ASCO GU 2022: Real-World Analyses of Major Adverse Cardiovascular Event Risk by Drug Class After Initiation of ADT

( The 2022 GU ASCO Annual meeting included a prostate cancer session featuring work from Dr. David Crawford and colleagues presenting results of their real-world analyses of major adverse cardiovascular event (MACE) risk by drug class after initiation of ADT. Recent literature has suggested an association between ADT and increased cardiovascular risk in prostate cancer patients. The 1-year incidence of MACE in patients ≥45 years old was 1.4%, whereas a recent study of prostate cancer patients on ADT reported MACE in 2.9% of patients treated with an LHRH antagonist (relugolix), and 6.2% of patients treated with an LHRH agonist (leuprolide acetate) over 48 weeks in the HERO trial.1 Thus, MACE risk is an important consideration for prostate cancer patients on ADT. This study aims to evaluate MACE risk after ADT initiation with LHRH agonists versus LHRH antagonists using real-world data.

Analyses of US electronic medical records (2010 to 2020) of prostate cancer patients (n=45,059) receiving LHRH agonist and antagonist injections were conducted to evaluate the rate of MACE-free survival after ADT initiation by drug class. The database contained 178,388 LHRH agonist and antagonist injection entries and 965 documented MACE events. Exclusion criteria included taking more than one class of ADT and MACE within 6 months prior to ADT initiation:

David Crawford-0.jpg

MACE was defined as myocardial infarction, stroke, and death from any cause (HERO definition1). Kaplan-Meier event-free survival curves were constructed to compare the risk of MACE between patients on agonist versus antagonist. Statistical significance between survival curves was evaluated by log-rank test.

There were 40,292 patients that received an LHRH agonist and 1,894 patients that received an LHRH antagonist this study. Age, BMI, personal history of MACE, family history of MACE, and tobacco use history were comparable between the two groups:

David Crawford-1.jpg

MACE incidence was 1.0% and 1.0% at 1 year and 6.0% and 12.7% at 7 years following ADT initiation for patients treated with LHRH agonists and antagonists, respectively. In the first 7 years after ADT initiation, MACE rate was higher for patients treated with antagonists versus agonists, particularly at year 4 (8% versus 4%; p < 0.05):

David Crawford-2.jpg

Dr. Crawford concluded his presentation of a real-world analysis of MACE risk by drug class after initiation of ADT with the following take-home messages:

  • Risk of MACE was lower than previously reported
  • Although this may potentially be due to underreporting, this data analysis over 10 years from >45,000 prostate cancer patients is likely an accurate reflection of the real world
  • A recent study using a large real-world dataset with >50,000 prostate cancer patients over approximately 2 years showed no difference in cardiovascular risk following treatment with GnRH agonists and antagonists
  • However, in the current analysis, MACE risk was lower in patients treated with LHRH agonists versus antagonists in the first seven years after ADT initiation
  • Further, these investigators plan to evaluate baseline comorbidities and demographics for imbalances
  • Future studies evaluating the impact of ADT class and comorbidities on MACE risk for prostate cancer patients during ADT may be helpful to identify cardiovascular predictors

Presented by: E. David Crawford, MD, University of California San Diego, Koman Family Outpatient Pavilion, San Diego, CA

Co-Authors: Stuart Atkinson, Deborah Boldt-Houle, Lucio N. Gordan 

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022 


  1. Shore ND, Saad F, Cookson MS, et al. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187-2196.