Long-term ADT Found to Raise Risk of Cardiovascular Death

Long-term ADT Found to Raise Risk of Cardiovascular Death

Long-term exposure to androgen deprivation therapy (ADT), a common treatment for prostate cancer, is associated with worse cardiorespiratory fitness and a higher risk of cardiovascular death, a new study reports.

Men who received ADT therapy for more than six months were ultimately found to have a nearly four times higher risk of death than those not exposed to the therapy.

The study, “Reduced Cardiorespiratory Fitness and Increased Cardiovascular Mortality After Prolonged Androgen Deprivation Therapy for Prostate Cancer,” was published in JACC: CardioOncology.

ADT, also called hormone therapy, works by inhibiting hormonal signals that drive prostate cancer growth. The efficacy of this cancer treatment regime has been well-established. However, some studies have reported an association between exposure to ADT and a higher risk of cardiovascular death. Other research has found no such association.

Similarly, there have been conflicting reports on whether ADT impacts cardiorespiratory fitness, which is closely related to a person’s risk of cardiovascular death.

Now, researchers at the Brigham and Women’s Hospital and Dana Farber Cancer Institute, both in Boston, set out to compare cardiorespiratory fitness and cardiovascular death among prostate cancer patients who received ADT and those who did not.

Data for 616 patients followed at a single center were examined; all underwent an exercise treadmill test after their prostate cancer diagnosis. The men’s mean age was 69.6 years, and the treadmill test was performed a median of 4.8 years after their diagnosis.

Most patients (81.8%) had high cardiovascular risk, based on the presence of at least two risk factors. These factors included high blood pressure, high cholesterol, diabetes, and obesity. A large proportion of the patients were taking medication for these conditions.

In total, 150 (24.3%) of the assessed patients had received androgen deprivation therapy prior to the exercise testing. These patients were significantly older and had a higher body mass index (BMI) than those who did not get ADT. They also were more likely to have undergone radiation or chemotherapy. However, they were less likely to have had prostatectomy, or the surgical removal of the prostate.

Overall, the results showed that men who received ADT more frequently experienced reduced cardiorespiratory fitness than those who did not (48.7% vs. 32.6%). Statistically, ADT exposure significantly increased — by twofold — the likelihood of experiencing reduced fitness, and this difference remained significant after accounting for factors like age and BMI.

Among ADT-exposed patients, 99 had received it for six months or less (short exposure) and 51 for more than six months (prolonged exposure). These groups were generally similar in their demographic characteristics, cardiovascular risk factors, and medication, but only people with prolonged exposure were significantly more likely than those who did not have such treatment to have reduced cardiorespiratory fitness.

“Our findings advance the current understanding of the influence of both ADT exposure and the duration of ADT exposure on CRF [cardiorespiratory fitness],” the researchers wrote.

Over a median follow-up of 4.2 years, there were a total of 28 deaths due to cardiovascular problems. ADT therapy was associated with an increased risk of cardiovascular death; however, this difference was not statistically significant after adjusting for factors like age and BMI. Similarly, short-term exposure to the therapy was not significantly linked with a risk of cardiovascular death.

However, the risk of cardiovascular death was 3.87 times higher among those exposed to prolonged ADT, after adjusting for possible confounding variables.

“ADT use is associated with increased CV [cardiovascular] mortality, although we were able to demonstrate this association only for patients exposed to ADT for [greater than] 6 months,” the researchers concluded.

“Our finding that CV mortality risk may be a function of duration of ADT exposure might in part explain why some studies failed to demonstrate any association with CV mortality,” they added.

Longer exposure has been shown to lead to better cancer-related outcomes, but these findings suggest that such prolonged exposure also may carry safety risks that should be taken into account.

“While prolonged ADT certainly plays a role in the treatment of prostate cancer, these findings emphasize the need to consider CV surveillance/risk modification during and after ADT exposure,” John D. Groarke, study co-author and a cardiologist at Dana-Farber, said in a press release.

It is probable that multiple different biological mechanisms contribute to the effect of long-term ADT on cardiorespiratory fitness and cardiovascular death risk, the researchers said. ADT may directly impact heart, muscle, and/or bone health; it also is possible that it indirectly affects health by affecting things like sleep, depression, and pain.

The main limitations of this study are its small sample size and retrospective nature, as well as the fact that the analyzed patients had generally high cardiovascular risk – since, by design, all the patients were being referred for health-related exercise testing.

The scientists noted that further research will be necessary to determine whether cardiovascular-targeted interventions, like exercise, might help reduce cardiovascular risk in prostate cancer patients undergoing long-term ADT.

“The potential merit of exercise interventions concurrent with prolonged ADT prescription in patients with [prostate cancer] and high CV risk warrants investigation,” they concluded.