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Kokorovic et al

         PRONOUNCE is a multi-institutional, international, pro-  were followed by a cardiologist and underwent cardiac opti-
       spective, randomized controlled trial whose primary end-  mization for secondary prevention of cardiac events. This
       point was to compare the effect of degarelix and leupro-  strongly suggests that routine monitoring of adverse events
       lide on MACE in patients with prostate cancer and a prior   and optimization of cardiac risk factors throughout ADT
       history of atherosclerotic cardiovascular disease (ASCVD).   treatment may reduce cardiac morbidity associated with
       Patients due to receive ADT for a minimum duration of 12   ADT. This supports the guideline panel’s recommendations
       months were randomized to receive degarelix or leuprolide   for continuous monitoring and optimization of cardiometa-
       in standard doses. The primary endpoint of the study was   bolic parameters in patients receiving ADT, regardless of
       the time from randomization to first occurrence of centrally   whether an agonist or antagonist is used.
       adjudicated MACE, a composite of all-cause death, MI, or
       stroke through 12 months.                             Competing interests: Dr. So has been an advisory board member for Abbvie, Amgen, Astellas,
         The primary outcome of first occurrence of MACE (all-  Bayer, Janssen, Ferring, and TerSera; and has participated in clinical trials supported by Astellas,
       cause death, MI, or stroke) occurred in 15 (5.5%) patients   Ferring, and Janssen. Dr. Izard has received grant(s) or honoraria from Abbvie, Astellas, Bayer,
       receiving degarelix and 11 (4.1%) patients receiving leu-  Ferring, Janssen, and Sanofi; and has participated in clinical trials supported by Abbvie, Astellas,
       prolide (hazard ratio [HR] 1.28, 95% confidence interval   AstraZeneca, Bayer, Janssen, and Merck. Dr. Saad has been an advisory board member for and has
                                                             received payment/honoraria from Abbvie, Amgen, Astellas, Bayer, Janssen, and Sanofi; and has
       [CI] 0.59–2.79, p=0.53). Additional prespecified sensitivity   participated in clinical trials supported by Amgen, Astellas, Bayer, Janssen, and Sanofi. Dr. Shayegan
       analyses and secondary endpoints were analyzed, none of   has been an advisory board member for Astellas, Bayer, and Janssen; and has received a research
       which yielded a difference in event rate between the groups.   grant from Janssen. Dr. Aprikian has been an advisory board member for Abbvie, Astellas, and
       Importantly, using the HERO trial definitions for MACE,    Bayer; and has received grants from Abbvie, Astellas, Bayer, Sanofi, and TerSera. Dr. Rendon has
       there were 18 events in the degarelix group compared to 21   been an advisory board and speakers’ bureau member for and has received honoraria from Abbvie,
       events in the leuprolide group (HR 0.81, 95% CI 0.43–1.53).   Amgen, Astellas, AstraZeneca, Bayer, Ferring, Jansen, and Sanofi. The remaining authors report no
         PRONOUNCE is the first international, multi-institutional,   competing personal or financial interests related to this work.
       randomized controlled trial that prospectively compares the
       cardiovascular risk of a GnRH antagonist vs. an agonist in
       men with prostate cancer. Overall, the trial results suggest   Prior to publication, this guideline update was reviewed and approved by the CUA Guidelines
       there is no added cardiovascular risk in men receiving a   Committee and the CUA Board of Directors.
       GnRH agonist compared to an antagonist.
         The trial has two major limitations. First, patient accrual
       closed early, with only approximately 60% of the targeted   References
       number of patients accrued. Second, the event rate was
       much lower than anticipated (4.8% actual event rate vs.   1.  Kokorovic A, So AI, Serag H, et al. Canadian Urological Association guideline on androgen depriva-
       7.5% anticipated). PRONOUNCE is, therefore, under-       tion therapy: Adverse events and management strategies. Can Urol Assoc J 2021;15:E307-22.
       powered to demonstrate a significant difference in the pri-  2.  Lopes RD, Higano CS, Slovin SF, et al. Cardiovascular safety of degarelix vs. leuprolide in patients with
       mary event rate.                                         prostate cancer: The primary results of the PRONOUNCE randomized trial. Circulation 2021;144:1295-
         Nonetheless, there is key take-away point from the     1307.
       PRONOUNCE study. The overall event rate was low in both   3.  Shore ND, Saad F, Cookson MS, et al. Oral relugolix for androgen deprivation therapy in advanced prostate
       groups at 4.8%, and was, in fact, much lower than what was   cancer. N Engl J Med 2020;382:2187-96.
       observed in the HERO trial, where 17.8% of patients with
       prior MACE receiving leuprolide experienced an additional   Correspondence: Dr. Ricardo Rendon, Department of Urology, Dalhousie, University, Halifax, NS,
       MACE on trial. The lower event rate in PRONOUNCE can
       likely be attributed to the fact that all enrolled participants

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