title: The impact of androgen-deprivation therapy (ADT) on the risk of cardiovascular (CV) events in patients with non-metastatic prostate cancer: a population-based study.
abstract: OBJECTIVE
  To examine and quantify the contemporary association between androgen-deprivation therapy (ADT) and three separate endpoints: coronary artery disease (CAD), acute myocardial infarction (AMI), and sudden cardiac death (SCD), in a large USA contemporary cohort of patients with prostate cancer.
  
  
  METHODS
  In all, 140 474 patients diagnosed with non-metastatic prostate cancer between 1995 and 2009 within the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database were abstracted. Patients treated with ADT and those not receiving ADT were matched using propensity score methodology. The 10-year CAD, AMI, and SCD rates were estimated. Competing-risks regression analyses tested the association between the type of ADT (GnRH agonists vs bilateral orchidectomy) and CAD, AMI, and SCD, after adjusting for the risk of dying during follow-up.
  
  
  RESULTS
  Overall, the 10-year rates of CAD, AMI, and SCD were 25.9%, 15.6%, and 15.8%, respectively. After stratification according to ADT status (ADT-naïve vs GnRH agonists vs bilateral orchidectomy), the CAD rates were 25.1% vs 26.9% vs 23.2%, the AMI rates were 14.8% vs 16.6% vs 14.8%, and the SCD rates were 14.2% vs 17.7% vs 16.4%, respectively. In competing-risks multivariable regression analyses, the administration of GnRH agonists (all P < 0.001), but not bilateral orchidectomy (all P ≥ 0.7), was associated with higher risk of CAD, AMI, and SCD.
  
  
  CONCLUSIONS
  The administration of GnRH agonists, but not orchidectomy, is still associated with a significantly increased risk of CAD, AMI, and, especially, SCD in patients with non-metastatic prostate cancer. Alternative forms of ADT should be considered in patients at higher risk of CV events.
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada.|Urological Research Institute, Vita-Salute San Raffaele University, San Raffaele Hospital, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gandaglia
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada.
authors.forename: Maxine
authors.initials: M
authors.lastname: Sun
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada.|Department of Urology, University of Montreal Health Center, Montreal, Canada.
authors.forename: Ioana
authors.initials: I
authors.lastname: Popa
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada.|Martini-clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Schiffmann
authors.affiliation: Urological Research Institute, Vita-Salute San Raffaele University, San Raffaele Hospital, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Firas
authors.initials: F
authors.lastname: Abdollah
authors.affiliation: Division of Urologic Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors.forename: Quoc-Dien
authors.identifier: http://orcid.org/0000-0003-3857-9276
authors.initials: QD
authors.lastname: Trinh
authors.affiliation: Department of Urology, University of Montreal Health Center, Montreal, Canada.
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.affiliation: Martini-clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.affiliation: Urological Research Institute, Vita-Salute San Raffaele University, San Raffaele Hospital, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Urological Research Institute, Vita-Salute San Raffaele University, San Raffaele Hospital, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada.|Department of Urology, University of Montreal Health Center, Montreal, Canada.
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D003327:Coronary Disease / Q000453:epidemiology*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000453:epidemiology*; D009919:Orchiectomy; D057216:Propensity Score; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D012307:Risk Factors; D018426:SEER Program; D014481:United States
chemical_list: D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone
keywords: androgen-deprivation therapy; cardiovascular events; prostate cancer; side-effects