Although a recent meta-analysis suggested that gonadotropin-releasing hormone (GnRH) antagonists lead to fewer major adverse cardiovascular events (MACE) compared with luteinizing hormone-releasing hormone (LHRH) agonists, a new real-world study finds the opposite: higher MACE risk with GnRH antagonist use. Investigators presented the findings at the Society of Urologic Oncology 24nd Annual Meeting in Washington, DC.
Our analysis of data from [approximately] 45,000 PCa patients collected over the most recent decade likely reflects real-world outcome patterns, according to Tanya Dorff, MD, of the City of Hope National Medical Center, Duarte, California, and colleagues.
The investigators examined MACE and all-cause mortality risk among men receiving at least 1 dose of an GnRH antagonist or LHRH agonist (99% from 2010-2020) from the Decision Resources Group database.
Based on data from 40,753 men, MACE risk was a significant 1.6-fold higher for GnRH antagonist recipients vs LHRH agonist recipients in an adjusted analysis, Dr Dorff reported on behalf of her team. Based on data from 41,765 men, all-cause mortality risk was a significant 1.8-fold higher for GnRH antagonist vs LHRH agonist users in an adjusted analysis.
Adjusted analyses accounted for age, body mass index, personal and family MACE history, statin use, tobacco history, history of diabetes and/or hypertension, antagonist vs agonist use, baseline PSA, oncology vs urology setting, and race and ethnicity.
In this real-world claims database, overall MACE and mortality risk both increased consistently by 4-5% per year during the first 4 years after ADT initiation, Dr Dorff and colleagues reported. Due to the inherent limitations of retrospective observational studies, further detailed studies are needed to explain any differences in these risks for GnRH antagonist vs LHRH agonist users. ADT duration and concomitant use of androgen receptor pathway inhibitors are important factors.
The median age of the cohort was 75 years. Black and Asian men accounted for 12.7% and 1.3% of patients, respectively. The antagonist and agonist groups had comparable proportions of patients with MACE history (3.4% vs 3.0%). MACE incidence was higher among White than Black and Asian patients initiating androgen deprivation therapy (ADT): 4.0% vs. 2.4% vs 2.2%, respectively, at 1 year after ADT initiation and 21.0% vs 13.3% vs 11.7%, respectively, at 4 years.
As patients initiating ADT likely have a high burden of underassessed and untreated CV risk factors, clinicians should focus on monitoring and treating comorbidities to reduce mortality risk in PCa patients on ADT, the authors concluded in a poster presentation.
Disclosure: This research was supported by Tolmar inc. Please see the original reference for a full list of disclosures.
References
Dorff T, Boldt-Houle DM, Daughtery R, Atkinson SN, Rhee JW. Real-world analyses of MACE and mortality risk in patients with prostate cancer after initiation of LHRH agonists vs GNRH antagonists. Presented at the Society of Urologic Oncology 24nd annual meeting, November 28-December 1, 2023. Poster 42.
Nelson AJ, Lopes RD, Hong H, et al. Cardiovascular effects of GnRH antagonists compared with agonists in prostate cancer: a systematic review. JACC CardioOncol. 2023 Aug 1;5(5):613-624. doi:10.1016/j.jaccao.2023.05.011
Dorff T, Rhee JW. Cardiovascular toxicity during advanced prostate cancer treatment: Minding the heart. JACC CardioOncol. 2023 Oct 17;5(5):625-627. doi:10.1016/j.jaccao.2023.07.005
Topics: Androgen-deprivation Therapy Cardiovascular Disease Medications Myocardial Infarction Stroke SUO 2023 Urology Conferences
