Risk of cardiovascular disease following gonadotropin‐releasing hormone agonists vs antagonists in prostate cancer: Real‐world evidence from five databases. Issue 9 (23rd November 2020)

• Record Type: Journal Article
• Authors: George, Gincy; Garmo, Hans; Scailteux, Lucie‐Marie; Balusson, Frédéric; De Coster, Greet; De Schutter, Harlinde; Kuiper, Josephina G.; Oger, Emmanuel; Verbeeck, Julie; Van Hemelrijck, Mieke
• Is Part Of: International journal of cancer. Volume 148:Issue 9(2021)
• Page Start: 2203
• Page End: 2211
• Publication Date: 2020-11-23
• Subjects: cardiovascular disease -- GnRH agonists -- GnRH antagonists -- prostate cancer -- real‐world evidence; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.33397
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract: Observational studies in prostate cancer (PCa) have shown an increased risk of cardiovascular disease (CVD) following gonadotropin‐releasing hormone (GnRH) agonists, whereas randomised‐controlled trials have shown no associations. Compared to GnRH agonists, GnRH antagonists have shown less atherosclerotic effects in preclinical models. We used real‐world data from five countries to investigate CVD risk following GnRH agonists and antagonists in PCa men. Data sources included cancer registries, primary and secondary healthcare databases. CVD event was defined as an incident or fatal CVD. Multivariable Cox proportional hazard models estimated hazard ratios (HRs) and 95% confidence intervals (CIs), which were pooled using random‐effects meta‐analysis. Stratified analyses were conducted by history of CVD and age (75 years). A total of 48 757 men were on GnRH agonists and 2144 on GnRH antagonists. There was no difference in risk of any CVD for men on GnRH antagonists and agonists (HR: 1.25; 95% CI: 0.96‐1.61; I 2 : 64%). Men on GnRH antagonists showed increased risk of acute myocardial infarction (HR: 1.62; 95% CI: 1.11‐2.35; I 2 : 0%) and arrhythmia (HR: 1.55; 95% CI: 1.11‐2.15, I 2 : 17%) compared to GnRH agonists. Having a history of CVD was found to be an effect modifier for the associations with some CVD subtypes. Overall, we did not observe a difference in risk of overall CVD when comparing GnRH antagonists with agonists—though for some subtypes of CVD we noted an increased risk with antagonists. Further studies are required to address potential confounding caused by unadjusted variables such as severity of CVD history and PCa stage. Abstract : What's new? Prolonged use of gonadotropin‐releasing hormone (GnRH) agonists has been associated with an increased risk of cardiovascular disease (CVD). Preclinical studies have indicated that newer GnRH antagonists may cause fewer atherosclerotic effects than GnRH agonists. In this meta‐analysis of prostate cancer studies, however, the authors found little benefit of GnRH antagonists over GnRH agonists, in terms of CVD risk. If anything, men taking GnRH antagonists may have an increased risk of acute myocardial infarction and arrhythmia compared to GnRH agonists. Further studies are warranted.