Background: Recent literature has suggested an association between androgen deprivation therapy (ADT) and increased cardiovascular (CV) risk in prostate cancer (PCa) patients.^1,2 The 1-year incidence of major adverse cardiovascular events (MACE) in patients ≥45 years old was 1.4%,³ whereas a recent study of PCa patients on ADT reported MACE in 2.9% of patients treated with an LHRH antagonist (relugolix) and 6.2% of patients treated with an LHRH agonist (leuprolide acetate) over 48 weeks.⁴ Thus, MACE risk is an important consideration for PCa patients on ADT. This study aims to evaluate MACE risk after ADT initiation with LHRH agonists vs. LHRH antagonists using real-world data. Methods: Analyses of US electronic medical records (2010 to 2020) of PCa patients (n=45,059) receiving LHRH agonist and antagonist injections were conducted to evaluate the rate of MACE-free survival after ADT initiation by drug class. The database contained 178,388 LHRH agonist and antagonist injection entries and 965 documented MACE events. Exclusion criteria included taking more than one class of ADT and MACE within 6 months prior to ADT initiation. MACE was defined as myocardial infarction, stroke, and death from any cause based on a recent study in this field.⁴ Kaplan-Meier event-free survival curves were constructed to compare the risk of MACE between patients on agonist vs. antagonist. Statistical significance between survival curves was evaluated by log-rank test. Results: Overall MACE risk for all patients was 1.0% at one year. MACE risk was significantly higher for patients treated with LHRH antagonist compared to agonists in the first seven years after ADT initiation. Conclusions: Risk of MACE was lower than previously reported. Although this may potentially be due to underreporting, our analysis of data over 10 years from >45,000 PCa patients is likely an accurate reflection of the real world. A recent study using large real-world dataset with >50,000 PCa patients over approximately 2 years showed no difference in CV risk following treatment with GnRH agonists and antagonists.⁵ However, in our analyses MACE risk was lower in patients treated with LHRH agonists vs. antagonists in the first seven years after ADT initiation. Further, we plan to evaluate baseline comorbidities and demographics for imbalances. Future studies evaluating the impact of ADT class and comorbidities on MACE risk for PCa patients during ADT may be helpful to identify CV predictors. ¹Ng C-F, et al. Scientific Reports. 2020. ²Zhao J, et al. PLoS One. 2014. ³Miao B, et al. J of the American Heart Association. 2020. ⁴Shore ND, et al. New England Journal of Medicine. 2020. ⁵George G, et al. Int J Cancer. 2021.