Androgen receptor signaling inhibitors associated with Increased cardiovascular risks ,warns study

Cardiovascular (CV) events remain a significant cause of mortality among men with advanced and metastatic prostate cancer (PCa). A recent study published in the Journal of American Medical Association highlighted the significant CV risks associated with novel androgen receptor signaling inhibitors (ARSI) that has revolutionized PCa treatment in recent years. These therapies pose marked CV toxic effects, despite their efficacy.

This comprehensive systematic review and meta-analysis quantified this risk by evaluating the incidence of CV events in men with locally advanced (M0) and metastatic (M1) PCa who received ARSI in addition to the standard of care (SOC). The study focused on randomized clinical trials involving commonly used ARSI agents including abiraterone, apalutamide, darolutamide and enzalutamide.

The research covered publications up to May 2023, through systematic searches across major databases such as PubMed, Scopus, Web of Science, EMBASE and ClinicalTrials.gov. The study included studies that reported CV events in patients with hormone-sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC), both in M0 and M1 stages.

The analysis encompassed a total of 24 studies with a combined total of 22,166 patients with a median ages ranged from 63 to 77 years. Follow-up periods varied from 3.9 to 96 months. The primary focus was on all-grade and grade 3 or higher CV events, with secondary outcomes including hypertension, acute coronary syndrome (ACS), cardiac dysrhythmia, CV death, cerebrovascular events and venous thromboembolism.

The findings found that ARSI therapy was associated with a 75% increase in the risk of all-grade CV events and more than double the risk of grade 3 or higher CV events. The specific risks for severe outcomes were markedly higher, including a 125% increase in hypertension, a 93% increase in ACS, a 64% increase in cardiac dysrhythmia, an 86% increase in cerebrovascular events and a 102% increase in CV-related deaths.

The subgroup analysis revealed that these risks were consistent across different stages and types of prostate cancer. The patients with M0 HSPC underwent a more than twofold increase in all CV events, while the individuals with M1 HSPC saw an 85% increase. Even among patients with castration-resistant prostate cancer, this risks remained significantly elevated. Overall, the outcomes of this study illuminates the necessity to inform and monitor patients regarding the potential cardiovascular risks when initiating ARSI therapy along with conventional hormonal treatments.

Reference:

El-Taji, O., Taktak, S., Jones, C., Brown, M., Clarke, N., & Sachdeva, A. (2024). Cardiovascular Events and Androgen Receptor Signaling Inhibitors in Advanced Prostate Cancer. In JAMA Oncology. American Medical Association (AMA). https://doi.org/10.1001/jamaoncol.2024.1549