medwireNews: An analysis of the FDA Adverse Event Reporting System (FAERS) has provided detailed insight into cardiovascular adverse events (AEs) associated with different classes of androgen deprivation therapies (ADTs).
The US research team assessed the cardiovascular AE reports in the FAERS pharmacovigilance database for men with prostate cancer treated with gonadotropin releasing hormone (GnRH) agonists, GnRH antagonists, androgen receptor antagonists (ARAs), and/or androgen synthesis inhibitors between January 2000 and August 2020.
There were 6231 reports of cardiovascular AEs (12.6% of total AEs) associated with single-agent hormone therapy, while there were 1793 reports (26.1% of total AEs) associated with combination therapy, according to the article published in The Journal of Urology.
Just over half of all cardiovascular AEs with monotherapy and combination therapy were arterial vascular events, accounting for 51.9% and 56.0% of events, respectively, followed by heart failure (14.6 and 15.1%) and arrhythmias (14.4 and 16.8%).
Compared with GnRH agonists (eg, leuprolide and goserelin) as monotherapy, GnRH antagonists (eg, degarelix) were associated with significantly fewer reports of cardiovascular AEs, at a reporting odds ratio (ROR) of 0.70 after adjustment for age, reporting source, and need for hospitalization.
This was also the case for second-generation ARAs (eg, enzalutamide and apalutamide) and the androgen synthesis inhibitor abiraterone acetate, with respective RORs of 0.80 and 0.87 versus GnRH agonists, but there were significantly more reports for first-generations ARAs (eg, bicalutamide), with an ROR of 1.23.
Similarly, GnRH antagonists in any combination were associated with a significant decrease in reports of cardiovascular AEs relative to any combination therapy with a GnRH agonist (ROR=0.64). This held true for combinations of GnRH antagonists with first- and second-generation ARAs (RORs=0.45 and 0.65, respectively), but the incidence was comparable for GnRH antagonists and agonists when combined with abiraterone.
Analysis by cardiovascular event type showed that the overall reductions in reports were primarily driven by decreases in the incidence of arterial vascular events, both in the case of monotherapy and combination therapy, say Kathleen Zhang (Washington University School of Medicine, Saint Louis, Missouri) and colleagues.
But they point out that second-generation ARAs and abiraterone as single agents were associated with significantly more reports of hypertension requiring hospitalization versus GnRH agonists (RORs=1.21 and 1.19, respectively) and with more reports of heart failure when used in combination with GnRH antagonists versus agonists (RORs=2.79 and 2.57, respectively).
Noting that the FAERS database lacks “[k]ey clinical information, such as prostate cancer characteristics, duration of anti-androgen therapy, cardiovascular comorbidities, and time to the cardiovascular event,” the researchers caution that the findings are “hypothesis-generating, and do not establish causality for the reporting associations identified.”
They believe, however, that the results “highlight an important potential role for the cardiovascular community to improve overall clinical outcomes for men with prostate cancer.”
And the team concludes: “Aggressive cardiovascular risk factor modification and primary prevention therapy with aspirin and/or statins are cornerstones of therapy for patients at increased risk for arterial vascular events, with newer agents such as low-dose anticoagulants also showing clinical benefit in this setting.”
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