Long-term Cardiovascular Risks of Gonadotropin-releasing Hormone Agonists and Antagonists: A Population-based Cohort Study.

Gonadotropin-releasing hormone (GnRH) agonists and antagonists, critical medications for prostate cancer (PCa) treatment, may differ in cardiovascular safety. This prospective cohort study aimed to compare the long-term cardiovascular risks between GnRH agonists and antagonists. Patients with PCa receiving GnRH agonists or antagonists during 2013–2021 in Hong Kong were identified. Patients with <6 months' prescriptions, who were switching between drugs, had missing baseline prostate-specific antigen level or had a prior stroke or myocardial infarction were excluded. Patients were followed up until September 2021. The primary outcome was major adverse cardiovascular events (MACE) as in the PRONOUNCE trial (MACE PRONOUNCE), i.e. a composite of all-cause mortality, stroke and myocardial infarction. The secondary outcome was MACE CVM , i.e. a composite of cardiovascular mortality, stroke and myocardial infarction. Inverse probability treatment weighting was used to balance covariates between groups. The Log-rank test was used to compare the cumulative freedom from the primary outcome between groups. In total, 2479 patients were analysed (162 GnRH antagonist users and 2317 agonist users; median age 75.0 years, interquartile range 68.0–81.6 years). Inverse probability treatment weighting achieved good covariate balance between groups. Over a median follow-up duration of 3.0 years (interquartile range 1.7–5.0 years), 1115 patients (45.0%) had MACE PRONOUNCE and 344 (13.9%) had MACE CVM. GnRH agonist users had lower risks of MACE PRONOUNCE (Log-rank P < 0.001) and MACE CVM (Log-rank P = 0.027). However, no differences were observed within 1 year of follow-up (MACE PRONOUNCE : Log-rank P = 0.308; MACE CVM : Log-rank P = 0.357). Among patients without cardiovascular risk factors at baseline, GnRH agonist users had lower risks of MACE PRONOUNCE (Log-rank P < 0.001) and MACE CVM (Log-rank P = 0.001), whereas no differences were observed in those with such risk factor(s) (MACE PRONOUNCE : Log-rank P = 0.569; MACE CVM : Log-rank P = 0.615). GnRH antagonists may be associated with higher long-term, but not short-term, cardiovascular risks than agonists in Asian patients with PCa, particularly in those without known cardiovascular risk factors. • GnRH agents may differ in cardiovascular safety. • 2479 prostate cancer patients receiving GnRH agonists or antagonist were studied. • GnRH antagonist may be associated with higher long-term cardiovascular risks. • Short-term cardiovascular risks did not differ between GnRH agonists and antagonists. • Those without cardiovascular risk factors had a larger increase in long-term risks. [ABSTRACT FROM AUTHOR]