title: Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist.
abstract: BACKGROUND
  Androgen deprivation therapy (ADT) is associated with increased cardiovascular morbidity.
  
  
  OBJECTIVE
  To determine whether cardiovascular morbidity differs following initiation of gonadotropin-releasing hormone (GnRH) agonists compared with an antagonist.
  
  
  METHODS
  Pooled data from six phase 3 prospective randomized trials that recruited 2328 men between 2005 and 2012 to compare the efficacy of GnRH agonists against an antagonist. Men recruited had pathologically confirmed prostate cancer, an Eastern Cooperative Oncology Group score <2, a minimum life expectancy of 12 mo, and were naïve to ADT. Men were excluded if they had a prolonged baseline QT/corrected QT interval, other risk factors for heart failure, hypokalemia or a family history of long QT syndrome, or had another cancer diagnosed within 5 yr.
  
  
  METHODS
  Men were randomized to receive a GnRH agonist or an antagonist for either 3-7 mo (n=642) or 12 mo (n=1686). Treatment groups were balanced for common baseline characteristics.
  
  
  METHODS
  Event analysis was based on death from any cause or cardiac events. Data documenting adverse experiences were classified based on the Medical Dictionary for Regulatory Activities. The following conditions defined a cardiac event: arterial embolic or thrombotic events, hemorrhagic or ischemic cerebrovascular conditions, myocardial infarction, and other ischemic heart disease. Kaplan-Meier curves and log-rank tests were used to compare time to a cardiovascular event or death.
  
  
  CONCLUSIONS
  Among men with preexisting cardiovascular disease, the risk of cardiac events within 1 yr of initiating therapy was significantly lower among men treated with a GnRH antagonist compared with GnRH agonists (hazard ratio: 0.44; 95% confidence interval, 0.26-0.74; p=0.002). Since our analysis is post hoc, our findings should only be interpreted as hypothesis generating.
  
  
  CONCLUSIONS
  GnRH antagonists appear to halve the number of cardiac events experienced by men with preexisting cardiovascular disease during the first year of ADT when compared to GnRH agonists.
authors.affiliation: University of Connecticut Health Center, Farmington, CT, USA. Electronic address: Albertsen@nso.uchc.edu.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Albertsen
authors.affiliation: Division of Urology, University of Toronto, ON, Canada.
authors.forename: Laurence
authors.initials: L
authors.lastname: Klotz
authors.affiliation: University Clinics Saint Luc/Catholic University of Louvain, Brussels, Belgium.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tombal
authors.affiliation: University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: James
authors.initials: J
authors.lastname: Grady
authors.affiliation: Ferring Pharmaceuticals, Copenhagen, Denmark.
authors.forename: Tine K
authors.initials: TK
authors.lastname: Olesen
authors.affiliation: Department of Clinical Sciences, Lund University, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
mesh_terms: D002318:Cardiovascular Diseases / Q000139:chemically induced*; D017326:Clinical Trials, Phase III as Topic; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment
chemical_list: D007987:Gonadotropin-Releasing Hormone
keywords: Androgen deprivation therapy; GnRH antagonist; Prostate cancer