Cardiovascular risk of gonadotropin-releasing hormone antagonist versus agonist in men with prostate cancer: an observational study in Taiwan

Background: The impact of gonadotropin-releasing hormone (GnRH) antagonist and agonist (GnRHa) treatment on cardiovascular disease (CVD) risk in prostate cancer (PCa) remains inconclusive due to conflicting findings. We compared the effects of GnRH antagonist and GnRHa treatments on CVD risk in patients with PCa and pre-existing CVD, in a Taiwan population-based database. Methods: We assessed the risk of major adverse CV events (MACE: ischemic heart disease [IHD], stroke, congestive heart failure [CHF] or all cause deaths) and composite CV events (IHD, stroke, CHF or CV deaths) occurring ≥90 days after androgen deprivation therapy (ADT) initiation in patients with PCa after 90 days of treatment with either GnRH antagonist (degarelix; n = 499) or GnRHa (goserelin, leuprolide, triptorelin; n = 15,127). Patients identified with pre-existing CVD had received cardiac therapy for IHD, reported a stroke or CHF within a year before ADT initiation. Adjusted hazard ratios (aHR) and 95% confidence interval (CI) were obtained for MACE and composite CV events risk after adjusting for age, baseline status of diabetes, hypertension and treatments received. Results: All GnRH antagonist-treated patients showed lower risk of composite CV events than the GnRHa-treated patients. The lower composite CV events risk associated with GnRH antagonist was also observed in patients with metastasis at diagnosis (aHR 0.16; 95% CI, 0.04–0.38; p = 0.013) and those receiving ADT for more than six months (aHR 0.30; 95% CI, 0.16–0.54; p < 0.0001). In patients with pre-existing CVD, the MACE risk was 33% lower (aHR 0.67; 95% CI, 0.46–0.96; p = 0.0299) and composite CV events risk was 84% lower (aHR 0.16; 95% CI, 0.05–0.50; p = 0.0017) in GnRH antagonist-treated than the GnRHa-treated patients. Conclusions: In patients with PCa and pre-existing CVD, GnRH antagonist use was associated with lower risks for composite CV events and MACE compared with GnRHa.