Let’s start with some definitions. ARTAs and ARPIs are just two names for the same thing. The abbreviations stand for “androgen receptor targeting agents” and “androgen receptor pathway inhibitors,” respectively. The drugs go by other names as well, such as “next-generation hormonal agents”.
Right now, there are four drugs in the group: abiraterone (Zytiga, Yonsa) plus the newer anti-androgens; i.e., enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). One can expect more on the market in the next few years.
These drugs are getting a lot of attention because they have been shown to slow the progression of prostate cancer when use in combination with the standard ADT agents.
However…with more drugs come more side effects. In the case of the ARTAs, this includes some serious cardiovascular effects. Researchers have now reviewed 21 randomized control trials involving these drugs and almost 20,000 patients for data on the relative risks of various cardiovascular disease.
The results show that abiraterone and enzalutamide can lead to a significantly higher hypertension rates (high blood pressure) compared with placebo. This was not seen with apalutamide or darolutamide.
There were no significant differences between the four agents when compared to placebo for the incidence of ischemic heart disease (i.e., angina and heart attacks). The overall conclusion though is these drugs carry some increased risk of cardiotoxicity compared to placebo.
How much of a concern is this for patents? One study showed that enzalutamide is associated with a 10% increased risk of hypertension and that may be the highest cardiovascular risk in terms of percentages. But it is not necessarily the most serious as it can generally be medical managed. Heart attacks with these drugs are far less common but can be fatal and the risk of fatal cardiovascular disease goes up with unmanaged hypertension.
The authors conclude that it is “crucial to carefully monitor and manage patients treated with abiraterone or enzalutamide.” Patients offered any ARTA along with ADT should have a cardiac assessment when starting the drugs…and commit to a heart healthy lifestyle!
Reference:
Liang Zhen, Wang Juan, Feng Tianrui, Chen Yuliang, Zhou Zhien, Zhou Yi, Yan Weigang and Cao Fenghong, A net-work metaanalysis of the cardiac safety for next-generation hormonal agents in treating castration-resistant prostate cancer: how to choose drugs appropriately? Critical Reviews in Oncology / Hematology, (2024) doi: https://doi.org/10.1016/j.critrevonc.2024.104273