Androgen Deprivation Therapy Could Increase Cardiovascular Risk for Prostate Cancer Patients

Use of androgen deprivation therapy as a treatment for prostate cancer was linked to a more than doubling in risk of mortality from cardiovascular causes compared to nonusers of androgen-deprivation therapy, according to the results of a new study.

In what investigators are calling the first study to assess hormone-therapy-induced cardiovascular death in a national cohort, based on real-world data, the retrospective cohort study indicates treatment with androgen deprivation therapy was associated with a more than 2-fold increase in risk of cardiovascular disease mortality, which became greater as patients aged, and also points to an association between increased risk of death from ischemic heart disease and stroke among users of androgen deprivation therapy.

“Hormone therapy is often used for patients with prostate cancer, but more research is now needed to gain a better understanding of the overall risks and benefits of this treatment,” said lead investigator Justinas Jonusas, MSc, of the Department of Radiology, Nuclear Medicine, and Medical Physics at the National Cancer Institute in Lithuania, in a statement. “Our results suggest clinicians should consider risk reduction and mitigation strategies for cardiovascular disease when developing a treatment plan for men diagnosed with prostate cancer, particularly for older patients.”

In the wake of multiple studies detailing associations between hormone therapy and increased risk of cardiovascular events, Jonusas and a team of colleagues sought to explore potential associations between use of androgen deprivation therapy and risk of cardiovascular mortality among a cohort of patients diagnosed with prostate cancer. With this in mind, investigators designed the endeavor as a retrospective cohort study of patients aged 40-79 years and diagnosed with prostate cancer between 2012-2016 within the Lithuanian Cancer registry database.

From a search of the database, investigators identified 123,343 prostate cancer patients for inclusion in their analyses. Of these, 3797 were androgen deprivation therapy users and 9546 were considered nonusers. The mean follow-up time of androgen deprivation therapy users was 4.63 years and the mean follow-up of nonusers was 5.13 years. Compared to those who were nonusers, androgen deprivation therapy users were older (67.86 vs 63.47 years). The primary outcome of interest in the investigators’ analyses was overall rate of cardiovascular death among participants. Investigators noted associations were evaluated using Cox proportional-hazards model analysis.

In unadjusted analyses, results indicated the risk of cardiovascular disease mortality was greater in the cohort of patients treated with androgen deprivation therapy than in nonusers (HR, 2.14 [95% CI, 1.86-2.45], P <.001). In analyses adjusted for stage and age groups, results indicated this increase in risk remained statistically significant (HR, 2.03 [95% CI, 1.65–2.51]; P <.001).

When assessing risk of death associated with various forms of cardiovascular disease, an increased risk of death from ischemic heart disease (HR, 1.42 [95% CI, 1.16-1.73]; P=.001); and stroke (HR, 1.70 [95% CI, 1.18-2.45]; P =.005) was observed for androgen deprivation therapy users compared to nonusers. In subgroup analyses, investigators found the risk of cardiovascular disease-related mortality was most apparent in the 70-79 years age group, which saw a nearly 5-fold increase in risk compared to nonusers (HR, 4.78 [95% CI, 3.79-6.04]; P <.001).

Investigators urged clinicians to review limitations within their study and cautioned against overinterpretation of the results. Specifically, investigators noted the study was limited by its retrospective design, a lack of information related to preexisting cardiovascular disease and risk factors, and the lower number of specific cardiovascular disease-related deaths.

“Prostate cancer is typically diagnosed in older men, over 65 years or older—and many of them will have already been diagnosed with cardiovascular disease,” Jonusas added. “It is therefore concerning that we found such a tremendous increase in the risk of cardiovascular disease-related death in elderly males receiving hormone-lowering drugs. Consequently, we would like to express our notion that this group of patients should be screened for pre-existing cardiovascular disease and their risk factors to minimize the risk of dying from these conditions.”

This study, “Androgen-deprivation therapy and risk of death from cardio-vascular disease in prostate cancer patients: a nationwide Lithuanian population-based cohort study,” was published in The Aging Male.