title: Androgen deprivation therapy and cardiovascular risk: No meaningful difference between GnRH antagonist and agonists-a nationwide population-based cohort study based on 2010-2013 French Health Insurance data.
abstract: Observational studies suggested that androgen deprivation therapy (ADT) is associated with an increased cardiovascular (CV) risk. They all compared ADT-treated cancer patients to non-treated patients or non-cancer subjects. Our aim was to evaluate whether CV risk differs by type of ADT.
  
  
  
  Through nationwide population-based claims reimbursement database linked to hospital discharge database, we identified adult men with prostate cancer who initiated ADT (gonadotrophin releasing hormone [GnRH] agonist or antagonist, antiandrogen [AA], combined androgen blockade [CAB]) or had orchiectomy (OT) between 1st July, 2010, and the 31st December, 2011, and followed them up to 31st December, 2013. The main analysis followed an 'on-treatment' approach that censored all patients at the time of first therapeutic modification; it used Cox regression analysis to estimate hazard ratios (HRs) for hospitalisations for ischaemic events (myocardial infarction or ischaemic stroke, whichever came first), adjusted on age, baseline co-morbidities and taking into account death as a competing risk.
  
  
  
  Among the 35,118 new ADT users, 71% received GnRH agonist (reference group), 12% CAB, 13% AA, 3.6% GnRH antagonist and 0.6% had OT. CAB was associated with an increased risk (adjusted HR [95% confidence interval {CI}], 1.6 [1.3-2.0]) and AA with a decreased risk (adjusted HR [95% CI], 0.6 [0.4-0.9]) of ischaemic events when compared to GnRH agonist. No significant association was found with GnRH antagonist (adjusted HR [95% CI], 1.2 (0.7-2.1)).
  
  
  
  CV risk appeared different across ADT modalities. The probability of a clinically meaningful difference when comparing GnRH antagonists to agonists appears rather low. In a context where better overall and cancer specific survival without worsening quality of life is a challenge for clinicians, a potential heterogeneity in CV morbidity becomes crucial when choosing an ADT.
authors.affiliation: Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France. Electronic address: luciemarie.scailteux@chu-rennes.fr.
authors.forename: Lucie-Marie
authors.initials: LM
authors.lastname: Scailteux
authors.affiliation: Urology Department, Rennes University Hospital, Rennes, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Vincendeau
authors.affiliation: PEPS Research Consortium, Rennes Hospital University, Rennes, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Balusson
authors.affiliation: Cardiology Department, Rennes University Hospital, Rennes, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Leclercq
authors.affiliation: PEPS Research Consortium, Rennes Hospital University, Rennes, France.
authors.forename: André
authors.initials: A
authors.lastname: Happe
authors.affiliation: PEPS Research Consortium, Rennes Hospital University, Rennes, France.
authors.forename: Béranger
authors.initials: B
authors.lastname: Le Nautout
authors.affiliation: Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France; PEPS Research Consortium, Rennes Hospital University, Rennes, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Polard
authors.affiliation: PEPS Research Consortium, Rennes Hospital University, Rennes, France; Université Européenne de Bretagne, Université de Brest, INSERM CIC 1412, IFR 148 et CHU de Brest, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Nowak
authors.affiliation: Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes, France; PEPS Research Consortium, Rennes Hospital University, Rennes, France; UPRES, EA 7449, REPERES "Research in Pharmacoepidemiology and Access to Care", Rennes, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Oger
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D004812:Epidemiologic Methods; D005602:France / Q000453:epidemiology; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced* / Q000401:mortality; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D020521:Stroke / Q000139:chemically induced* / Q000401:mortality
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D007987:Gonadotropin-Releasing Hormone
keywords: Androgen deprivation therapy; Cardiovascular morbidity; Cardiovascular risk; Ischaemic events; Prostate cancer