Certain prostate cancer treatments may increase risk for HF, MI, arrhythmias
Abiraterone and gonadotropin-releasing hormone agonists for the treatment of prostate cancer may increase the likelihood of drug-related adverse cardiac events, according to data published in EClinicalMedicine.
However, treatment for prostate cancer with enzalutamide (Xtandi, Astellas/Pfizer) was not associated with any increase in reported drug-related adverse cardiac events.
“The fact that we observed an increased cardiac risk both in patients receiving first-line androgen deprivation therapy and in patients receiving androgen receptor signaling inhibitors via abiraterone, suggest that the increased risk is at least in part due to the androgen deprivation itself, not just the coadministration of abiraterone with corticosteroids,” Eugene B. Cone, MD, urologist at Brigham and Women’s Hospital and Harvard Medical School, and colleagues wrote. “However, corticosteroids could certainly be contributing to the worsened overall cardiac risk profile, as is consistent with their association with hypertension, and could help explain the risk of HF specifically associated with abiraterone as compared to baseline androgen deprivation therapy with a gonadotropin-releasing hormone agonist.”
For this analysis, researchers utilized VigiBase, the WHO’s pharmacovigilance database, to identify cardiac adverse drug reactions in a cohort taking gonadotropin-releasing hormone (GnRH) agonists, abiraterone or enzalutamide therapy for the treatment of prostate cancer; those patients were compared with all other patients in the database.
Cardiotoxic events in prostate cancer therapies
Researchers identified 278,848 total adverse drug reactions and 2,433 cardiac-associated adverse drug reactions.
According to the study, adverse cardiac events associated with abiraterone were reported 56% more than the time-adjusted expected count based on all-other cause rates in the database; for GnRH agonists, the frequency of associated adverse cardiac events was 20% more than expected.
Researchers reported that abiraterone (reporting OR = 1.59; 95% CI, 1.48-1.71) and GnRH agonists (reporting OR = 1.21; 95% CI, 1.12-1.3) were associated with increased odds of adverse cardiac-related drug reactions.
Moreover, abiraterone was associated with higher rates of HF (reporting OR = 3.02; 95% CI, 2.6-3.51) and MI (reporting OR = 1.35; 95% CI, 1.16-1.58) and was the only drug associated with arrhythmia (reporting OR = 2.04; 95% CI, 1.82-2.3) compared with all other patients.
GnRH agonists were also associated with higher odds of HF (reporting OR = 2.06; 95% CI, 1.76-2.41) and MI (reporting OR = 1.8; 95% CI, 1.61-2.03) compared with all other patients.
Analysis of enzalutamide
Researchers observed no significant association between enzalutamide and odds for any drug-related cardiac adverse event.
“We did not find an increased reported risk of cardiac adverse drug reactions with enzalutamide, which is somewhat unexpected given that grade III or higher cardiac adverse drug reactions were reported at low rates in some trials involving the drug, although no significant differences were found in other prospective trials,” the researchers wrote. “One speculative hypothesis for the comparatively decreased odds of cardiac adverse drug reactions with enzalutamide is therefore that the higher levels of intracellular androgen are somehow cardioprotective. More work is clearly required to tease out the underlying mechanisms for the cardiac risk associated with some androgen deprivation therapy.
“Our data may preliminarily suggest that a patient with significant cardiac comorbidities may be better suited for therapy with enzalutamide over abiraterone,” the researchers wrote. “At a minimum they provide an important context for patient and provider education as to the cardiac risk associated with both traditional and newer forms of androgen deprivation therapy.”