GnRH antagonist users had 36-37% lower 2- and 3-point MACE prevalence (2.3 vs 3.6 and 2.6 vs 4.1 per 100 person-years) than agonist users in real-world ADT.
Do GnRH antagonists reduce the rate of major adverse cardiac events compared to GnRH agonists in men with prostate cancer receiving androgen deprivation therapy?
In real-world practice, men with prostate cancer receiving GnRH antagonists had numerically lower rates of major adverse cardiac events compared to those receiving GnRH agonists.
107 Background: Androgen deprivation therapy (ADT) is the backbone treatment for advanced prostate cancer (PC), but it has been associated with an increased risk of major adverse cardiac events (MACE), especially in men with pre-existing cardiovascular (CV) disease. The oral gonadotropin-releasing hormone (GnRH) receptor antagonist, relugolix, was approved in December 2020 based on the HERO trial. After 48 weeks of treatment, there was a 54% lower risk of MACE with relugolix compared with leuprolide. However, the prevalence of MACE in real-world clinical practice is unknown. This observational study evaluated the real-world prevalence of MACE among men receiving ADT in the United States. Methods: Men with PC who newly initiated ADT between January 2018 and May 2024 were identified in the Merative MarketScan Commercial and Medicare Databases. The first ADT claim was the index date, and men were followed for a 12-month pre-index and ≥60-day post-index period, defined by duration of ADT. Primary outcomes included the rate of 2- and 3-point MACE (non-fatal myocardial infarction or stroke 2- and 3-point, or all-cause death 3-point). Demographics and baseline characteristics were also assessed. Reporting was carried out for the entire group, men who initiated GnRH agonists (eg, leuprolide) or antagonists (eg, degarelix, relugolix), and men who started ADT before or after relugolix approval (January 2021). Patients who initiated degarelix but switched to an agonist within 60 days were classified as agonist users. Results: Of 17,336 men newly initiating ADT, 90.4% (15,666) received a GnRH agonist, and 9.6% (1670) received a GnRH antagonist; 624 (3.6% of all patients) received relugolix. The overall median age was 69 years. Men treated with GnRH antagonists vs agonists were younger (65.5 vs 69.0 years), more likely to be commercially insured (48.3% vs 40.6%), and had a shorter follow-up (126 vs 189 days). Prevalence of 2- and 3-point MACE over the study period was 3.5 and 4.0 per 100 person-years, respectively. Antagonist vs agonist users had a 36% and 37% lower prevalence of 2-point (2.3 vs 3.6) and 3-point (2.6 vs 4.1) MACE, respectively. Prevalence of 2- and 3-point MACE decreased over the study period from 3.7 and 4.2 per 100 person-years in 9254 men (53.4%) who initiated ADT before January 1, 2021, to 3.3 and 3.7 per 100 person-years in 8082 men (46.6%) who initiated ADT after January 1, 2021. An increase in GnRH antagonist use was seen from 6.6% before January 1, 2021, to 13.2% after. Conclusions: In practice, MACE prevalence remained low after initiating ADT. Although differences in baseline characteristics remain, MACE rates were numerically lower in men receiving GnRH antagonists. Use of GnRH antagonists increased following relugolix approval and coincided with a greater awareness of CV risk factors, potentially leading to a decline in MACE rates.
Hahn et al. (2026) studied this question. GnRH antagonist users had 36-37% lower 2- and 3-point MACE prevalence (2.3 vs 3.6 and 2.6 vs 4.1 per 100 person-years) than agonist users in real-world ADT.
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