Background: Controversy exists regarding the risk of cardiovascular disease (CVD) associated with androgen deprivation therapy (ADT) in patients with prostate cancer. We sought to evaluate the association between gonadotropin-releasing hormone (GnRH) agonists versus GnRH antagonist and the risk of CVD in patients with prostate cancer with or without prior CVD. Patients and Methods: Using administrative databases from Quebec, Canada, we identified first-time GnRH agonists and antagonist (degarelix) users between January 2012 and June 2016. Follow-up ended at the earliest of the following: first CVD event (myocardial infarction [MI], stroke, ischemic heart disease [IHD], arrhythmia, and heart failure [HF]); switch of GnRH group; death; or December 31, 2016. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to control for potential confounding. IPTW-Cox proportional hazards model accounting for competing risks was used to evaluate the association of interest. Results: Among 10,785 patients identified, 10,201 and 584 were on GnRH agonists and antagonist, respectively. Median age was 75 years (interquartile range, 69–81 years) for both groups. A total of 4,152 (40.7%) men in the GnRH agonists group and 281 (48.1%) men in the GnRH antagonist group had CVD in the 3-year period prior to ADT initiation. Risk of HF was decreased in the antagonist group compared with the GnRH agonist group among patients with prior CVD (hazard ratio [HR], 0.46; 95% CI, 0.26–0.79). Risk of IHD was decreased in the antagonist group in patients without prior CVD (HR, 0.26; 95% CI, 0.11–0.65). Use of antagonist was associated with an increased risk of arrhythmia among patients with no prior CVD (HR, 2.34; 95% CI, 1.63–3.36). Conclusions: Compared with GnRH agonists, the GnRH antagonist was found to be associated with a decreased risk of HF, specifically among patients with prior CVD. Among those with no prior CVD, the GnRH antagonist was associated with a decreased risk of IHD but an increased risk of arrhythmia.
Submitted April 5, 2022; final revision received September 28, 2022; accepted for publication September 29, 2022.
Author contributions: Study concept and design: Dragomir, Aprikian. Data collection: Dragomir, Touma. Analysis and interpretation of results: All authors. Manuscript preparation and/or critical revision: All authors.
Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.
Funding: Alice Dragomir is a recipient of the FRQ-S Chercheur boursier Junior 2 award. Jason Hu is a recipient of the FRQ-S–doctoral program bursary. This study was funded by the Rossy Cancer Network and by the Réseau québécois de recherche sur les médicaments.