Publication Abstract

Authors: Schmid M, Sammon JD, Reznor G, Kapoor V, Speed JM, Abdollah FA, Sood A, Chun FK, Kibel AS, Menon M, Fisch M, Sun M, Trinh QD

Title: The dose-dependent effect of androgen deprivation therapy for localized prostate cancer on adverse cardiac events.

Journal: BJU Int :-

Date: 2015 Jun 13

Abstract: OBJECTIVES: To investigate the dose-dependent effect of androgen deprivation therapy (ADT) on adverse cardiac events in elderly men with non-metastatic prostate cancer (PCa) stratified according to life expectancy (LE). PATIENTS AND METHODS: 50,384 men diagnosed with localized PCa between 1992 and 2007 were identified within the SEER registry areas. We compared those who did receive ADT vs. those who did not within 2 years of PCa diagnosis, calculated as monthly equivalent doses of Gonadotropin-releasing hormone (GnRH) agonists (<8, ≥8 doses), or orchiectomy. Men were further stratified according to LE (<5, 5-10, >10 years). Adjusted Cox hazard models assessed the risk of new-onset coronary heart disease (CHD), acute myocardial infarction (AMI), sudden cardiac death (SCD), cardiac-related interventions, as well as any of these events. RESULTS: Overall, patients receiving GnRH agonists were more likely to experience a cardiac event, with the most pronounced effect among those receiving ≥8 doses (Hazard ratio [HR] (<8 doses): 1.13, 95% CI: 1.09-1.16, and HR (≥8 doses): 1.18, 95% CI: 1.14-1.22, both p<0.001). The effect of prolonged (≥8 doses) GnRH agonist use on cardiac events was sustained across all strata of LE; however, it was not among men with a LE of <5 years and when use of GnRH agonists was limited to <8 doses (Hazard ratio [HR]: 0.99, 95% CI: 0.67-1.46, p=0.964). The use of GnRH agonists was associated with a higher risk of CHD (HR (<8 doses): 1.13, 95% CI: 1.09-1.17 and HR (≥8 doses): 1.17, 95% CI: 1.13-1.21, both p<0.001). Conversely, the use of GnRH was generally not associated with an increased risk of AMI or SCD, except for men who received ≥8 doses of GnRH agonists and LE of ≥5 years, who were at a significantly higher risk of SCD (HR (LE 5-10y): 1.19, 95% CI: 1.06-1.33, p=0.003 and HR (LE >10y): 1.16, 95% CI 1.04-1.29, p=0.006). Finally, orchiectomy was not associated with overall cardiac events, AMI, SCD, and was protective with regard to cardiac-related interventions (HR: 0.78, 95% CI 0.68-0.90, p=0.001). CONCLUSION: Exposure to ADT with GnRH agonists is associated with increased risk of cardiac events in elderly men with localized PCa and a decent LE. Clinicians should carefully weigh the risks and benefits of ADT in patients with a prolonged LE. Routine screening and lifestyle interventions are warranted in at-risk subpopulations treated with ADT. This article is protected by copyright. All rights reserved.