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 (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.
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).
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.
Clinical oncology (Royal College of Radiologists (Great Britain)). 2023 Mar 29 [Epub ahead of print]
J S K Chan, Y H A Lee, J M H Hui, K Liu, E C Dee, K Ng, P Tang, G Tse, C F Ng
Cardio-oncology Research Unit, Cardiovascular Analytics Group, China-UK Collaboration, Hong Kong, China., Cardio-oncology Research Unit, Cardiovascular Analytics Group, China-UK Collaboration, Hong Kong, China; Division of Urology, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China., Division of Urology, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China., Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London, UK., Cardio-oncology Research Unit, Cardiovascular Analytics Group, China-UK Collaboration, Hong Kong, China; Kent and Medway Medical School, Canterbury, UK; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China; School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, China. Electronic address: ., Division of Urology, Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; SH Ho Urology Centre, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: .