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

No AccessJournal of UrologyAdult Urology1 Sep 2021Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS)This article is commented on by the following:Editorial CommentEditorial Comment Kathleen W. Zhang, Melissa A. Reimers, Adam Christopher Calaway, Michael G. Fradley, Lee Ponsky, Jorge A. Garcia, Jennifer Cullen, Brian C. Baumann, Daniel Addison, Courtney M. Campbell, Arjun K. Ghosh, Daniel J. Lenihan, Nihar R. Desai, Neal Weintraub, and Avirup Guha Kathleen W. ZhangKathleen W. Zhang *Correspondence: Cardio-Oncology Center of Excellence, Cardiovascular Division, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8086, St. Louis, Missouri 63110-1093 telephone: 314-362-1291; FAX: 314-747-1417; E-mail Address: [email protected] http://orcid.org/0000-0002-5033-6798 Cardio-Oncology Center of Excellence, Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri Financial and/or other relationship with Eidos Therapeutics. More articles by this author , Melissa A. ReimersMelissa A. Reimers Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri More articles by this author , Adam Christopher CalawayAdam Christopher Calaway Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio More articles by this author , Michael G. FradleyMichael G. Fradley Cardio-Oncology Center of Excellence, Division of Cardiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Financial and/or other relationship with Takeda, Abbott and Medtronic. More articles by this author , Lee PonskyLee Ponsky Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio More articles by this author , Jorge A. GarciaJorge A. Garcia Division of Oncology, Seidman Cancer Center, Cleveland, Ohio Paid consultant for Bayer/Sanofi Aventis, Seattle Genetics, Janssen, Merck, MJH and Eisai; supported by research grants from Merck, Janssen, Seattle Genetics and Pfizer. More articles by this author , Jennifer CullenJennifer Cullen Department of Population and Quantitative Health Sciences, Case Comprehensive Cancer Center, Cleveland, Ohio More articles by this author , Brian C. BaumannBrian C. Baumann Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri Financial and/or other relationship with Mevion Medical Systems (honoraria) and Sanofi/Regeneron (Medical Advisory Board). More articles by this author , Daniel AddisonDaniel Addison Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio More articles by this author , Courtney M. CampbellCourtney M. Campbell Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio Supported by National Center for Advancing Translational Sciences (National Institutes of Health) Award Number Grant TL1TR002735. More articles by this author , Arjun K. GhoshArjun K. Ghosh Cardio-Oncology Service, Barts Heart Centre, St. Bartholomew’s Hospital West Smithfield, London, United Kingdom More articles by this author , Daniel J. LenihanDaniel J. Lenihan Cardio-Oncology Center of Excellence, Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri Financial and/or other relationship with Myocardial Solutions; consultant fees, modest, for AstraZeneca, Prothena, Eidos, Clementia, Cytokinetics, Lilly and Roche. More articles by this author , Nihar R. DesaiNihar R. Desai Cardiovascular Medicine Section, Yale School of Medicine, New Haven, Connecticut Financial and/or other relationship with Amgen, Astra Zeneca, Boehringer Ingelheim, Cytokinetics, Relypsa, Novartis, MyoKardia and SC Pharmaceuticals. More articles by this author , Neal WeintraubNeal Weintraub Division of Cardiovascular Medicine, Augusta University, Augusta, Georgia More articles by this author , and Avirup GuhaAvirup Guha Harrington Heart and Vascular Institute, Case Western Reserve University School of Medicine, Cleveland, Ohio More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001785AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail 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. References 1. : The diagnosis and treatment of prostate cancer: a review. JAMA 2017; 317: 2532. Google Scholar 2. : Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012; 367: 203. Google Scholar 3. : A population-based study of cardiovascular disease mortality risk in US cancer patients. Eur Heart J 2019; 40: 3889. Google Scholar 4. : Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 2006; 24: 4448. Google Scholar 5. : Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. J Natl Cancer Inst 2007; 99: 1516. Google Scholar 6. : Long-term follow-up of a randomized trial of radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA 2016; 314: 1291. Google Scholar 7. : Cardiovascular complications of prostate cancer therapy. Curr Treat Options Cardiovasc Med 2020; 22: 69. Google Scholar 8. : Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist. Eur Urol 2014; 65: 565. Google Scholar 9. : Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association. Circulation 2010; 121: 833. Google Scholar 10. U.S. Food and Drug Administration:FDA Drug Safety Communication: Ongoing Safety Review of GnRH Antagonists and Possible Increased Risk of Diabetes and Certain Cardiovascular Diseases. Available at: https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-ongoing-safety-review-gnrh-agonists-and-possible-increased-risk. Accessed November 15, 2020. Google Scholar 11. : Cardiovascular morbidity in a randomized trial comparing GnRH agonist and GnRH antagonist among patients with advanced prostate cancer and preexisting cardiovascular disease. J Urol 2019; 202: 1199. Link, Google Scholar 12. : Oral relugolix for androgen-deprivation therapy in advanced prostate cancer. N Engl J Med 2020; 382: 2187. Google Scholar 13. Frequently Asked Questions (FAQ) on FDA's Adverse Event Reporting System (FAERS). U.S. Food and Drug Administration 2018. Available at https://fis.fda.gov/extensions/fpdwidgets/2e01da82-13fe-40e0-8c38-4da505737e36.html. Accessed November 20, 2020. Google Scholar 14. : Cardiovascular safety of degarelix versus leuprolide for advanced prostate cancer. JACC CardioOncology 2020; 2: 70. Google Scholar 15. : The incidence and relative risk of cardiovascular toxicity in patients treated with new hormonal agents for castration-resistant prostate cancer. Eur J Cancer 2015; 51: 1970. Google Scholar 16. : The cardiovascular toxicity of abiraterone and enzalutamide in prostate cancer. Clin Genitourin Cancer 2018; 16: e645. Google Scholar 17. : Increased risk of hypertension with enzalutamide in prostate cancer: a meta-analysis. Cancer Invest 2019; 37: 478. Google Scholar 18. : Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol 2016; 17: 153. Google Scholar 19. : Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2020; 382: 21971. Google Scholar 20. : Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017; 377: 1319. Google Scholar 21. : Cardiovascular risk in men with prostate cancer: insights from the RADICAL PC study. J Urol 2020; 203: 1109. Link, Google Scholar © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited ByZhang K and Guha A (2021) Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS). Reply.Journal of Urology, VOL. 207, NO. 1, (243-243), Online publication date: 1-Jan-2022.Kaplan-Marans E (2021) Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS). Letter.Journal of Urology, VOL. 207, NO. 1, (242-243), Online publication date: 1-Jan-2022.Related articlesJournal of UrologyJun 4, 2021, 12:00:00 AMEditorial CommentJournal of UrologyJun 4, 2021, 12:00:00 AMEditorial Comment Volume 206Issue 3September 2021Page: 613-622Supplementary Materials Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.Keywordsandrogen antagonistspharmacovigilanceprostatic neoplasmsMetricsAuthor Information Kathleen W. Zhang Cardio-Oncology Center of Excellence, Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri *Correspondence: Cardio-Oncology Center of Excellence, Cardiovascular Division, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8086, St. Louis, Missouri 63110-1093 telephone: 314-362-1291; FAX: 314-747-1417; E-mail Address: [email protected] Financial and/or other relationship with Eidos Therapeutics. More articles by this author Melissa A. Reimers Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri More articles by this author Adam Christopher Calaway Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio More articles by this author Michael G. Fradley Cardio-Oncology Center of Excellence, Division of Cardiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania Financial and/or other relationship with Takeda, Abbott and Medtronic. More articles by this author Lee Ponsky Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio More articles by this author Jorge A. Garcia Division of Oncology, Seidman Cancer Center, Cleveland, Ohio Paid consultant for Bayer/Sanofi Aventis, Seattle Genetics, Janssen, Merck, MJH and Eisai; supported by research grants from Merck, Janssen, Seattle Genetics and Pfizer. More articles by this author Jennifer Cullen Department of Population and Quantitative Health Sciences, Case Comprehensive Cancer Center, Cleveland, Ohio More articles by this author Brian C. Baumann Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri Financial and/or other relationship with Mevion Medical Systems (honoraria) and Sanofi/Regeneron (Medical Advisory Board). More articles by this author Daniel Addison Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio More articles by this author Courtney M. Campbell Cardio-Oncology Program, Division of Cardiology, The Ohio State University Wexner Medical Center, Columbus, Ohio Supported by National Center for Advancing Translational Sciences (National Institutes of Health) Award Number Grant TL1TR002735. More articles by this author Arjun K. Ghosh Cardio-Oncology Service, Barts Heart Centre, St. Bartholomew’s Hospital West Smithfield, London, United Kingdom More articles by this author Daniel J. Lenihan Cardio-Oncology Center of Excellence, Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri Financial and/or other relationship with Myocardial Solutions; consultant fees, modest, for AstraZeneca, Prothena, Eidos, Clementia, Cytokinetics, Lilly and Roche. More articles by this author Nihar R. Desai Cardiovascular Medicine Section, Yale School of Medicine, New Haven, Connecticut Financial and/or other relationship with Amgen, Astra Zeneca, Boehringer Ingelheim, Cytokinetics, Relypsa, Novartis, MyoKardia and SC Pharmaceuticals. More articles by this author Neal Weintraub Division of Cardiovascular Medicine, Augusta University, Augusta, Georgia More articles by this author Avirup Guha Harrington Heart and Vascular Institute, Case Western Reserve University School of Medicine, Cleveland, Ohio More articles by this author Expand All Advertisement PDF DownloadLoading ...