The cardiovascular effects of gonadotropin-releasing hormone antagonists in men with prostate cancer

Abstract

Aims The aim of this study was to determine whether gonadotropin-releasing hormone (GnRH) antagonists (an emerging class of drugs to suppress testosterone synthesis in the treatment of prostate cancer) cause less adverse cardiovascular events than the more commonly use GnRH agonists. Methods and Results We conducted a systematic review to identify all randomised, controlled trials in which a GnRH antagonist was compared with a GnRH agonist in men with prostate cancer. We identified ten eligible studies including two different GnRH antagonists, degarelix (n = 1681) and relugolix (n = 734), which were compared with the GnRH agonists, leuprolide (n = 714) and goserelin (n = 600). The pooled risk ratios (95% confidence intervals) among GnRH antagonist recipients for adverse cardiovascular events, cardiovascular death and all-cause mortality were 0.57 (0.39-0.81); 0.49 (0.25-0.96); and 0.48 (0.28-0.83) respectively. Important limitations of the included trials were their short duration of follow-up, unblinded study design and (in most of the studies) the identification of adverse cardiovascular events through safety reporting mechanisms rather than as a pre-specified outcome. There was no evidence of heterogeneity of findings among the studies. Conclusions There is consistent but methodologically limited data to suggest that GnRH antagonists – a relatively new class of androgen deprivation therapy for prostate cancer – cause significantly less cardiovascular adverse effects than the more frequently used GnRH agonists.

HbA1c Variability and Cardiovascular Events in Patients with Prostate Cancer Receiving Androgen Deprivation Therapy

“…Additionally, the observational nature of this study predisposed to residual and unmeasured confounders. Specifically, some studies have suggested that gonadotropin-releasing hormone agonists and antagonists may differ in the risk of MACEs [32] , although this has remained highly controversial following the publication of the PRONOUNCE trial, the first randomised controlled trial specifically designed to compare the cardiovascular safety of gonadotropin-releasing hormone agonists and antagonists, which found no significant difference in the risk of MACEs between these agents [33] . Moreover, cancer staging, histology, disease risk profile, and individual indications for specific treatment regimens were not available.…”

Does Exist a Differential Impact of Degarelix Versus LHRH Agonists on Cardiovascular Safety? Evidences From Randomized and Real-World Studies

“…Cirne et al (22) in their recent meta-analysis included also other studies such as the CS35A trial where data are presented only in abstract, and the HERO trial with relugolix was used as GnRH antagonist (Shore NEJM 2020). This meta-analysis was focused on CVD rates underlying that only in three out of ten randomized trials the prevalence of CVD at baseline was described.…”

Non‐cancer mortality in elderly prostate cancer patients treated with combination of radical prostatectomy and external beam radiation therapy

“…Nonetheless, the objective within the urological community involved in the care of these patients, should be considered both scenarios with the intend of reducing OCM rates either at the time of RP and EBRT selection, based on OCM risk and/or susceptibility to ADT plus EBRT and ADT toxicity. [18][19][20][21][22][23][24] Fourth Our study has limitations and should firstly be interpreted in the context of its retrospective and population-based design. Secondly, no distinction could be made according to adjuvant or salvage EBRT after RP.…”