Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS)

J Urol. 2021 Sep;206(3):613-622. doi: 10.1097/JU.0000000000001785. Epub 2021 Apr 19.

Abstract

Purpose: The comparative cardiovascular risk profiles of available hormone therapies for the treatment of prostate cancer is not known.

Materials and methods: We queried the U.S. Food and Drug Administration Adverse Event Reporting System, a retrospective, pharmacovigilance database, for cardiovascular adverse event reports in men with prostate cancer receiving gonadotropin releasing hormone (GnRH) agonists, GnRH antagonists, androgen receptor antagonists, and/or androgen synthesis inhibitors from January 2000 to April 2020.

Results: Cardiovascular adverse events accounted for 6,231 reports (12.6%) on hormone monotherapy and 1,793 reports (26.1%) on combination therapy. Arterial vascular events were reported most commonly, followed by arrhythmias, heart failure, and venous thromboembolism. Compared to GnRH agonists, GnRH antagonists were associated with fewer cardiovascular adverse event reports as monotherapy (adjusted reporting odds ratio [ROR]=0.70 [95% CI 0.59-0.84], p <0.001) and as combination therapy (ROR=0.47 [0.34-0.67], p <0.0001), driven by reductions in arterial vascular events. Second generation androgen receptor antagonists and abiraterone were associated with more reports of hypertension requiring hospitalization (ROR=1.21 [1.03-1.41], p=0.02 and ROR=1.19 [1.01-1.40], p=0.03, respectively), and more heart failure events when used in combination with GnRH antagonists (ROR=2.79 [1.30-6.01], p=0.009 and ROR=2.57 [1.12-5.86], p=0.03).

Conclusions: In this retrospective analysis of a pharmacovigilance database, arterial vascular events were the most commonly reported cardiovascular adverse events in men on hormone therapy for prostate cancer. GnRH antagonists were associated with fewer reports of overall cardiovascular events and arterial vascular events than GnRH agonists. Additional study is needed to identify optimal strategies to reduce cardiovascular morbidity among men with prostate cancer receiving hormone therapy.

Keywords: androgen antagonists; pharmacovigilance; prostatic neoplasms.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / adverse effects
  • Androstenes / adverse effects
  • Antineoplastic Agents, Hormonal / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Cross-Sectional Studies
  • Databases, Factual / statistics & numerical data
  • Gonadotropin-Releasing Hormone / agonists
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors
  • Heart Failure / chemically induced
  • Heart Failure / epidemiology*
  • Humans
  • Hypertension / chemically induced
  • Hypertension / epidemiology*
  • Male
  • Middle Aged
  • Pharmacovigilance
  • Prostatic Neoplasms / drug therapy*
  • Retrospective Studies
  • United States / epidemiology
  • United States Food and Drug Administration / statistics & numerical data
  • Young Adult

Substances

  • Androgen Antagonists
  • Androstenes
  • Antineoplastic Agents, Hormonal
  • Gonadotropin-Releasing Hormone
  • abiraterone