Cardiovascular Effects of GnRH Antagonists Compared With Agonists in Prostate Cancer: A Systematic Review.

Androgen deprivation therapy is the cornerstone of treatment for patients with advanced prostate cancer. Meta-analysis of small, oncology-focused trials suggest gonadotropin-releasing hormone (GnRH) antagonists may be associated with fewer adverse cardiovascular outcomes compared with GnRH agonists.

This study sought to determine whether GnRH antagonists were associated with fewer major adverse cardiovascular events compared with GnRH agonists.

Electronic databases were searched for all prospective, randomized trials comparing GnRH antagonists with agonists. The primary outcome was a major adverse cardiovascular event as defined by the following standardized Medical Dictionary for Regulatory Activities terms: "myocardial infarction," "central nervous system hemorrhages and cerebrovascular conditions," and all-cause mortality. Bayesian meta-analysis models with random effects were fitted.

A total of 11 eligible studies of a maximum duration of 3 to 36 months (median = 12 months) enrolling 4,248 participants were included. Only 1 trial used a blinded, adjudicated event process, whereas potential bias persisted in all trials given their open-label design. A total of 152 patients with primary outcome events were observed, 76 of 2,655 (2.9%) in GnRH antagonist-treated participants and 76 of 1,593 (4.8%) in agonist-treated individuals. Compared with GnRH agonists, the pooled OR of GnRH antagonists for the primary endpoint was 0.57 (95% credible interval: 0.37-0.86) and 0.58 (95% credible interval: 0.32-1.08) for all-cause death.

Despite the addition of the largest, dedicated cardiovascular outcome trial, the volume and quality of available data to definitively answer this question remain suboptimal. Notwithstanding these limitations, the available data suggest that GnRH antagonists are associated with fewer cardiovascular events, and possibly mortality, compared with GnRH agonists.

JACC. CardioOncology. 2023 Aug 01*** epublish ***

Adam J Nelson, Renato D Lopes, Hwanhee Hong, Kaiyuan Hua, Susan Slovin, Sean Tan, Jan Nilsson, Deepak L Bhatt, Shaun G Goodman, Christopher P Evans, Noel W Clarke, Neal D Shore, David Margel, Laurence H Klotz, Bertrand Tombal, Darryl P Leong, John H Alexander, Celestia S Higano

Duke Clinical Research Institute, Durham, North Carolina, USA., Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Monash Heart, Monash Health, Melbourne, Victoria., Department of Clinical Sciences Malmö, Lund University, Sweden., Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York, New York, USA., Division of Cardiology, St. Michael's Hospital, Department of Medicine, University of Toronto, Ontario, Canada., Department of Urologic Surgery, University of California, Davis, Davis, California, USA., Department of Urology, The Christie and Salford Royal Hospitals, Manchester, United Kingdom., Carolina Urologic Research Center, Myrtle Beach, South Carolina, USA., Division of Urology, Rabin Medical Center, Petach Tikva, Israel., Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada., Institut de Recherche Cliniques, Cliniques Universitaires Saint Luc, Brussels, Belgium., Department of Medicine, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada., Division of Medical Oncology, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.