In the USA, the Food and Drug Administration (FDA) collects data on adverse health events associated with a variety of prescription drugs. Researchers recently interrogated that database to look at what sorts of serious cardiovascular events have been reported for prostate cancer patients on various ADT agents when used either alone or in combination.
The researchers confirmed the often-reported elevated risk of an arterial vascular event with the LHRH agonists (e.g., Lupron and Zoladex). That would include the serious stuff, like heart attacks and strokes. But the data revealed much more than that.
Arterial vascular events are just one category of cardiovascular diseases (CVD). There are others, such as arrhythmias (irregular heartbeats), heart failure, and blood clots leading to pulmonary emboli. The authors looked at the association of the ADT drugs with all of these CVD and found for patients on a single ADT agent there was greater than 12% chance of some adverse cardiovascular event. That went up to over 25% when the drugs were used in various combinations.
When the agents were used alone (which primarily would be the case with the LHRH agonists), the arterial vascular events were the most common ones. That was followed by arrhythmias, heart failure, then blood clots. The retrospective data analysis also confirmed that the risk of cardiovascular events was lower with the LHRH antagonist Firmagon (degarelix) rather than an LHRH agonist.
But the newer drugs had their own unique profile for CVD risk. So, for example, the second-generation antiandrogens, such as Xtandi (enzalutamide), and the potent androgen suppressor, Zytiga (abiraterone), were associated with more reports of hypertension (high blood pressure) requiring hospitalization. They also were associated with more incidence of heart failure, particularly when those agents were combined with the LHRH antagonists.
Twenty years ago, one occasionally heard prostate cancer patients being reassured, when starting on ADT, that "more men died with prostate cancer than of it". That was true then and is still true. But in retrospect we now know that it may be due in part to the adverse cardiovascular events associated with ADT.
ADT agents may extend PCa patients’ lives and reduce the risk of cancer-specific mortality. But without careful monitoring of the patients’ cardiac status and a commitment by the patients to a heart healthy lifestyle, their overall survival could be reduced by the cardiotoxic effects of the ADT drugs. The bottom line here is clear. Patients starting on ADT, whether as monotherapy or combined therapy, need medical monitoring from the cardiological perspective.
To read the study abstract, see: https://pubmed.ncbi.nlm.nih.gov/33872049/
Reference: Zhang KW, Reimers MA, Calaway AC, Fradley MG, Ponsky L, Garcia JA, Cullen J, Baumann BC, Addison D, Campbell CM, Ghosh AK, Lenihan DJ, Desai NR, Weintraub N, Guha A. Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS). J Urol. 2021 Apr 19:101097JU0000000000001785. doi: 10.1097/JU.0000000000001785. Epub ahead of print. PMID: 33872049.