Long-term cardiovascular risks of gonadotropin-releasing hormone agonists and antagonists: A population-based cohort study Journal Article


Authors: Chan, J. S. K.; Lee, Y. H. A.; Hui, J. M. H.; Liu, K.; Dee, E. C.; Ng, K.; Tang, P.; Tse, G.; Ng, C. F.
Article Title: Long-term cardiovascular risks of gonadotropin-releasing hormone agonists and antagonists: A population-based cohort study
Abstract: Aims: 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. Materials and methods: 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 (MACEPRONOUNCE), i.e. a composite of all-cause mortality, stroke and myocardial infarction. The secondary outcome was MACECVM, 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. Results: 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 MACEPRONOUNCE and 344 (13.9%) had MACECVM. GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.027). However, no differences were observed within 1 year of follow-up (MACEPRONOUNCE: Log-rank P = 0.308; MACECVM: Log-rank P = 0.357). Among patients without cardiovascular risk factors at baseline, GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.001), whereas no differences were observed in those with such risk factor(s) (MACEPRONOUNCE: Log-rank P = 0.569; MACECVM: Log-rank P = 0.615). Conclusions: 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. © 2023
Keywords: adult; aged; aged, 80 and over; major clinical study; cancer patient; follow up; prospective study; prospective studies; prostate specific antigen; cohort studies; cohort analysis; risk factors; risk factor; gonadorelin; prostate cancer; prostatic neoplasms; prescription; population research; cardiovascular disease; heart infarction; stroke; cardiovascular diseases; prostate tumor; androgen antagonists; hormonal therapy; antiandrogen; gonadorelin agonist; androgen deprivation therapy; gonadotropin-releasing hormone; myocardial infarction; cerebrovascular accident; gonadorelin antagonist; cohort; cardiovascular risk factor; clinical outcome; hong kong; cardiovascular mortality; very elderly; humans; human; male; article; cardio-oncology; all cause mortality; heart disease risk factors; mace; heart disease risk factor
Journal Title: Clinical Oncology
Volume: 35
Issue: 6
ISSN: 0936-6555
Publisher: Elsevier Science, Inc.  
Date Published: 2023-06-01
Start Page: e376
End Page: e383
Language: English
DOI: 10.1016/j.clon.2023.03.014
PUBMED: 37031076
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 31 May 2023 -- Source: Scopus
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  1. Edward Christopher Dee
    261 Dee