GnRH agonists, and 1,606 for GnRH antagonists; 805 (7.7%) were cardiac for agonists, and 102 for antagonists (6.4%). We found no signal for overall cardiac events or any sub grouping for GnRH antagonists, but identified a signal both for overall cardiac events (ROR 1.20, 95% CI 1.12-1.29) and myocardial infarction (1.76, 1.57-1.97) for GnRH agonists.
Conclusions: Using validated pharmacovigilance methodology, we found a signal for myocardial infarction for GnRH agonists, but did not detect one for GnRH antagonists. As cardiovascular disease is the most common cause of non-cancer death in prostate cancer patients, this finding is of specific relevance in the current era of novel second-line anti-androgen therapies which may compound toxicity when added to first-line therapy. The relative cardiac toxicity of GnRH agonist therapy compared to GnRH antagonists merits renewed attention.