title: Gonadotropin-releasing hormone blockers and cardiovascular disease risk: analysis of prospective clinical trials of degarelix.
abstract: OBJECTIVE
  We investigated associations of baseline cardiovascular disease risk profile, dosing regimen and treatment duration with incident cardiovascular disease events during androgen deprivation therapy with degarelix in patients with prostate cancer.
  
  
  METHODS
  Data on 1,704 men who participated in a total of 9 clinical trials were pooled for analysis. Patients received treatment with 1-month (20 to 240 mg) or 3-month (240 to 480 mg) doses of degarelix for an average of 22 months. End points were ischemic heart disease, cerebrovascular disorders, arterial thrombotic/embolic events and intermittent claudication.
  
  
  RESULTS
  First time cardiovascular disease events were reported in 92 men in the year before study entry and in 168 after degarelix treatment. Event rates were similar before and after degarelix treatment in the total population (5.5 vs 6.1/100 person-years, p = 0.45) and in men without cardiovascular disease (5.6 vs 4.3/100 person-years, p = 0.11). In contrast, event rates appeared higher after degarelix treatment in men with cardiovascular disease at baseline (5.3 to 10.5 events per 100 person-years, p = 0.0013). On multivariate analysis cardiovascular disease at baseline was the strongest independent predictor of events, followed by older age, alcohol abstinence and obesity (each p <0.05). Degarelix dose and schedule were not independently associated with cardiovascular disease events.
  
  
  CONCLUSIONS
  In men with prostate cancer observed rates of cardiovascular disease events were similar before and after degarelix treatment. Events were largely confined to men with preexisting cardiovascular disease and further modulated by age and modifiable risk factors. Randomized, controlled trials and longer followup are key to fully clarify the comparative safety of gonadotropin-releasing hormone antagonists vs agonists.
authors.affiliation: Hematology-Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA. smith.matthew@mgh.harvard.edu
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
authors.forename: Laurence
authors.initials: L
authors.lastname: Klotz
authors.forename: Egbert
authors.initials: E
authors.lastname: van der Meulen
authors.forename: Enrico
authors.initials: E
authors.lastname: Colli
authors.forename: László B
authors.initials: LB
authors.lastname: Tankó
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000453:epidemiology*; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002986:Clinical Trials as Topic; D015897:Comorbidity; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000453:epidemiology; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology*; D018570:Risk Assessment; D013739:Testosterone / Q000097:blood
chemical_list: D009842:Oligopeptides; C431566:acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone